Journal of Functional Biomaterials

16 pages, 4996 KiB

Open AccessEditor’s ChoiceArticle

Osseointegration at Implants Installed in Composite Bone: A Randomized Clinical Trial on Sinus Floor Elevation

by Mitsuo Kotsu, Karol Alí Apaza Alccayhuaman, Mauro Ferri, Giovanna Iezzi, Adriano Piattelli, Natalia Fortich Mesa and Daniele Botticelli

J. Funct. Biomater. 2022, 13(1), 22; https://doi.org/10.3390/jfb13010022 - 28 Feb 2022

Cited by 6 | Viewed by 2818

Abstract

Osseointegration of implants installed in conjunction with sinus floor elevation might be affected by the presence of residual graft. The implant surface characteristics and the protection of the access window using a collagen membrane might influence the osseointegration. To evaluate these factors, sinus [...] Read more.

Osseointegration of implants installed in conjunction with sinus floor elevation might be affected by the presence of residual graft. The implant surface characteristics and the protection of the access window using a collagen membrane might influence the osseointegration. To evaluate these factors, sinus floor elevation was performed in patients using a natural bovine bone grafting material. The access windows were either covered with a collagen membrane made of porcine corium (Mb group) or left uncovered (No-Mb group) and, after six months, two mini-implants with either a moderate rough or turned surfaces were installed. After 3 months, biopsies containing the mini-implants were retrieved, processed histologically, and analyzed. Twenty patients, ten in each group, were included in the study. The two mini-implants were retrieved from fourteen patients, six belonging to the Mb group, and eight to the No-Mb group. No statistically significant differences were found in osseointegration between groups. However, statistically significant differences were found between the two surfaces. It was concluded that implants with a moderately rough surface installed in a composite bone presented much higher osseointegration compared to those with a turned surface. The present study failed to show an effect of the use of a collagen membrane on the access window. Full article

(This article belongs to the Special Issue Scaffolds and Implants for Bone Regeneration)

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18 pages, 28499 KiB

Open AccessEditor’s ChoiceArticle

The Comparison of Advanced Electrospun Materials Based on Poly(-3-hydroxybutyrate) with Natural and Synthetic Additives

by Polina Tyubaeva, Ivetta Varyan, Alexey Krivandin, Olga Shatalova, Svetlana Karpova, Anton Lobanov, Anatoly Olkhov and Anatoly Popov

J. Funct. Biomater. 2022, 13(1), 23; https://doi.org/10.3390/jfb13010023 - 28 Feb 2022

Cited by 7 | Viewed by 2608

Abstract

The comparison of the effect of porphyrins of natural and synthetic origin containing the same metal atom on the structure and properties of the semi-crystalline polymer matrix is of current concern. A large number of modifying additives and biodegradable polymers for biomedical purposes, [...] Read more.

The comparison of the effect of porphyrins of natural and synthetic origin containing the same metal atom on the structure and properties of the semi-crystalline polymer matrix is of current concern. A large number of modifying additives and biodegradable polymers for biomedical purposes, composed of poly(-3-hydroxybutyrate)-porphyrin, are of particular interest because of the combination of their unique properties. The objective of this work are electrospun fibrous material based on poly(-3-hydroxybutyrate) (PHB), hemin (Hmi), and tetraphenylporphyrin with iron (Fe(TPP)Cl). The structure of these new materials was investigated by methods such as optical and scanning electron microscopy, X-ray diffraction analysis, Electron paramagnetic resonance method, and Differential scanning calorimetry. The properties of the electrospun materials were analyzed by mechanical and biological tests, and the wetting contact angle was measured. In this work, it was found that even small concentrations of porphyrin can increase the antimicrobial properties by 12 times, improve the physical and mechanical properties by at least 3.5 times, and vary hydrophobicity by at least 5%. At the same time, additives similar in the structure had an oppositely directed effect on the supramolecular structure, the composition of the crystalline, and the amorphous phases. The article considers assumptions about the nature of such differences due to the influence of Hmi and Fe(TPP)Cl) on the macromolecular and fibrous structure of PHB. Full article

(This article belongs to the Special Issue Biodegradable Polymers and Textiles)

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17 pages, 5826 KiB

Open AccessEditor’s ChoiceArticle

SpAD Biofunctionalized Cellulose Acetate Scaffolds Inhibit Staphylococcus aureus Adherence in a Coordinating Function with the von Willebrand A1 Domain (vWF A1)

by Stefanos Pendas, Antonis Asiminas, Alexandros Katranidis, Costas Tsioptsias, Maria Pitou, Georgios Papadopoulos and Theodora Choli-Papadopoulou

J. Funct. Biomater. 2022, 13(1), 21; https://doi.org/10.3390/jfb13010021 - 21 Feb 2022

Cited by 2 | Viewed by 2608

Abstract

Staphylococcus aureus is one of the major pathogens causing and spreading hospital acquired infections. Since it is highly resistant to new generation antibiotics, novel strategies have to be developed such as the construction of biofunctionalized non-adherent surfaces that will prevent its tethering and [...] Read more.

Staphylococcus aureus is one of the major pathogens causing and spreading hospital acquired infections. Since it is highly resistant to new generation antibiotics, novel strategies have to be developed such as the construction of biofunctionalized non-adherent surfaces that will prevent its tethering and subsequent spread in the hospital environment. In this frame, the domain D of protein A (SpAD) of S. aureus has been immobilized onto cellulose acetate scaffolds by using the streptavidin/biotin interaction, in order to study its interaction with the A1 domain of von Willebrand factor (vWF A1), a protein essential for hemostasis, found in human plasma. Subsequently, the biofunctionalized cellulose acetate scaffolds were incubated with S. aureus in the presence and absence of vWF A1 at different time periods and their potential to inhibit S. aureus growth was studied with scanning electron microscopy (SEM). The SpAD biofunctionalized scaffolds perceptibly ameliorated the non-adherent properties of the material, and in particular, the interaction between SpAD and vWF A1 effectively inhibited the growth of S. aureus. Thus, the exhibition of significant non-adherent properties of scaffolds addresses their potential use for covering medical equipment, implants, and stents. Full article

(This article belongs to the Special Issue Cell Tissue Engineering and the Lung)

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14 pages, 3029 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Low-Modulus PMMA Has the Potential to Reduce Stresses on Endplates after Cement Discoplasty

by Susanne Lewin, Peter Försth and Cecilia Persson

J. Funct. Biomater. 2022, 13(1), 18; https://doi.org/10.3390/jfb13010018 - 4 Feb 2022

Cited by 14 | Viewed by 3621

Abstract

Cement discoplasty has been developed to treat patients with advanced intervertebral disc degeneration. In discoplasty, poly(methylmethacrylate) (PMMA) bone cement is injected into the disc, leading to reduced pain and certain spinal alignment correction. Standard PMMA-cements have much higher elastic modulus than the surrounding [...] Read more.

Cement discoplasty has been developed to treat patients with advanced intervertebral disc degeneration. In discoplasty, poly(methylmethacrylate) (PMMA) bone cement is injected into the disc, leading to reduced pain and certain spinal alignment correction. Standard PMMA-cements have much higher elastic modulus than the surrounding vertebral bone, which may lead to a propensity for adjacent fractures. A PMMA-cement with lower modulus might be biomechanically beneficial. In this study, PMMA-cements with lower modulus were obtained using previously established methods. A commercial PMMA-cement (V-steady^®, G21 srl) was used as control, and as base cement. The low-modulus PMMA-cements were modified by 12 vol% (LA12), 16 vol% (LA16) and 20 vol% (LA20) linoleic acid (LA). After storage in 37 °C PBS from 24 h up to 8 weeks, specimens were tested in compression to obtain the material properties. A lower E-modulus was obtained with increasing amount of LA. However, with storage time, the E-modulus increased. Standard and low-modulus PMMA discoplasty were compared in a previously developed and validated computational lumbar spine model. All discoplasty models showed the same trend, namely a substantial reduction in range of motion (ROM), compared to the healthy model. The V-steady model had the largest ROM-reduction (77%), and the LA20 model had the smallest (45%). The average stress at the endplate was higher for all discoplasty models than for the healthy model, but the stresses were reduced for cements with higher amounts of LA. The study indicates that low-modulus PMMA is promising for discoplasty from a mechanical viewpoint. However, validation experiments are needed, and the clinical setting needs to be further considered. Full article

(This article belongs to the Special Issue Experimentation, Numerical and Analytical Methods in Functional Biomaterials)

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12 pages, 2912 KiB

Open AccessEditor’s ChoiceArticle

Effect of Gamma Irradiation on the Osteoinductivity of Demineralized Dentin Matrix for Allografts: A Preliminary Study

by Jeong-Kui Ku, Il-hyung Kim, In-Woong Um, Bo-Hyun Kim and Pil-Young Yun

J. Funct. Biomater. 2022, 13(1), 14; https://doi.org/10.3390/jfb13010014 - 31 Jan 2022

Cited by 5 | Viewed by 3446

Abstract

Demineralized dentin matrix (DDM) treated with gamma irradiation (GR) has shown promising results as an allograft without any adverse effects in in vivo and clinical studies. The purpose of this study was to evaluate the effects of 15 and 25 kGy GR on [...] Read more.

Demineralized dentin matrix (DDM) treated with gamma irradiation (GR) has shown promising results as an allograft without any adverse effects in in vivo and clinical studies. The purpose of this study was to evaluate the effects of 15 and 25 kGy GR on the osteoinductive properties of DDM at extra-skeletal sites. As a control group, non-irradiated DDM powder was implanted into the right subcutaneous tissues of the dorsal thigh muscles of 20 nude mice. DDM powder irradiated with 15 and 25 kGy was implanted into the left side. After two and four weeks, the bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. After confirming osteoblast- and osteoclast-specific activities by alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) staining, a histological analysis was performed to measure the new bone formation and the number of osteoblasts and osteoclast-like cells on the surface of the DDMs. Histomorphometry was used to calculate the new bone formation area on the surface of the DDM particles (DDMs). The BMD in all the groups increased from two and four weeks without statistically significant differences. The osteoblasts were dominantly activated on DDM without GR, and DDM treated with 25 kGy compared to DDM treated with 15 kGy. Among the groups, new bone formation was identified in all the groups at each time point. In conclusion, GR at doses of 15 and 25 kGy does not affect the osteoinductive properties of DDM powder. Full article

(This article belongs to the Special Issue Application of Dentin Matrix in Tissue Regeneration)

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25 pages, 11491 KiB

Open AccessEditor’s ChoiceArticle

Biomimetic PLGA/Strontium-Zinc Nano Hydroxyapatite Composite Scaffolds for Bone Regeneration

by Mozan Hassan, Mohsin Sulaiman, Priya Dharshini Yuvaraju, Emmanuel Galiwango, Ihtesham ur Rehman, Ali H. Al-Marzouqi, Abbas Khaleel and Sahar Mohsin

J. Funct. Biomater. 2022, 13(1), 13; https://doi.org/10.3390/jfb13010013 - 28 Jan 2022

Cited by 25 | Viewed by 7113

Abstract

Synthetic bone graft substitutes have attracted increasing attention in tissue engineering. This study aimed to fabricate a novel, bioactive, porous scaffold that can be used as a bone substitute. Strontium and zinc doped nano-hydroxyapatite (Sr/Zn n-HAp) were synthesized by a water-based sol-gel technique. [...] Read more.

Synthetic bone graft substitutes have attracted increasing attention in tissue engineering. This study aimed to fabricate a novel, bioactive, porous scaffold that can be used as a bone substitute. Strontium and zinc doped nano-hydroxyapatite (Sr/Zn n-HAp) were synthesized by a water-based sol-gel technique. Sr/Zn n-HAp and poly (lactide-co-glycolide) (PLGA) were used to fabricate composite scaffolds by supercritical carbon dioxide technique. FTIR, XRD, TEM, SEM, and TGA were used to characterize Sr/Zn n-HAp and the composite scaffolds. The synthesized scaffolds were adequately porous with an average pore size range between 189 to 406 µm. The scaffolds demonstrated bioactive behavior by forming crystals when immersed in the simulated body fluid. The scaffolds after immersing in Tris/HCl buffer increased the pH value of the medium, establishing their favorable biodegradable behavior. ICP-MS study for the scaffolds detected the presence of Sr, Ca, and Zn ions in the SBF within the first week, which would augment osseointegration if implanted in the body. nHAp and their composites (PLGA-nHAp) showed ultimate compressive strength ranging between 0.4–19.8 MPa. A 2.5% Sr/Zn substituted nHAp-PLGA composite showed a compressive behavior resembling that of cancellous bone indicating it as a good candidate for cancellous bone substitute. Full article

(This article belongs to the Special Issue Smart Biomaterials for Soft and Hard Tissue Repair and Regeneration)

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11 pages, 3070 KiB

Open AccessEditor’s ChoiceArticle

Preliminary Results on Heparin-Modified Double-Layered PCL and PLA-Based Scaffolds for Tissue Engineering of Small Blood Vessels

by Patrycja Domalik-Pyzik and Anna Morawska-Chochół

J. Funct. Biomater. 2022, 13(1), 11; https://doi.org/10.3390/jfb13010011 - 27 Jan 2022

Cited by 3 | Viewed by 3015

Abstract

Low-diameter blood vessels are challenging to replace with more traditional synthetic vascular grafts. Therefore, the obvious choice is to try to regenerate small veins and arteries through tissue-engineering approaches. However, the layered structure of native vessels and blood compatibility issues make this a [...] Read more.

Low-diameter blood vessels are challenging to replace with more traditional synthetic vascular grafts. Therefore, the obvious choice is to try to regenerate small veins and arteries through tissue-engineering approaches. However, the layered structure of native vessels and blood compatibility issues make this a very challenging task. The aim of this study is to create double-layered tubular scaffolds with enhanced anticoagulant properties for the tissue engineering of small blood vessels. The scaffolds were made of a polycaprolactone-based porous outer layer and a polylactide-based electrospun inner layer modified with heparin. The combination of thermally induced phase separation and electrospinning resulted in asymmetric scaffolds with improved mechanical properties. The release assay confirmed that heparin is released from the scaffolds. Additionally, anticoagulant activity was shown through APTT (activated partial thromboplastin time) assay. Interestingly, the endothelial cell culture test revealed that after 14 days of culture, HAECs (human aortic endothelial cell lines) tended to organize in chain-like structures, typical for early stages of vascular formation. In the longer culture, HAEC viability was higher for the heparin-modified scaffolds. The proposed scaffold design and composition have great potential for application in tissue engineering of small blood vessels. Full article

(This article belongs to the Special Issue Bioinspired Materials for Medical and Biotechnological Applications)

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11 pages, 8011 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

3D Printing of Hierarchically Porous Lattice Structures Based on Åkermanite Glass Microspheres and Reactive Silicone Binder

by Arish Dasan, Jozef Kraxner, Luca Grigolato, Gianpaolo Savio, Hamada Elsayed, Dušan Galusek and Enrico Bernardo

J. Funct. Biomater. 2022, 13(1), 8; https://doi.org/10.3390/jfb13010008 - 13 Jan 2022

Cited by 9 | Viewed by 3897

Abstract

The present study illustrates the manufacturing method of hierarchically porous 3D scaffolds based on åkermanite as a promising bioceramic for stereolithography. The macroporosity was designed by implementing 3D models corresponding to different lattice structures (cubic, diamond, Kelvin, and Kagome). To obtain micro-scale porosity, [...] Read more.

The present study illustrates the manufacturing method of hierarchically porous 3D scaffolds based on åkermanite as a promising bioceramic for stereolithography. The macroporosity was designed by implementing 3D models corresponding to different lattice structures (cubic, diamond, Kelvin, and Kagome). To obtain micro-scale porosity, flame synthesized glass microbeads with 10 wt% of silicone resins were utilized to fabricate green scaffolds, later converted into targeted bioceramic phase by firing at 1100 °C in air. No chemical reaction between the glass microspheres, crystallizing into åkermanite, and silica deriving from silicone oxidation was observed upon heat treatment. Silica acted as a binder between the adjacent microspheres, enhancing the creation of microporosity, as documented by XRD, and SEM coupled with EDX analysis. The formation of ‘spongy’ struts was confirmed by infiltration with Rhodamine B solution. The compressive strength of the sintered porous scaffolds was up to 0.7 MPa with the porosity of 68–84%. Full article

(This article belongs to the Special Issue Bioceramics and Bioactive Glass-Based Materials)

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20 pages, 5113 KiB

Open AccessEditor’s ChoiceArticle

Surface Functionalization of Poly(l-lactide-co-glycolide) Membranes with RGD-Grafted Poly(2-oxazoline) for Periodontal Tissue Engineering

by Anna M. Tryba, Małgorzata Krok-Borkowicz, Michał Kula, Natalia Piergies, Mateusz Marzec, Erik Wegener, Justyna Frączyk, Rainer Jordan, Beata Kolesińska, Dieter Scharnweber, Czesława Paluszkiewicz and Elżbieta Pamuła

J. Funct. Biomater. 2022, 13(1), 4; https://doi.org/10.3390/jfb13010004 - 7 Jan 2022

Cited by 13 | Viewed by 3803

Abstract

Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(l [...] Read more.

Bone tissue defects resulting from periodontal disease are often treated using guided tissue regeneration (GTR). The barrier membranes utilized here should prevent soft tissue infiltration into the bony defect and simultaneously support bone regeneration. In this study, we designed a degradable poly(l-lactide-co-glycolide) (PLGA) membrane that was surface-modified with cell adhesive arginine-glycine-aspartic acid (RGD) motifs. For a novel method of membrane manufacture, the RGD motifs were coupled with the non-ionic amphiphilic polymer poly(2-oxazoline) (POx). The RGD-containing membranes were then prepared by solvent casting of PLGA, POx coupled with RGD (POx_RGD), and poly(ethylene glycol) (PEG) solution in methylene chloride (DCM), followed by DCM evaporation and PEG leaching. Successful coupling of RGD to POx was confirmed spectroscopically by Raman, Fourier transform infrared in attenuated reflection mode (FTIR-ATR), and X-ray photoelectron (XPS) spectroscopy, while successful immobilization of POx_RGD on the membrane surface was confirmed by XPS and FTIR-ATR. The resulting membranes had an asymmetric microstructure, as shown by scanning electron microscopy (SEM), where the glass-cured surface was more porous and had a higher surface area then the air-cured surface. The higher porosity should support bone tissue regeneration, while the air-cured side is more suited to preventing soft tissue infiltration. The behavior of osteoblast-like cells on PLGA membranes modified with POx_RGD was compared to cell behavior on PLGA foil, non-modified PLGA membranes, or PLGA membranes modified only with POx. For this, MG-63 cells were cultured for 4, 24, and 96 h on the membranes and analyzed by metabolic activity tests, live/dead staining, and fluorescent staining of actin fibers. The results showed bone cell adhesion, proliferation, and viability to be the highest on membranes modified with POx_RGD, making them possible candidates for GTR applications in periodontology and in bone tissue engineering. Full article

(This article belongs to the Special Issue Bioinspired Materials for Medical and Biotechnological Applications)

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20 pages, 1529 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Properties and Applications of PDMS for Biomedical Engineering: A Review

by Inês Miranda, Andrews Souza, Paulo Sousa, João Ribeiro, Elisabete M. S. Castanheira, Rui Lima and Graça Minas

J. Funct. Biomater. 2022, 13(1), 2; https://doi.org/10.3390/jfb13010002 - 21 Dec 2021

Cited by 302 | Viewed by 21338

Abstract

Polydimethylsiloxane (PDMS) is an elastomer with excellent optical, electrical and mechanical properties, which makes it well-suited for several engineering applications. Due to its biocompatibility, PDMS is widely used for biomedical purposes. This widespread use has also led to the massification of the soft-lithography [...] Read more.

Polydimethylsiloxane (PDMS) is an elastomer with excellent optical, electrical and mechanical properties, which makes it well-suited for several engineering applications. Due to its biocompatibility, PDMS is widely used for biomedical purposes. This widespread use has also led to the massification of the soft-lithography technique, introduced for facilitating the rapid prototyping of micro and nanostructures using elastomeric materials, most notably PDMS. This technique has allowed advances in microfluidic, electronic and biomedical fields. In this review, an overview of the properties of PDMS and some of its commonly used treatments, aiming at the suitability to those fields’ needs, are presented. Applications such as microchips in the biomedical field, replication of cardiovascular flow and medical implants are also reviewed. Full article

(This article belongs to the Special Issue Medical Application of Functional Biomaterials)

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12 pages, 2130 KiB

Open AccessEditor’s ChoiceArticle

Design of Asymmetric Nanofibers-Membranes Based on Polyvinyl Alcohol and Wool-Keratin for Wound Healing Applications

by Diego O. Sanchez Ramirez, Iriczalli Cruz-Maya, Claudia Vineis, Cinzia Tonetti, Alessio Varesano and Vincenzo Guarino

J. Funct. Biomater. 2021, 12(4), 76; https://doi.org/10.3390/jfb12040076 - 20 Dec 2021

Cited by 25 | Viewed by 4221

Abstract

The development of asymmetric membranes—i.e., matching two fibrous layers with selected composition and morphological properties to mimic both the epidermis and dermis—currently represents one of the most promising strategies to support skin regeneration during the wound healing process. Herein, a new asymmetric platform [...] Read more.

The development of asymmetric membranes—i.e., matching two fibrous layers with selected composition and morphological properties to mimic both the epidermis and dermis—currently represents one of the most promising strategies to support skin regeneration during the wound healing process. Herein, a new asymmetric platform fabricated by a sequential electrospinning process was investigated. The top layer comprises cross-linked polyvinylalcohol (PVA) nanofibers (NFs)—from water solution—to replicate the epidermis’s chemical stability and wettability features. Otherwise, the bottom layer is fabricated by integrating PVA with wool-keratin extracted via sulfitolysis. This protein is a biocompatibility polymer with excellent properties for dermis-like structures. Morphological characterization via SEM supported by image analysis showed that the asymmetric membrane exhibited average fiber size—max frequency diameter 450 nm, range 1.40 μm—and porosity suitable for the healing process. FTIR-spectrums confirmed the presence of keratin in the bottom layer and variations of keratin-secondary structures. Compared with pure PVA-NFs, keratin/PVA-NFs showed a significant improvement in cell adhesion in in vitro tests. In perspective, these asymmetric membranes could be promisingly used to confine active species (i.e., antioxidants, antimicrobials) to the bottom layer to support specific cell activities (i.e., proliferation, differentiation) in wound healing applications. Full article

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25 pages, 10331 KiB

Open AccessEditor’s ChoiceArticle

Functionalized Nanocellulose Drives Neural Stem Cells toward Neuronal Differentiation

by Sahitya Chetan Pandanaboina, Ambar B. RanguMagar, Krishna D. Sharma, Bijay P. Chhetri, Charlette M. Parnell, Jennifer Yanhua Xie, Malathi Srivatsan and Anindya Ghosh

J. Funct. Biomater. 2021, 12(4), 64; https://doi.org/10.3390/jfb12040064 - 22 Nov 2021

Cited by 4 | Viewed by 3732

Abstract

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population [...] Read more.

Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC–Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC–Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC–Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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15 pages, 3221 KiB

Open AccessEditor’s ChoiceArticle

Preparation and Characterization of Moldable Demineralized Bone Matrix/Calcium Sulfate Composite Bone Graft Materials

by I-Cheng Chen, Chen-Ying Su, Chun-Cheih Lai, Yi-Syue Tsou, Yudong Zheng and Hsu-Wei Fang

J. Funct. Biomater. 2021, 12(4), 56; https://doi.org/10.3390/jfb12040056 - 4 Oct 2021

Cited by 19 | Viewed by 6309

Abstract

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO₄, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, [...] Read more.

Demineralized bone matrix (DBM) is a decalcified allo/xenograft retaining collagen and noncollagenous proteins, which has been extensively used because of its osteoconductive and osteoinductive properties. Calcium sulfate (CaSO₄, CS) is a synthetic bone substitute used in bone healing with biocompatible, nontoxic, bioabsorbable, osteoconductive, and good mechanical characteristics. This study aims to prepare a DBM/CS composite bone graft material in a moldable putty form without compromising the peculiar properties of DBM and CS. For this purpose, firstly, porcine femur was defatted using chloroform/methanol and extracted by acid for demineralization, then freeze-dried and milled/sieved to obtain DBM powder. Secondly, the α-form and β-form of calcium sulfate hemihydrate (CaSO₄·0.5H₂O, CSH) were produced by heating gypsum (CaSO₄·2H₂O). The morphology and particle sizes of α- and β-CSH were obtained by SEM, and their chemical properties were confirmed by EDS, FTIR and XRD. Furthermore, the DBM-based graft was mixed with α- or β-CSH at a ratio of 9:1, and glycerol/4% HPMC was added as a carrier to produce a putty. DBM/CSH putty possesses a low washout rate, good mechanical strength and biocompatibility. In conclusion, we believe that the moldable DBM/CSH composite putty developed in this study could be a promising substitute for the currently available bone grafts, and might have practical application in the orthopedics field as a potential bone void filler. Full article

(This article belongs to the Special Issue Bioceramics and Bioactive Glass-Based Materials)

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12 pages, 3215 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Corrosion of SiC-Coated Anodized Ti Nano-Tubular Surfaces

by Shu-Min Hsu, Chaker Fares, Xinyi Xia, Md Abu Jafar Rasel, Jacob Ketter, Samira Esteves Afonso Camargo, Md Amanul Haque, Fan Ren and Josephine F. Esquivel-Upshaw

J. Funct. Biomater. 2021, 12(3), 52; https://doi.org/10.3390/jfb12030052 - 16 Sep 2021

Cited by 5 | Viewed by 3493

Abstract

Peri-implantitis leads to implant failure and decreases long-term survival and success rates of implant-supported prostheses. The pathogenesis of this disease is complex but implant corrosion is believed to be one of the many factors which contributes to progression of this disease. A nanostructured [...] Read more.

Peri-implantitis leads to implant failure and decreases long-term survival and success rates of implant-supported prostheses. The pathogenesis of this disease is complex but implant corrosion is believed to be one of the many factors which contributes to progression of this disease. A nanostructured titanium dioxide layer was introduced using anodization to improve the functionality of dental implants. In the present study, we evaluated the corrosion performance of silicon carbide (SiC) on anodized titanium dioxide nanotubes (ATO) using plasma-enhanced chemical vapor deposition (PECVD). This was investigated through a potentiodynamic polarization test and bacterial incubation for 30 days. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze surface morphologies of non-coated and SiC-coated nanotubes. Energy dispersive X-ray (EDX) was used to analyze the surface composition. In conclusion, SiC-coated ATO exhibited improved corrosion resistance and holds promise as an implant coating material. Full article

(This article belongs to the Special Issue Nanoengineered Materials for Biomedical Applications)

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16 pages, 1176 KiB

Open AccessEditor’s ChoiceReview

Effect of Resin Infiltration on Enamel: A Systematic Review and Meta-Analysis

by Madalena Soveral, Vanessa Machado, João Botelho, José João Mendes and Cristina Manso

J. Funct. Biomater. 2021, 12(3), 48; https://doi.org/10.3390/jfb12030048 - 16 Aug 2021

Cited by 24 | Viewed by 6007

Abstract

Subsurface enamel demineralization beneath an intact surface layer or white spots lesions (WSL) can and should be treated with non-invasive procedures to impede the development of a cavitated lesion. We aim to analyze if infiltrative resin improves enamel roughness, microhardness, shear bond strength, [...] Read more.

Subsurface enamel demineralization beneath an intact surface layer or white spots lesions (WSL) can and should be treated with non-invasive procedures to impede the development of a cavitated lesion. We aim to analyze if infiltrative resin improves enamel roughness, microhardness, shear bond strength, and penetration depth. MEDLINE [via Pubmed], Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scholar, and LILACS were searched until May 2021. Methodological quality was assessed using the Joanna Briggs Institute Clinical Appraisal Checklist for Experimental Studies. Pairwise ratio of means (ROM) meta-analyses were carried out to compare the enamel properties after treatment with infiltrative resin on sound enamel and WSLs. From a total of 1604 articles, 48 studies were included. Enamel surface roughness decreased 35% in sound enamel (95%CI: 0.49–0.85, I² = 98.2%) and 54% in WSLs (95%CI: 0.29–0.74, I² = 98.5%). Microhardness reduced 24% in sound enamel (95%CI: 0.73–0.80, I² = 99.1%) and increased by 68% in WSLs (95%CI: 1.51; 1.86, I² = 99.8%). Shear bond strength reduced of 25% in sound enamel (95%CI: 0.60; 0.95, I² = 96.9%) and increased by 89% in WSLs (95%CI: 1.28–2.79, I² = 99.8%). Penetration depth was 65.39% of the WSLs (95%CI: 56.11–74.66, I² = 100%). Infiltrative resins effectively promote evident changes in enamel properties in sound and WSLs. Future studies with long-term follow-ups are necessary to corroborate these results from experimental studies. Full article

(This article belongs to the Special Issue Recent Advances in Dental Implants and Biomaterials)

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16 pages, 4792 KiB

Open AccessEditor’s ChoiceArticle

Bioprinting and In Vitro Characterization of an Eggwhite-Based Cell-Laden Patch for Endothelialized Tissue Engineering Applications

by Yasaman Delkash, Maxence Gouin, Tanguy Rimbeault, Fatemeh Mohabatpour, Petros Papagerakis, Sean Maw and Xiongbiao Chen

J. Funct. Biomater. 2021, 12(3), 45; https://doi.org/10.3390/jfb12030045 - 11 Aug 2021

Cited by 20 | Viewed by 4884

Abstract

Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural [...] Read more.

Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural bioink from chicken eggwhite and sodium alginate for bioprinting cell-laden patches to be used in endothelialized tissue engineering applications. Eggwhite was utilized for enhanced biological properties, while sodium alginate was used to improve bioink printability. The rheological properties of bioinks with varying amounts of sodium alginate were examined with the results illustrating that 2.0–3.0% (w/v) sodium alginate was suitable for printing patch constructs. The printed patches were then characterized mechanically and biologically, and the results showed that the printed patches exhibited elastic moduli close to that of natural heart tissue (20–27 kPa) and more than 94% of the vascular endothelial cells survived in the examination period of one week post 3D bioprinting. Our research also illustrated the printed patches appropriate water uptake ability (>1800%). Full article

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20 pages, 3102 KiB

Open AccessEditor’s ChoiceArticle

Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model

by Leyla Hasandoost, Daniella Marx, Paul Zalzal, Oleg Safir, Mark Hurtig, Cina Mehrvar, Stephen D. Waldman, Marcello Papini and Mark R. Towler

J. Funct. Biomater. 2021, 12(3), 44; https://doi.org/10.3390/jfb12030044 - 5 Aug 2021

Cited by 2 | Viewed by 2955

Abstract

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. [...] Read more.

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO₂-CaO-SrO-P₂O₅-Ta₂O₅, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone–cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn²⁺ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone. Full article

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12 pages, 1839 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Finite Element Method for the Evaluation of the Human Spine: A Literature Overview

by Symeon Naoum, Angelo V. Vasiliadis, Christos Koutserimpas, Nikolaos Mylonakis, Michail Kotsapas and Konstantinos Katakalos

J. Funct. Biomater. 2021, 12(3), 43; https://doi.org/10.3390/jfb12030043 - 31 Jul 2021

Cited by 33 | Viewed by 5851

Abstract

The finite element method (FEM) represents a computer simulation method, originally used in civil engineering, which dates back to the early 1940s. Applications of FEM have also been used in numerous medical areas and in orthopedic surgery. Computing technology has improved over the [...] Read more.

The finite element method (FEM) represents a computer simulation method, originally used in civil engineering, which dates back to the early 1940s. Applications of FEM have also been used in numerous medical areas and in orthopedic surgery. Computing technology has improved over the years and as a result, more complex problems, such as those involving the spine, can be analyzed. The spine is a complex anatomical structure that maintains the erect posture and supports considerable loads. Applications of FEM in the spine have contributed to the understanding of bone biomechanics, both in healthy and abnormal conditions, such as scoliosis, fractures (trauma), degenerative disc disease and osteoporosis. However, since FEM is only a digital simulation of the real condition, it will never exactly simulate in vivo results. In particular, when it concerns biomechanics, there are many features that are difficult to represent in a FEM. More FEM studies and spine research are required in order to examine interpersonal spine stiffness, young spine biomechanics and model accuracy. In the future, patient-specific models will be used for better patient evaluations as well as for better pre- and inter-operative planning. Full article

(This article belongs to the Special Issue Experimentation, Numerical and Analytical Methods in Functional Biomaterials)

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15 pages, 2700 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Biomaterials for Cell-Surface Engineering and Their Efficacy

by Seoyoung Jang, Jin Gil Jeong, Tong In Oh and EunAh Lee

J. Funct. Biomater. 2021, 12(3), 41; https://doi.org/10.3390/jfb12030041 - 13 Jul 2021

Cited by 4 | Viewed by 3298

Abstract

Literature in the field of stem cell therapy indicates that, when stem cells in a state of single-cell suspension are injected systemically, they show poor in vivo survival, while such cells show robust cell survival and regeneration activity when transplanted in the state [...] Read more.

Literature in the field of stem cell therapy indicates that, when stem cells in a state of single-cell suspension are injected systemically, they show poor in vivo survival, while such cells show robust cell survival and regeneration activity when transplanted in the state of being attached on a biomaterial surface. Although an attachment-deprived state induces anoikis, when cell-surface engineering technology was adopted for stem cells in a single-cell suspension state, cell survival and regenerative activity dramatically improved. The biochemical signal coming from ECM (extracellular matrix) molecules activates the cell survival signal transduction pathway and prevents anoikis. According to the target disease, various therapeutic cells can be engineered to improve their survival and regenerative activity, and there are several types of biomaterials available for cell-surface engineering. In this review, biomaterial types and application strategies for cell-surface engineering are presented along with their expected efficacy. Full article

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17 pages, 1626 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Electrical Stimulation to Enhance Wound Healing

by Saranya B. Rajendran, Kirsty Challen, Karen L. Wright and John G. Hardy

J. Funct. Biomater. 2021, 12(2), 40; https://doi.org/10.3390/jfb12020040 - 19 Jun 2021

Cited by 51 | Viewed by 19069

Abstract

Electrical stimulation (ES) can serve as a therapeutic modality accelerating the healing of wounds, particularly chronic wounds which have impaired healing due to complications from underlying pathology. This review explores how ES affects the cellular mechanisms of wound healing, and its effectiveness in [...] Read more.

Electrical stimulation (ES) can serve as a therapeutic modality accelerating the healing of wounds, particularly chronic wounds which have impaired healing due to complications from underlying pathology. This review explores how ES affects the cellular mechanisms of wound healing, and its effectiveness in treating acute and chronic wounds. Literature searches with no publication date restrictions were conducted using the Cochrane Library, Medline, Web of Science, Google Scholar and PubMed databases, and 30 full-text articles met the inclusion criteria. In vitro and in vivo experiments investigating the effect of ES on the general mechanisms of healing demonstrated increased epithelialization, fibroblast migration, and vascularity around wounds. Six in vitro studies demonstrated bactericidal effects upon exposure to alternating and pulsed current. Twelve randomized controlled trials (RCTs) investigated the effect of pulsed current on chronic wound healing. All reviewed RCTs demonstrated a larger reduction in wound size and increased healing rate when compared to control groups. In conclusion, ES therapy can contribute to improved chronic wound healing and potentially reduce the financial burden associated with wound management. However, the variations in the wound characteristics, patient demographics, and ES parameters used across studies present opportunities for systematic RCT studies in the future. Full article

(This article belongs to the Special Issue Biotechnological Approaches and Biomaterials for Enhanced Wound Healing)

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17 pages, 7753 KiB

Open AccessEditor’s ChoiceArticle

Physico-Chemical Properties and Biocompatibility of Thermosensitive Chitosan Lactate and Chitosan Chloride Hydrogels Developed for Tissue Engineering Application

by Katarzyna Pieklarz, Grzegorz Galita, Michał Tylman, Waldemar Maniukiewicz, Ewa Kucharska, Ireneusz Majsterek and Zofia Modrzejewska

J. Funct. Biomater. 2021, 12(2), 37; https://doi.org/10.3390/jfb12020037 - 20 May 2021

Cited by 18 | Viewed by 4376

Abstract

Recently, the modification of the initial structure of biopolymers, mainly chitosan, has been gaining importance with a view to obtain functional forms with increased practicality and specific properties enabling their use in tissue engineering. Therefore, in this article, the properties (structural and biological) [...] Read more.

Recently, the modification of the initial structure of biopolymers, mainly chitosan, has been gaining importance with a view to obtain functional forms with increased practicality and specific properties enabling their use in tissue engineering. Therefore, in this article, the properties (structural and biological) of thermosensitive hydrogels obtained from chitosan lactate/chloride and two types of crosslinking agents (β-glycerol phosphate disodium salt pentahydrate and uridine 5′-monophosphate disodium salt) are discussed. The aim of the research is to identify changes in the structure of the biomaterials during conditioning in water. Structural investigations were carried out by FTIR spectroscopy. The crystallinity of gels was determined by X-ray diffraction analysis. The biocompatibility (evaluation of cytotoxicity and genotoxicity) of chitosan hydrogels was investigated by contact with human colon adenocarcinoma cell line for 48 h. The cytotoxicity was verified based on the colorimetric resazurin assay, and the genotoxicity was checked by the comet assay (percentage of DNA in the comet tail). The conducted research showed that the analyzed types of chitosan hydrogels are non-cytotoxic and non-genotoxic materials. The good biocompatibility of chitosan hydrogels surfaces makes them interesting scaffolds with clinical potential in tissue regeneration engineering. Full article

(This article belongs to the Special Issue Bioinspired Materials for Medical and Biotechnological Applications)

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15 pages, 1928 KiB

Open AccessEditor’s ChoiceArticle

TiAl6V4 Alloy Surface Modifications and Their Impact on Biofilm Development of S. aureus and S. epidermidis

by Astrid H. Paulitsch-Fuchs, Lukas Wolrab, Nicole Eck, Nigel P. Dyer, Benjamin Bödendorfer and Birgit Lohberger

J. Funct. Biomater. 2021, 12(2), 36; https://doi.org/10.3390/jfb12020036 - 18 May 2021

Cited by 7 | Viewed by 3328

Abstract

One of the most serious complications following joint replacement surgeries are periprosthetic infections (PIs) arising from the adhesion of bacteria to the artificial joint. Various types of titanium–aluminum–vanadium (TiAl6V4) alloy surface modifications (coatings with silver (Ag), titanium nitride (TiN), pure titanium (cpTi), combinations [...] Read more.

One of the most serious complications following joint replacement surgeries are periprosthetic infections (PIs) arising from the adhesion of bacteria to the artificial joint. Various types of titanium–aluminum–vanadium (TiAl6V4) alloy surface modifications (coatings with silver (Ag), titanium nitride (TiN), pure titanium (cpTi), combinations of cpTi and hydroxyapatite (HA), combinations of cpTi and tricalcium phosphate (TCP), and a rough-blasted surface of TiAl6V4) have been investigated to assess their effects on biofilm development. Biofilms were grown, collected, and analyzed after 48 h to measure their protein and glucose content and the cell viability. Biofilm-associated genes were also monitored after 48 h of development. There was a distinct difference in the development of staphylococcal biofilms on the surfaces of the different types of alloy. According to the findings of this study, the base alloy TiAl6V4 and the TiN-coated surface are the most promising materials for biofilm reduction. Rough surfaces are most favorable when it comes to bacterial infections because they allow an easy attachment of pathogenic organisms. Of all rough surfaces tested, rough-blasted TiAl6V4 was the most favorable as an implantation material; all the other rough surfaces showed more distinct signs of inducing the development of biofilms which displayed higher protein and polysaccharide contents. These results are supported by RT-qPCR measurements of biofilm associated genes for Staphylococcus aureus (icaA, icaC, fnbA, fnbB, clfB, atl) and Staphylococcus epidermidis (atle, aap). Full article

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8 pages, 1215 KiB

Open AccessEditor’s ChoiceArticle

Aesthetic Outcomes and Peri-Implant Health of Angled Screw Retained Implant Restorations Compared with Cement Retained Crowns: Medium Term Follow-Up

by Livia Nastri, Ludovica Nucci, Vincenzo Grassia and Rino Miraldi

J. Funct. Biomater. 2021, 12(2), 35; https://doi.org/10.3390/jfb12020035 - 16 May 2021

Cited by 8 | Viewed by 3327

Abstract

Single tooth implant restorations in the aesthetic area are a demanding challenge. If a complete osseointegration is mandatory, the final result has to result in a higher standard of biomimetic and soft tissue health among natural teeth. This outcome is traditionally pursued by [...] Read more.

Single tooth implant restorations in the aesthetic area are a demanding challenge. If a complete osseointegration is mandatory, the final result has to result in a higher standard of biomimetic and soft tissue health among natural teeth. This outcome is traditionally pursued by cementing crowns over individualized abutments. However, in recent years, the need for controlling peri-implant health and the preference towards a retrievable solution has led to an increase in screw-retained crowns, which is not always applicable when the implant axis is not ideal. In the aesthetic area, the use of a novel technical solution represented by the angled screw channel (ASC) of the abutment has been proposed in order to match the advantages of the screwed solution with the aesthetic demands. The aim of this study was to compare ASC crowns to cemented crowns (CC) in single implant restorations using the white esthetic score (WES) and pink esthetic score (PES) at the crown delivery and at a follow-up of a minimum of 2 years. Peri-implant health and marginal bone loss (MBL) were also evaluated. The mean follow-up was 44.3 months, with a mean MBL of 0.22 mm in the ASC group and 0.29 mm in the CC group. The total WES/PES score was 16.6 for ASC, compared with 17.3 for CC at baseline, and 16.2 and 17.1, respectively, at follow-up. Both of the groups reached a high WES/PES, and this was maintained over time, without signs of peri-implant diseases or bone loss, regardless of the choice of connection. In conclusion, ASC can be adopted in cases where the implant axis is not ideal, with aesthetic and functional results that are comparable to implants restored by cemented crowns. Full article

(This article belongs to the Special Issue Advanced Functional Biomaterials for Dental Implants)

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18 pages, 1916 KiB

Open AccessEditor’s ChoiceArticle

EtoGel for Intra-Articular Drug Delivery: A New Challenge for Joint Diseases Treatment

by Maria Chiara Cristiano, Antonia Mancuso, Elena Giuliano, Donato Cosco, Donatella Paolino and Massimo Fresta

J. Funct. Biomater. 2021, 12(2), 34; https://doi.org/10.3390/jfb12020034 - 16 May 2021

Cited by 18 | Viewed by 3200

Abstract

Ethosomes^® have been proposed as potential intra-articular drug delivery devices, in order to obtain a longer residence time of the delivered drug in the knee joint. To this aim, the conventional composition and preparation method were modified. Ethosomes^® were prepared by [...] Read more.

Ethosomes^® have been proposed as potential intra-articular drug delivery devices, in order to obtain a longer residence time of the delivered drug in the knee joint. To this aim, the conventional composition and preparation method were modified. Ethosomes^® were prepared by using a low ethanol concentration and carrying out a vesicle extrusion during the preparation. The modified composition did not affect the deformability of ethosomes^®, a typical feature of this colloidal vesicular topical carrier. The maintenance of sufficient deformability bodes well for an effective ethosome^® application in the treatment of joint pathologies because they should be able to go beyond the pores of the dense collagen II network. The investigated ethosomes^® were inserted in a three-dimensional network of thermo-sensitive poloxamer gel (EtoGel) to improve the residence time in the joint. Rheological experiments evidenced that EtoGel could allow an easy intra-articular injection at room temperature and hence transform itself in gel form at body temperature into the joint. Furthermore, EtoGel seemed to be able to support the knee joint during walking and running. In vitro studies demonstrated that the amount of used ethanol did not affect the viability of human chondrocytes and nanocarriers were also able to suitably interact with cells. Full article

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10 pages, 6210 KiB

Open AccessEditor’s ChoiceArticle

Endothelial Cell Responses to a Highly Deformable Titanium Alloy Designed for Vascular Stent Applications

by Raluca Ion, Gaëtan Cabon, Doina-Margareta Gordin, Elena Ionica, Thierry Gloriant and Anisoara Cimpean

J. Funct. Biomater. 2021, 12(2), 33; https://doi.org/10.3390/jfb12020033 - 14 May 2021

Cited by 6 | Viewed by 2704

Abstract

Titanium alloys are widely used for biomedical applications due to their good biocompatibility. Nevertheless, they cannot be used for balloon expandable stents due to a lack of ductility compared to cobalt-chromium (Co-Cr) alloys and stainless steels. In this study, a new highly deformable [...] Read more.

Titanium alloys are widely used for biomedical applications due to their good biocompatibility. Nevertheless, they cannot be used for balloon expandable stents due to a lack of ductility compared to cobalt-chromium (Co-Cr) alloys and stainless steels. In this study, a new highly deformable Ti-16Nb-8Mo alloy was designed for such an application. However, the biological performance of a stent material is strongly influenced by the effect exerted on the behavior of endothelial cells. Therefore, the cellular responses of human umbilical vein endothelial cells (HUVECs), including morphological characteristics, cell viability and proliferation, and functional markers expression, were investigated to evaluate the biocompatibility of the alloy in the present study. The in vitro results demonstrated the suitability of this alloy for use as endovascular stents. Full article

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27 pages, 5289 KiB

Open AccessEditor’s ChoiceArticle

Functionalization with a Polyphenol-Rich Pomace Extract Empowers a Ceramic Bone Filler with In Vitro Antioxidant, Anti-Inflammatory, and Pro-Osteogenic Properties

by Giorgio Iviglia, Elisa Torre, Clara Cassinelli and Marco Morra

J. Funct. Biomater. 2021, 12(2), 31; https://doi.org/10.3390/jfb12020031 - 5 May 2021

Cited by 7 | Viewed by 3112

Abstract

Oral diseases and periodontitis in particular are a major health burden worldwide, because of their association with various systemic diseases and with conditions such as peri-implantitis. Attempts have been made over the years to reverse bone loss due to the host disproportionate inflammatory [...] Read more.

Oral diseases and periodontitis in particular are a major health burden worldwide, because of their association with various systemic diseases and with conditions such as peri-implantitis. Attempts have been made over the years to reverse bone loss due to the host disproportionate inflammatory response and to prevent failure of dental implants. To this end, the use of biomaterials functionalized with molecules characterized by anti-inflammatory and antioxidant properties could represent a new frontier for regenerating functional periodontal tissues. In this study, a new ceramic granulated biomaterial, named Synergoss Red (SR), functionalized with a polyphenolic mixture extracted from pomace of the Croatina grape variety, is introduced. Following a preliminary in-depth characterization of the extract by HPLC analysis and of the biomaterial surface and composition, we performed evaluations of cytocompatibility and a biological response through in vitro assays. The anti-inflammatory and antioxidant properties of the identified phenolic molecules contained in SR were shown to downregulate inflammation in macrophages, to stimulate in osteoblast-like cells the expression of genes involved in deposition of the early bone matrix, and to mitigate bone remodeling by decreasing the RANKL/OPG ratio. Thanks to its cytocompatibility and assorted beneficial effects on bone regeneration, SR could be considered an innovative regenerative approach in periodontal therapy. Full article

(This article belongs to the Special Issue Recent Advances in Dental Implants and Biomaterials)

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20 pages, 4538 KiB

Open AccessEditor’s ChoiceArticle

Rheological Behavior of a New Mucoadhesive Oral Formulation Based on Sodium Chondroitin Sulfate, Xyloglucan and Glycerol

by Tiziana Maria Grazia Pecora, Barbara Ragazzo, Walter Bertin, Alessia Ragonese, Marco Mascagni, Paola Maffei and Rosario Pignatello

J. Funct. Biomater. 2021, 12(2), 28; https://doi.org/10.3390/jfb12020028 - 28 Apr 2021

Cited by 9 | Viewed by 3234

Abstract

Background: The study aimed at assessing the mucoadhesive properties and the barrier effect of a formulation, labelled as AL2106, containing sodium chondroitin sulfate (ChS), xyloglucan from tamarind seed extract, and glycerol, by evaluating the capacity to adhere to a layer of mucin, [...] Read more.

Background: The study aimed at assessing the mucoadhesive properties and the barrier effect of a formulation, labelled as AL2106, containing sodium chondroitin sulfate (ChS), xyloglucan from tamarind seed extract, and glycerol, by evaluating the capacity to adhere to a layer of mucin, the rheological synergism and the barrier effect in comparison to the marketed Esoxx One medical device. AL2106 is a medical device distributed by Alfasigma SpA, Italy with REF FTP57 (Manufacturer: Labomar SpA); it is analogous to Esoxx One medical device: the two products are drinkable solutions that, after swallowing, adhere to the esophageal mucosa, protecting it from the corrosive effect of the gastric acid reflux. AL2106 has been conceived to be better performing in terms of duration of the barrier effect compared to Esoxx One. Methods: The mucoadhesive properties, rheological behavior, buffering capacity against acidity, and film-forming ability with the resultant protecting effect on esophagus mucosa (caffeine permeation test) was compared between the two products. Results: The mucoadhesivity of the formulations was shown in vitro: both remained adherent to a mucin layer, also when the support was rotated by 90°, and when the film layer was washed with water, intended to simulate the washout due to swallowing. AL2106 showed a good buffering efficacy, being able to absorb at least 50% of its weight of 0.03 M HCl while maintaining the pH above 4. The film-forming effect and barrier properties of AL2106 and Esoxx One were confirmed by an in vitro study on reconstructed human esophageal epithelium. A greater film-forming efficacy of AL2106, lasting for at least 5 h, than Esoxx One was observed. Noteworthy, the barrier function of esophageal tissues was shown to be preserved after the application of both formulations. Conclusions: The combination of ChS with the mucoadhesive glycerol−xyloglucan complex and other excipients, which contribute to the barrier effect and to mucoadhesion, contained in AL2106, allowed a longer-lasting protective effect than Esoxx One, proving its effectivity and safety for oral use. Full article

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32 pages, 6894 KiB

Open AccessEditor’s ChoiceReview

Advances in Fabricating the Electrospun Biopolymer-Based Biomaterials

by Sebastian Wilk and Aleksandra Benko

J. Funct. Biomater. 2021, 12(2), 26; https://doi.org/10.3390/jfb12020026 - 16 Apr 2021

Cited by 34 | Viewed by 5001

Abstract

Biopolymers formed into a fibrous morphology through electrospinning are of increasing interest in the field of biomedicine due to their intrinsic biocompatibility and biodegradability and their ability to be biomimetic to various fibrous structures present in animal tissues. However, their mechanical properties are [...] Read more.

Biopolymers formed into a fibrous morphology through electrospinning are of increasing interest in the field of biomedicine due to their intrinsic biocompatibility and biodegradability and their ability to be biomimetic to various fibrous structures present in animal tissues. However, their mechanical properties are often unsatisfactory and their processing may be troublesome. Thus, extensive research interest is focused on improving these qualities. This review article presents the selection of the recent advances in techniques aimed to improve the electrospinnability of various biopolymers (polysaccharides, polynucleotides, peptides, and phospholipids). The electrospinning of single materials, and the variety of co-polymers, with and without additives, is covered. Additionally, various crosslinking strategies are presented. Examples of cytocompatibility, biocompatibility, and antimicrobial properties are analyzed. Special attention is given to whey protein isolate as an example of a novel, promising, green material with good potential in the field of biomedicine. This review ends with a brief summary and outlook for the biomedical applicability of electrospinnable biopolymers. Full article

(This article belongs to the Special Issue Bioinspired Materials for Medical and Biotechnological Applications)

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28 pages, 4822 KiB

Open AccessEditor’s ChoiceArticle

Human Adipose Stem Cells (hASCs) Grown on Biodegradable Microcarriers in Serum- and Xeno-Free Medium Preserve Their Undifferentiated Status

by Francesco Muoio, Stefano Panella, Valentin Jossen, Matias Lindner, Yves Harder, Michele Müller, Regine Eibl and Tiziano Tallone

J. Funct. Biomater. 2021, 12(2), 25; https://doi.org/10.3390/jfb12020025 - 16 Apr 2021

Cited by 8 | Viewed by 4300

Abstract

Human adipose stem cells (hASCs) are promising candidates for cell-based therapies, but they need to be efficiently expanded in vitro as they cannot be harvested in sufficient quantities. Recently, dynamic bioreactor systems operated with microcarriers achieved considerable high cell densities. Thus, they are [...] Read more.

Human adipose stem cells (hASCs) are promising candidates for cell-based therapies, but they need to be efficiently expanded in vitro as they cannot be harvested in sufficient quantities. Recently, dynamic bioreactor systems operated with microcarriers achieved considerable high cell densities. Thus, they are a viable alternative to static planar cultivation systems to obtain high numbers of clinical-grade hASCs. Nevertheless, the production of considerable biomass in a short time must not be achieved to the detriment of the cells’ quality. To facilitate the scalable expansion of hASC, we have developed a new serum- and xeno-free medium (UrSuppe) and a biodegradable microcarrier (BR44). In this study, we investigated whether the culture of hASCs in defined serum-free conditions on microcarriers (3D) or on planar (2D) cell culture vessels may influence the expression of some marker genes linked with the immature degree or the differentiated status of the cells. Furthermore, we investigated whether the biomaterials, which form our biodegradable MCs, may affect cell behavior and differentiation. The results confirmed that the quality and the undifferentiated status of the hASCs are very well preserved when they grow on BR44 MCs in defined serum-free conditions. Indeed, the ASCs showed a gene expression profile more compatible with an undifferentiated status than the same cells grown under standard planar conditions. Full article

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24 pages, 2613 KiB

Open AccessEditor’s ChoiceReview

Osteogenic Peptides and Attachment Methods Determine Tissue Regeneration in Modified Bone Graft Substitutes

by George Bullock, Joss Atkinson, Piergiorgio Gentile, Paul Hatton and Cheryl Miller

J. Funct. Biomater. 2021, 12(2), 22; https://doi.org/10.3390/jfb12020022 - 31 Mar 2021

Cited by 15 | Viewed by 3998

Abstract

The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides [...] Read more.

The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field. Full article

(This article belongs to the Special Issue Innovative Biomaterials for Tissue Engineering: Regeneration of Soft and Hard Tissues)

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16 pages, 5409 KiB

Open AccessEditor’s ChoiceArticle

Synthesis and Characterization of Polymer-Based Coatings Modified with Bioactive Ceramic and Bovine Serum Albumin

by Wioletta Florkiewicz, Dagmara Słota, Angelika Placek, Klaudia Pluta, Bożena Tyliszczak, Timothy E. L. Douglas and Agnieszka Sobczak-Kupiec

J. Funct. Biomater. 2021, 12(2), 21; https://doi.org/10.3390/jfb12020021 - 30 Mar 2021

Cited by 15 | Viewed by 3543

Abstract

This study involves the synthesis of hydroxyapatite and describes the preparation and characterization of polymer coatings based on poly(ethylene glycol) diacrylate and poly(ethylene glycol) and modified with bovine serum albumin and hydroxyapatite. Hydroxyapatite was obtained by wet chemical synthesis and characterized by X-ray [...] Read more.

This study involves the synthesis of hydroxyapatite and describes the preparation and characterization of polymer coatings based on poly(ethylene glycol) diacrylate and poly(ethylene glycol) and modified with bovine serum albumin and hydroxyapatite. Hydroxyapatite was obtained by wet chemical synthesis and characterized by X-ray diffraction and FTIR spectroscopy, and its Ca/P molar ratio was determined (1.69 ± 0.08). The ceramic and bovine serum albumin were used in the preparation of composite materials with the polymeric matrix. The chemical composition of coatings was characterized with FTIR spectroscopy, and their morphology was recorded with SEM imaging. Moreover, the measurements of surface roughness parameters and stereometric research were performed. The prepared coatings were subjected to in vitro studies in simulated body fluid and artificial saliva. Changes in chemical composition and morphology after immersion were examined with FTIR spectroscopy and SEM imaging. Based on the conducted research, it can be stated that applied modifiers promote the biomineralization process. The roughness analysis confirmed prepared materials were characterized by the micrometer-scale topography. The materials morphology and roughness, and the morphology of the newly formed apatite deposit, were dependent on the type of the used modifier, and the artificial fluid used in in vitro studies. Full article

(This article belongs to the Special Issue Bioinspired Materials for Medical and Biotechnological Applications)

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23 pages, 4134 KiB

Open AccessEditor’s ChoiceArticle

Mechanical and Degradation Properties of Hybrid Scaffolds for Tissue Engineered Heart Valve (TEHV)

by Rabia Nazir, Arne Bruyneel, Carolyn Carr and Jan Czernuszka

J. Funct. Biomater. 2021, 12(1), 20; https://doi.org/10.3390/jfb12010020 - 9 Mar 2021

Cited by 17 | Viewed by 3933

Abstract

In addition to biocompatibility, an ideal scaffold for the regeneration of valvular tissue should also replicate the natural heart valve extracellular matrix (ECM) in terms of biomechanical properties and structural stability. In our previous paper, we demonstrated the development of collagen type I [...] Read more.

In addition to biocompatibility, an ideal scaffold for the regeneration of valvular tissue should also replicate the natural heart valve extracellular matrix (ECM) in terms of biomechanical properties and structural stability. In our previous paper, we demonstrated the development of collagen type I and hyaluronic acid (HA)-based scaffolds with interlaced microstructure. Such hybrid scaffolds were found to be compatible with cardiosphere-derived cells (CDCs) to potentially regenerate the diseased aortic heart valve. This paper focused on the quantification of the effect of crosslinking density on the mechanical properties under dry and wet conditions as well as degradation resistance. Elastic moduli increased with increasing crosslinking densities, in the dry and wet state, for parent networks, whereas those of interlaced scaffolds were higher than either network alone. Compressive and storage moduli ranged from 35 ± 5 to 95 ± 5 kPa and 16 ± 2 kPa to 113 ± 6 kPa, respectively, in the dry state. Storage moduli, in the dry state, matched and exceeded those of human aortic valve leaflets (HAVL). Similarly, degradation resistance increased with increasing the crosslinking densities for collagen-only and HA-only scaffolds. Interlaced scaffolds showed partial degradation in the presence of either collagenase or hyaluronidase as compared to when exposed to both enzymes together. These results agree with our previous findings that interlaced scaffolds were composed of independent collagen and HA networks without crosslinking between them. Thus, collagen/HA interlaced scaffolds have the potential to fill in the niche for designing an ideal tissue engineered heart valve (TEHV). Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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17 pages, 775 KiB

Open AccessEditor’s ChoiceReview

Challenges and Innovations in Osteochondral Regeneration: Insights from Biology and Inputs from Bioengineering toward the Optimization of Tissue Engineering Strategies

by Pedro Morouço, Cristiana Fernandes and Wanda Lattanzi

J. Funct. Biomater. 2021, 12(1), 17; https://doi.org/10.3390/jfb12010017 - 27 Feb 2021

Cited by 19 | Viewed by 5333

Abstract

Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone [...] Read more.

Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone (corresponding to a IV grade according to the conventional radiographic classification by Berndt and Harty). Therefore, strategies for functional tissue regeneration should also aim at healing the subchondral bone and joint interface, besides hyaline cartilage. With the ambition of contributing to solving this problem, several research groups have been working intensively on the development of tailored implants that could promote that complex osteochondral regeneration. These implants may be manufactured through a wide variety of processes and use a wide variety of (bio)materials. This review aimed to examine the state of the art regarding the challenges, advantages, and drawbacks of the current strategies for osteochondral regeneration. One of the most promising approaches relies on the principles of additive manufacturing, where technologies are used that allow for the production of complex 3D structures with a high level of control, intended and predefined geometry, size, and interconnected pores, in a reproducible way. However, not all materials are suitable for these processes, and their features should be examined, targeting a successful regeneration. Full article

(This article belongs to the Special Issue Innovative Biomaterials for Tissue Engineering: Regeneration of Soft and Hard Tissues)

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17 pages, 6931 KiB

Open AccessEditor’s ChoiceArticle

Effects of Process Parameters on Structure and Properties of Melt-Blown Poly(Lactic Acid) Nonwovens for Skin Regeneration

by Ewa Dzierzkowska, Anna Scisłowska-Czarnecka, Marcin Kudzin, Maciej Boguń, Piotr Szatkowski, Marcin Gajek, Kamil Kornaus, Magdalena Chadzinska and Ewa Stodolak-Zych

J. Funct. Biomater. 2021, 12(1), 16; https://doi.org/10.3390/jfb12010016 - 26 Feb 2021

Cited by 24 | Viewed by 4077

Abstract

Skin regeneration requires a three-dimensional (3D) scaffold for cell adhesion, growth and proliferation. A type of the scaffold offering a 3D structure is a nonwoven material produced via a melt-blown technique. Process parameters of this technique can be adapted to improve the cellular [...] Read more.

Skin regeneration requires a three-dimensional (3D) scaffold for cell adhesion, growth and proliferation. A type of the scaffold offering a 3D structure is a nonwoven material produced via a melt-blown technique. Process parameters of this technique can be adapted to improve the cellular response. Polylactic acid (PLA) was used to produce a nonwoven scaffold by a melt-blown technique. The key process parameters, i.e., the head and air temperature, were changed in the range from 180–270 °C to obtain eight different materials (MB1–MB8). The relationships between the process parameters, morphology, porosity, thermal properties and the cellular response were explored in this study. The mean fiber diameters ranged from 3 to 120 µm. The average material roughness values were between 47 and 160 µm, whereas the pore diameters ranged from 5 to 400 µm. The calorimetry thermograms revealed a correlation between the temperature parameters and crystallization. The response of keratinocytes and macrophages exhibited a higher cell viability on thicker fibers. The cell-scaffold interaction was observed via SEM after 7 days. This result proved that the features of melt-blown nonwoven scaffolds depended on the processing parameters, such as head temperature and air temperature. Thanks to examinations, the most suitable scaffolds for skin tissue regeneration were selected. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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13 pages, 1613 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Dental Pulp Stem Cell Responses to Functional Biomaterials Including Mineralized Trioxide Aggregates

by Sejin Bae, Bueonguk Kang, Hyungbin Lee, Harrison Luu, Eric Mullins and Karl Kingsley

J. Funct. Biomater. 2021, 12(1), 15; https://doi.org/10.3390/jfb12010015 - 24 Feb 2021

Cited by 4 | Viewed by 2747

Abstract

Introduction: Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or [...] Read more.

Introduction: Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or in vivo growth, viability, and proliferation, as well as differentiation of DPSC—although much remains to be discovered. Based upon this information, the primary objective of this study was to understand the functional biomaterials needed to more effectively direct DPSC viability, growth, and proliferation. Methods: Using an approved protocol, previously collected and isolated samples of DPSC from an existing repository were used. Previously established stem cell biomarkers (Sox-2, Oct-4, NANOG) from each isolate were correlated with their proliferation rates or doubling times to categorize them into rapid, intermediate, or slow-dividing multipotent DPSC. Growth factors and other functional dental biomaterials were subsequently tested to evaluate DPSC responses in proliferation, viability, and morphology. Results: Differential responses were observed among DPSC isolates to growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic protein (BMP-2), and functional biomaterials such as mineralized trioxide aggregates (MTA). The responsiveness of DPSC isolates did not correlate with any single factor but rather with a combination of proliferation rate and biomarker expression. Conclusions: These data strongly suggest that some, but not all, DPSC isolates are capable of a robust and significant in vitro response to differentiation stimuli, although this response is not universal. Although some biomarkers and phenotypes that distinguish and characterize these DPSC isolates may facilitate the ability to predict growth, viability, and differentiation potential, more research is needed to determine the other intrinsic and extrinsic factors that may contribute to and modulate these DPSC responses to these functional biomaterials for biotechnology and bioengineering applications. Full article

(This article belongs to the Special Issue Recent Advances in Dental Implants and Biomaterials)

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15 pages, 5005 KiB

Open AccessEditor’s ChoiceArticle

Preliminary Studies on Graphene-Reinforced 3D Products Obtained by the One-Stage Sacrificial Template Method for Bone Reconstruction Applications

by Aura-Cătălina Mocanu, Florin Miculescu, George E. Stan, Robert-Cătălin Ciocoiu, Mihai Cosmin Corobea, Marian Miculescu and Lucian Toma Ciocan

J. Funct. Biomater. 2021, 12(1), 13; https://doi.org/10.3390/jfb12010013 - 12 Feb 2021

Cited by 6 | Viewed by 3437

Abstract

The bone remodeling field has shifted focus towards the delineation of products with two main critical attributes: internal architectures capable to promote fast cell colonization and good mechanical performance. In this paper, Luffa-fibers and graphene nanoplatelets were proposed as porogen template and [...] Read more.

The bone remodeling field has shifted focus towards the delineation of products with two main critical attributes: internal architectures capable to promote fast cell colonization and good mechanical performance. In this paper, Luffa-fibers and graphene nanoplatelets were proposed as porogen template and mechanical reinforcing agent, respectively, in view of framing 3D products by a one-stage polymer-free process. The ceramic matrix was prepared through a reproducible technology, developed for the conversion of marble resources into calcium phosphates (CaP) powders. After the graphene incorporation (by mechanical and ultrasonication mixing) into the CaP matrix, and Luffa-fibers addition, the samples were evaluated in both as-admixed and thermally-treated form (compact/porous products) by complementary structural, morphological, and compositional techniques. The results confirmed the benefits of the two agents’ addition upon the compact products’ micro-porosity and the global mechanical features, inferred by compressive strength and elastic modulus determinations. For the porous products, overall optimal results were obtained at a graphene amount of <1 wt.%. Further, no influence of graphene on fibers’ ability to generate at high temperatures internal interconnected-channels-arrays was depicted. Moreover, its incorporation led to a general preservation of structural composition and stability for both the as-admixed and thermally-treated products. The developed CaP-reinforced structures sustain the premises for prospective non- and load-bearing biomedical applications. Full article

(This article belongs to the Special Issue Bioceramics and Bioactive Glass-Based Materials)

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16 pages, 6683 KiB

Open AccessEditor’s ChoiceArticle

Long-Term Assessment of the In Vitro Corrosion Resistance of Biomimetic ACP Coatings Electrodeposited from an Acetate Bath

by Patrycja Osak, Joanna Maszybrocka, Julian Kubisztal, Patryk Ratajczak and Bożena Łosiewicz

J. Funct. Biomater. 2021, 12(1), 12; https://doi.org/10.3390/jfb12010012 - 7 Feb 2021

Cited by 15 | Viewed by 2674

Abstract

Calcium phosphate coatings are able to improve the osseointegration process due to their chemical composition, which is similar to that of bone tissues. In this work, to increase the long-term corrosion resistance and to improve the osseointegration process of commercially pure titanium Grade [...] Read more.

Calcium phosphate coatings are able to improve the osseointegration process due to their chemical composition, which is similar to that of bone tissues. In this work, to increase the long-term corrosion resistance and to improve the osseointegration process of commercially pure titanium Grade 4 (CpTi G4), biomimetic amorphous calcium phosphate (ACP) coatings were electrodeposited for the first time from an acetate bath with a pH level of 7.0 and a Ca:P ratio of 1.67. ACP coatings were obtained on CpTi G4 substrate subjected to sandblasting and autoclaving using electrochemically assisted deposition at a potential of −3 V relative to the open circuit potential for 30 min at room temperature. SEM, EDS, 2D roughness profiles, amplitude-sensitive eddy current method, and Kelvin scanning probe were used for the surface characterization of the biomaterial under study. In vitro corrosion resistance tests were conducted for 21 days in artificial saliva using open circuit potential, polarization curves, and electrochemical impedance spectroscopy measurements. The passive-transpassive behavior was revealed for the obtained ACP coatings. The long-term corrosion resistance test showed a deterioration of the protective properties for CpTi G4 uncoated and coated with ACP with immersion time. The mechanism and kinetics of the pitting corrosion on the CpTi G4|TiO₂|ACP coating system are discussed in detail. Full article

(This article belongs to the Special Issue Bioinspired Materials for Medical and Biotechnological Applications)

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16 pages, 3010 KiB

Open AccessEditor’s ChoiceArticle

Poly(methyl methacrylate) Bone Cement Composite Can Be Refilled with Antibiotics after Implantation in Femur or Soft Tissue

by Erika L. Cyphert, Ningjing Zhang, Dylan W. Marques, Greg D. Learn, Fang Zhang and Horst A. von Recum

J. Funct. Biomater. 2021, 12(1), 8; https://doi.org/10.3390/jfb12010008 - 26 Jan 2021

Cited by 6 | Viewed by 3139

Abstract

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for [...] Read more.

While periprosthetic joint infections (PJIs) result in a small percentage of patients following arthroplasties, they are challenging to treat if they spread into bone and soft tissue. Treatment involves delivering antibiotics using poly(methyl methacrylate) (PMMA) bone cement. However, antibiotic release is insufficient for prolonged infections. Previous work demonstrated efficacy of incorporating insoluble cyclodextrin (CD) microparticles into PMMA to improve antibiotic release and allow for post-implantation drug refilling to occur in a tissue-mimicking model. To simulate how antibiotic refilling may be possible in more physiologically relevant models, this work investigated development of bone and muscle refilling models. The bone refilling model involved embedding PMMA-CD into rabbit femur and administering antibiotic via intraosseous infusion. Muscle tissue refilling model involved implanting PMMA-CD beads in bovine muscle tissue and administering antibiotic via tissue injection. Duration of antimicrobial activity of refilled PMMA-CD was evaluated. PMMA-CD composite in bone and muscle tissue models was capable of being refilled with antibiotics and resulted in prolonged antimicrobial activity. PMMA-CD provided sustained and on-demand antimicrobial activity without removal of implant if infection develops. Intraosseous infusion appeared to be a viable technique to enable refilling of PMMA-CD after implantation in bone, reporting for the first time the ability to refill PMMA in bone. Full article

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10 pages, 7565 KiB

Open AccessEditor’s ChoiceArticle

Temporomandibular Joint Prostheses: Optimal Materials for the Optimal Stomatognathic System Performance—Preliminary Study

by Iwona Niedzielska, Michał Bąk, Damian Niedzielski, Hubert Okła, Jadwiga Gabor, Arkadiusz Stanula, Jarosław Paluch and Andrzej Szymon Swinarew

J. Funct. Biomater. 2021, 12(1), 7; https://doi.org/10.3390/jfb12010007 - 26 Jan 2021

Cited by 4 | Viewed by 3478

Abstract

The aim of this study was to quantitatively evaluate alloplastic Temporomandibular Joint (TMJ) Prostheses against other treatment modalities regarding the jaw kinematics. Six patients with Temporomandibular Joint Prostheses, four with mandibular ramus Patient-Specific Implant (PSI) with condylar head preservation, and four after mandibular [...] Read more.

The aim of this study was to quantitatively evaluate alloplastic Temporomandibular Joint (TMJ) Prostheses against other treatment modalities regarding the jaw kinematics. Six patients with Temporomandibular Joint Prostheses, four with mandibular ramus Patient-Specific Implant (PSI) with condylar head preservation, and four after mandibular condylectomy were evaluated by the means of axiography (Cadiax Compact 2), which is the noninvasive three-dimensional study of condylar movements. The patients were also evaluated clinically for the mandibular movements. The study revealed that the significant movement limitations occurred bilaterally in patients fitted with TMJ prosthesis. For the protrusion movement, the vector length of the movement (L) for the TMJ prosthesis was 0.31 vs. 3.01 mm for the PSI (Kruskal–Wallis chi-squared = 9.1667, df = 2, p-value = 0.01022, post hoc Dunn p-value = 0.015) and for the laterotrusion to the operated side, the length of the vector (L) was 0.66 vs. 3.35 mm, respectively. Statistically significant differences between groups were most frequent for the laterotrusion to the unoperated side. The study shows that a further development on TMJ Prostheses geometry and materials is needed. Full article

(This article belongs to the Special Issue Recent Advances in Dental Implants and Biomaterials)

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15 pages, 1784 KiB

Open AccessEditor’s ChoiceArticle

Functional Properties of Low-Modulus PMMA Bone Cements Containing Linoleic Acid

by Céline Robo, David Wenner, S. J. Kumari A. Ubhayasekera, Jöns Hilborn, Caroline Öhman-Mägi and Cecilia Persson

J. Funct. Biomater. 2021, 12(1), 5; https://doi.org/10.3390/jfb12010005 - 17 Jan 2021

Cited by 9 | Viewed by 3231

Abstract

Acrylic bone cements modified with linoleic acid are a promising low-modulus alternative to traditional high-modulus bone cements. However, several key properties remain unexplored, including the effect of autoclave sterilization and the potential use of low-modulus cements in other applications than vertebral augmentation. In [...] Read more.

Acrylic bone cements modified with linoleic acid are a promising low-modulus alternative to traditional high-modulus bone cements. However, several key properties remain unexplored, including the effect of autoclave sterilization and the potential use of low-modulus cements in other applications than vertebral augmentation. In this work, we evaluate the effect of sterilization on the structure and stability of linoleic acid, as well as in the handling properties, glass transition temperature, mechanical properties, and screw augmentation potential of low-modulus cement containing the fatty acid. Neither ¹H NMR nor SFC-MS/MS analysis showed any detectable differences in autoclaved linoleic acid compared to fresh one. The peak polymerization temperature of the low-modulus cement was much lower (28–30 °C) than that of the high-modulus cement (67 °C), whereas the setting time remained comparable (20–25 min). The T_g of the low-modulus cement was lower (75–78 °C) than that of the high-stiffness cement (103 °C). It was shown that sterilization of linoleic acid by autoclaving did not significantly affect the functional properties of low-modulus PMMA bone cement, making the component suitable for sterile production. Ultimately, the low-modulus cement exhibited handling and mechanical properties that more closely match those of osteoporotic vertebral bone with a screw holding capacity of under 2000 N, making it a promising alternative for use in combination with orthopedic hardware in applications where high-stiffness augmentation materials can result in undesired effects. Full article

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11 pages, 3417 KiB

Open AccessEditor’s ChoiceArticle

Mechanical Consequences of Dynamically Loaded NiTi Wires under Typical Actuator Conditions in Rehabilitation and Neuroscience

by Umut D. Çakmak, Zoltán Major and Michael Fischlschweiger

J. Funct. Biomater. 2021, 12(1), 4; https://doi.org/10.3390/jfb12010004 - 8 Jan 2021

Cited by 3 | Viewed by 2346

Abstract

In the field of rehabilitation and neuroscience, shape memory alloys play a crucial role as lightweight actuators. Devices are exploiting the shape memory effect by transforming heat into mechanical work. In rehabilitation applications, dynamic loading of the respective device occurs, which in turn [...] Read more.

In the field of rehabilitation and neuroscience, shape memory alloys play a crucial role as lightweight actuators. Devices are exploiting the shape memory effect by transforming heat into mechanical work. In rehabilitation applications, dynamic loading of the respective device occurs, which in turn influences the mechanical consequences of the phase transforming alloy. Hence in this work, dynamic thermomechanical material behavior of temperature-triggered phase transforming NiTi shape memory alloy (SMA) wires with different chemical compositions and geometries was experimentally investigated. Storage modulus and mechanical loss factor of NiTi alloys at different temperatures and loading frequencies were analyzed under force-controlled conditions. Counterintuitive storage modulus- and loss factor-dependent trends regarding the loading frequency dependency of the mechanical properties on the materials’ composition and geometry were, hence, obtained. It was revealed that loss factors showed a pronounced loading frequency dependency, whereas the storage modulus was not affected. It was shown that force-controlled conditions led to a lower storage modulus than expected. Furthermore, it turned out that a simple empirical relation could capture the characteristic temperature dependency of the storage modulus, which is an important input relation for modeling the rehabilitation device behavior under different dynamic and temperature loading conditions, taking directly into account the material behavior of the shape memory alloy. Full article

(This article belongs to the Special Issue Experimentation, Numerical and Analytical Methods in Functional Biomaterials)

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26 pages, 1069 KiB

Open AccessEditor’s ChoiceReview

Silver Nanoparticles: Mechanism of Action and Probable Bio-Application

by Ekaterina O. Mikhailova

J. Funct. Biomater. 2020, 11(4), 84; https://doi.org/10.3390/jfb11040084 - 26 Nov 2020

Cited by 273 | Viewed by 13883

Abstract

This review is devoted to the medical application of silver nanoparticles produced as a result of “green” synthesis using various living organisms (bacteria, fungi, plants). The proposed mechanisms of AgNPs synthesis and the action mechanisms on target cells are highlighted. Full article

(This article belongs to the Special Issue Bioactive Properties of Advanced Nanomaterials)

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11 pages, 1233 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Role of Scaffolds in Tendon Tissue Engineering

by Angelo V. Vasiliadis and Konstantinos Katakalos

J. Funct. Biomater. 2020, 11(4), 78; https://doi.org/10.3390/jfb11040078 - 1 Nov 2020

Cited by 39 | Viewed by 5786

Abstract

Tendons are unique forms of connective tissue aiming to transmit the mechanical force of muscle contraction to the bones. Tendon injury may be due to direct trauma or might be secondary to overuse injury and age-related degeneration, leading to inflammation, weakening and subsequent [...] Read more.

Tendons are unique forms of connective tissue aiming to transmit the mechanical force of muscle contraction to the bones. Tendon injury may be due to direct trauma or might be secondary to overuse injury and age-related degeneration, leading to inflammation, weakening and subsequent rupture. Current traditional treatment strategies focus on pain relief, reduction of the inflammation and functional restoration. Tendon repair surgery can be performed in people with tendon injuries to restore the tendon’s function, with re-rupture being the main potential complication. Novel therapeutic approaches that address the underlying pathology of the disease is warranted. Scaffolds represent a promising solution to the challenges associated with tendon tissue engineering. The ideal scaffold for tendon tissue engineering needs to exhibit physiologically relevant mechanical properties and to facilitate functional graft integration by promoting the regeneration of the native tissue. Full article

(This article belongs to the Special Issue Experimentation, Numerical and Analytical Methods in Functional Biomaterials)

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29 pages, 1146 KiB

Open AccessEditor’s ChoiceReview

Recent Advances of Conducting Polymers and Their Composites for Electrochemical Biosensing Applications

by John H. T. Luong, Tarun Narayan, Shipra Solanki and Bansi D. Malhotra

J. Funct. Biomater. 2020, 11(4), 71; https://doi.org/10.3390/jfb11040071 - 25 Sep 2020

Cited by 34 | Viewed by 5492

Abstract

Conducting polymers (CPs) have been at the center of research owing to their metal-like electrochemical properties and polymer-like dispersion nature. CPs and their composites serve as ideal functional materials for diversified biomedical applications like drug delivery, tissue engineering, and diagnostics. There have also [...] Read more.

Conducting polymers (CPs) have been at the center of research owing to their metal-like electrochemical properties and polymer-like dispersion nature. CPs and their composites serve as ideal functional materials for diversified biomedical applications like drug delivery, tissue engineering, and diagnostics. There have also been numerous biosensing platforms based on polyaniline (PANI), polypyrrole (PPY), polythiophene (PTP), and their composites. Based on their unique properties and extensive use in biosensing matrices, updated information on novel CPs and their role is appealing. This review focuses on the properties and performance of biosensing matrices based on CPs reported in the last three years. The salient features of CPs like PANI, PPY, PTP, and their composites with nanoparticles, carbon materials, etc. are outlined along with respective examples. A description of mediator conjugated biosensor designs and enzymeless CPs based glucose sensing has also been included. The future research trends with required improvements to improve the analytical performance of CP-biosensing devices have also been addressed. Full article

(This article belongs to the Special Issue Salient Features of Functional Polymers and Their Composites with Nanomaterials in Chemosensors and Biosensors)

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36 pages, 9300 KiB

Open AccessEditor’s ChoiceReview

Bio-Based Electrospun Fibers for Wound Healing

by Bahareh Azimi, Homa Maleki, Lorenzo Zavagna, Jose Gustavo De la Ossa, Stefano Linari, Andrea Lazzeri and Serena Danti

J. Funct. Biomater. 2020, 11(3), 67; https://doi.org/10.3390/jfb11030067 - 22 Sep 2020

Cited by 148 | Viewed by 11304

Abstract

Being designated to protect other tissues, skin is the first and largest human body organ to be injured and for this reason, it is accredited with a high capacity for self-repairing. However, in the case of profound lesions or large surface loss, the [...] Read more.

Being designated to protect other tissues, skin is the first and largest human body organ to be injured and for this reason, it is accredited with a high capacity for self-repairing. However, in the case of profound lesions or large surface loss, the natural wound healing process may be ineffective or insufficient, leading to detrimental and painful conditions that require repair adjuvants and tissue substitutes. In addition to the conventional wound care options, biodegradable polymers, both synthetic and biologic origin, are gaining increased importance for their high biocompatibility, biodegradation, and bioactive properties, such as antimicrobial, immunomodulatory, cell proliferative, and angiogenic. To create a microenvironment suitable for the healing process, a key property is the ability of a polymer to be spun into submicrometric fibers (e.g., via electrospinning), since they mimic the fibrous extracellular matrix and can support neo- tissue growth. A number of biodegradable polymers used in the biomedical sector comply with the definition of bio-based polymers (known also as biopolymers), which are recently being used in other industrial sectors for reducing the material and energy impact on the environment, as they are derived from renewable biological resources. In this review, after a description of the fundamental concepts of wound healing, with emphasis on advanced wound dressings, the recent developments of bio-based natural and synthetic electrospun structures for efficient wound healing applications are highlighted and discussed. This review aims to improve awareness on the use of bio-based polymers in medical devices. Full article

(This article belongs to the Special Issue High Performance Functional Bio-based Polymers for Skin-contact Products)

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17 pages, 11862 KiB

Open AccessEditor’s ChoiceArticle

Electrosprayed Chitin Nanofibril/Electrospun Polyhydroxyalkanoate Fiber Mesh as Functional Nonwoven for Skin Application

by Bahareh Azimi, Lily Thomas, Alessandra Fusco, Ozlem Ipek Kalaoglu-Altan, Pooja Basnett, Patrizia Cinelli, Karen De Clerck, Ipsita Roy, Giovanna Donnarumma, Maria-Beatrice Coltelli, Serena Danti and Andrea Lazzeri

J. Funct. Biomater. 2020, 11(3), 62; https://doi.org/10.3390/jfb11030062 - 3 Sep 2020

Cited by 49 | Viewed by 5760

Abstract

Polyhydroxyalkanoates (PHAs) are a family of bio-based polyesters that have found different biomedical applications. Chitin and lignin, byproducts of fishery and plant biomass, show antimicrobial and anti-inflammatory activity on the nanoscale. Due to their polarities, chitin nanofibril (CN) and nanolignin (NL) can be [...] Read more.

Polyhydroxyalkanoates (PHAs) are a family of bio-based polyesters that have found different biomedical applications. Chitin and lignin, byproducts of fishery and plant biomass, show antimicrobial and anti-inflammatory activity on the nanoscale. Due to their polarities, chitin nanofibril (CN) and nanolignin (NL) can be assembled into micro-complexes, which can be loaded with bioactive factors, such as the glycyrrhetinic acid (GA) and CN-NL/GA (CLA) complexes, and can be used to decorate polymer surfaces. This study aims to develop completely bio-based and bioactive meshes intended for wound healing. Poly(3-hydroxybutyrate)/Poly(3-hydroxyoctanoate-co-3-hydroxydecanoate), P(3HB)/P(3HO-co-3HD) was used to produce films and fiber meshes, to be surface-modified via electrospraying of CN or CLA to reach a uniform distribution. P(3HB)/P(3HO-co-3HD) fibers with desirable size and morphology were successfully prepared and functionalized with CN and CLA using electrospinning and tested in vitro with human keratinocytes. The presence of CN and CLA improved the indirect antimicrobial and anti-inflammatory activity of the electrospun fiber meshes by downregulating the expression of the most important pro-inflammatory cytokines and upregulating human defensin 2 expression. This natural and eco-sustainable mesh is promising in wound healing applications. Full article

(This article belongs to the Special Issue High Performance Functional Bio-based Polymers for Skin-contact Products)

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20 pages, 3361 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Biodegradable Polymeric Micro/Nano-Structures with Intrinsic Antifouling/Antimicrobial Properties: Relevance in Damaged Skin and Other Biomedical Applications

by Mario Milazzo, Giuseppe Gallone, Elena Marcello, Maria Donatella Mariniello, Luca Bruschini, Ipsita Roy and Serena Danti

J. Funct. Biomater. 2020, 11(3), 60; https://doi.org/10.3390/jfb11030060 - 19 Aug 2020

Cited by 31 | Viewed by 6622

Abstract

Bacterial colonization of implanted biomedical devices is the main cause of healthcare-associated infections, estimated to be 8.8 million per year in Europe. Many infections originate from damaged skin, which lets microorganisms exploit injuries and surgical accesses as passageways to reach the implant site [...] Read more.

Bacterial colonization of implanted biomedical devices is the main cause of healthcare-associated infections, estimated to be 8.8 million per year in Europe. Many infections originate from damaged skin, which lets microorganisms exploit injuries and surgical accesses as passageways to reach the implant site and inner organs. Therefore, an effective treatment of skin damage is highly desirable for the success of many biomaterial-related surgical procedures. Due to gained resistance to antibiotics, new antibacterial treatments are becoming vital to control nosocomial infections arising as surgical and post-surgical complications. Surface coatings can avoid biofouling and bacterial colonization thanks to biomaterial inherent properties (e.g., super hydrophobicity), specifically without using drugs, which may cause bacterial resistance. The focus of this review is to highlight the emerging role of degradable polymeric micro- and nano-structures that show intrinsic antifouling and antimicrobial properties, with a special outlook towards biomedical applications dealing with skin and skin damage. The intrinsic properties owned by the biomaterials encompass three main categories: (1) physical–mechanical, (2) chemical, and (3) electrostatic. Clinical relevance in ear prostheses and breast implants is reported. Collecting and discussing the updated outcomes in this field would help the development of better performing biomaterial-based antimicrobial strategies, which are useful to prevent infections. Full article

(This article belongs to the Special Issue High Performance Functional Bio-based Polymers for Skin-contact Products)

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17 pages, 4203 KiB

Open AccessEditor’s ChoiceArticle

Electrospun Scaffolds Containing Silver-Doped Hydroxyapatite with Antimicrobial Properties for Applications in Orthopedic and Dental Bone Surgery

by Thomas E. Paterson, Rui Shi, Jingjing Tian, Caroline J. Harrison, Mailys De Sousa Mendes, Paul V. Hatton, Zhou Li and Ilida Ortega

J. Funct. Biomater. 2020, 11(3), 58; https://doi.org/10.3390/jfb11030058 - 14 Aug 2020

Cited by 27 | Viewed by 4371

Abstract

Preventing the development of osteomyelitis while enhancing bone regeneration is challenging, with relatively little progress to date in translating promising technologies to the clinic. Nanoscale hydroxyapatite (nHA) has been employed as a bone graft substitute, and recent work has shown that it may [...] Read more.

Preventing the development of osteomyelitis while enhancing bone regeneration is challenging, with relatively little progress to date in translating promising technologies to the clinic. Nanoscale hydroxyapatite (nHA) has been employed as a bone graft substitute, and recent work has shown that it may be modified with silver to introduce antimicrobial activity against known pathogens. The aim of this study was to incorporate silver-doped nHA into electrospun scaffolds for applications in bone repair. Silver-doped nHA was produced using a modified, rapid mixing, wet precipitation method at 2, 5, 10 mol.% silver. The silver-doped nHA was added at 20 wt.% to a polycaprolactone solution for electrospinning. Bacteria studies demonstrated reduced bacterial presence, with Escherichia coli and Staphylococcus aureus undetectable after 96 h of exposure. Mesenchymal stem cells (MSCs) were used to study both toxicity and osteogenicity of the scaffolds using PrestoBlue^® and alkaline phosphatase (ALP) assays. Innovative silver nHA scaffolds significantly reduced E. coli and S. aureus bacterial populations while maintaining cytocompatibility with mammalian cells and enhancing the differentiation of MSCs into osteoblasts. It was concluded that silver-doped nHA containing scaffolds have the potential to act as an antimicrobial device while supporting bone tissue healing for applications in orthopedic and dental bone surgery. Full article

(This article belongs to the Special Issue Bacterial Interactions with Dental and Medical Materials)

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24 pages, 8934 KiB

Open AccessEditor’s ChoiceReview

Natural Architectures for Tissue Engineering and Regenerative Medicine

by Floris Honig, Steven Vermeulen, Amir A. Zadpoor, Jan de Boer and Lidy E. Fratila-Apachitei

J. Funct. Biomater. 2020, 11(3), 47; https://doi.org/10.3390/jfb11030047 - 7 Jul 2020

Cited by 11 | Viewed by 5569

Abstract

The ability to control the interactions between functional biomaterials and biological systems is of great importance for tissue engineering and regenerative medicine. However, the underlying mechanisms defining the interplay between biomaterial properties and the human body are complex. Therefore, a key challenge is [...] Read more.

The ability to control the interactions between functional biomaterials and biological systems is of great importance for tissue engineering and regenerative medicine. However, the underlying mechanisms defining the interplay between biomaterial properties and the human body are complex. Therefore, a key challenge is to design biomaterials that mimic the in vivo microenvironment. Over millions of years, nature has produced a wide variety of biological materials optimised for distinct functions, ranging from the extracellular matrix (ECM) for structural and biochemical support of cells to the holy lotus with special wettability for self-cleaning effects. Many of these systems found in biology possess unique surface properties recognised to regulate cell behaviour. Integration of such natural surface properties in biomaterials can bring about novel cell responses in vitro and provide greater insights into the processes occurring at the cell-biomaterial interface. Using natural surfaces as templates for bioinspired design can stimulate progress in the field of regenerative medicine, tissue engineering and biomaterials science. This literature review aims to combine the state-of-the-art knowledge in natural and nature-inspired surfaces, with an emphasis on material properties known to affect cell behaviour. Full article

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11 pages, 3497 KiB

Open AccessEditor’s ChoiceArticle

Time-Transient Effects of Silver and Copper in the Porous Titanium Dioxide Layer on Antibacterial Properties

by Masaya Shimabukuro, Akari Hiji, Tomoyo Manaka, Kosuke Nozaki, Peng Chen, Maki Ashida, Yusuke Tsutsumi, Akiko Nagai and Takao Hanawa

J. Funct. Biomater. 2020, 11(2), 44; https://doi.org/10.3390/jfb11020044 - 22 Jun 2020

Cited by 20 | Viewed by 3982

Abstract

Recently, silver (Ag) and copper (Cu) have been incorporated into a titanium (Ti) surface to realize their antibacterial property. This study investigated both the durability of the antibacterial effect and the surface change of the Ag- and Cu-incorporated porous titanium dioxide (TiO₂ [...] Read more.

Recently, silver (Ag) and copper (Cu) have been incorporated into a titanium (Ti) surface to realize their antibacterial property. This study investigated both the durability of the antibacterial effect and the surface change of the Ag- and Cu-incorporated porous titanium dioxide (TiO₂) layer. Ag- and Cu-incorporated TiO₂ layers were formed by micro-arc oxidation (MAO) treatment using the electrolyte with Ag and Cu ions. Ag- and Cu-incorporated specimens were incubated in saline during a period of 0–28 days. The changes in both the concentrations and chemical states of the Ag and Cu were characterized using X-ray photoelectron spectroscopy (XPS). The durability of the antibacterial effects against Escherichia coli (E. coli) were evaluated by the international organization for standardization (ISO) method. As a result, the Ag- and Cu-incorporated porous TiO₂ layers were formed on a Ti surface by MAO. The chemical state of Ag changed from Ag₂O to metallic Ag, whilst that of Cu did not change by incubation in saline for up to 28 days. Cu existed as a stable Cu₂O compound in the TiO₂ layer during the 28 days of incubation in saline. The concentrations of Ag and Cu were dramatically decreased by incubation for up to 7 days, and remained a slight amount until 28 days. The antibacterial effect of Ag-incorporated specimens diminished, and that of Cu was maintained even after incubation in saline. Our study suggests the importance of the time-transient effects of Ag and Cu on develop their antibacterial effects. Full article

(This article belongs to the Special Issue Bacterial Interactions with Dental and Medical Materials)

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