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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological and Bio- Materials".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 38009

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Dr. Jayakumar Rajadas

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Guest Editor

Biomaterials and Advanced Drug Delivery Laboratory, Stanford University, Stanford, CA, USA
Interests: biomaterial; drug delivery; regeneration medicine; wound healing; neurodegenerative disorders
Special Issues, Collections and Topics in MDPI journals

Dr. Mustafeez Mujtaba Babar

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Co-Guest Editor

Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad, Pakistan
Interests: biomaterials; formulation engineering; biotechnology; virology; infectious diseases; clinical education
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Novel materials including nanoparticles play a significant role in drug delivery for the treatment of diseases, vaccine delivery and tissue regeneration. Specifically, smart biomaterials and nanoparticles are widely used for targeted delivery.

This Special Issue of Biomolecules will focus on the most recent advances including micro-/nanocarrier-based materials, the synthesis or conjugation of novel materials, and protein/peptide-based biomaterials for biomedical applications. Current advances in the development of these novel materials including multifunctional liposomes, microneedles, microdroplets, nanoparticles, and other micro-/nanocarriers for disease treatment and skin and vascular regeneration will be addressed. Discussion on designing novel micro-/nanocarriers, drug delivery, and the synthesis or conjugation of novel materials with currently available FDA-approved drugs in biomedical applications will also be encouraged in this context. Both research and review articles proposing novelties are welcome.

Prof. Dr. Jayakumar Rajadas
Dr. Mustafeez Mujtaba Babar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

micro-/nanocarriers
synthesis or conjugation of biomaterials
drug delivery
targeted therapy/immunotherapy for combinatorial treatment
regenerative medicine/tissue engineering

Related Special Issue

Novel Materials for Biomedical Applications II in Biomolecules (6 articles)

Published Papers (13 papers)

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Research

Jump to: Review

16 pages, 17112 KiB

Open AccessArticle

Bioactive PEEK: Surface Enrichment of Vitronectin-Derived Adhesive Peptides

by Leonardo Cassari, Annj Zamuner, Grazia M. L. Messina, Martina Marsotto, Hongyi Chen, Giovanni Gonnella, Trevor Coward, Chiara Battocchio, Jie Huang, Giovanna Iucci, Giovanni Marletta, Lucy Di Silvio and Monica Dettin

Biomolecules 2023, 13(2), 246; https://doi.org/10.3390/biom13020246 - 28 Jan 2023

Cited by 4 | Viewed by 1678

Abstract

Polyetheretherketone (PEEK) is a thermoplastic polymer that has been recently employed for bone tissue engineering as a result of its biocompatibility and mechanical properties being comparable to human bone. PEEK, however, is a bio-inert material and, when implanted, does not interact with the host tissues, resulting in poor integration. In this work, the surfaces of 3D-printed PEEK disks were functionalized with: (i) an adhesive peptide reproducing [351–359] h-Vitronectin sequence (HVP) and (ii) HVP retro-inverted dimer (D2HVP), that combines the bioactivity of the native sequence (HVP) with the stability toward proteolytic degradation. Both sequences were designed to be anchored to the polymer surface through specific covalent bonds via oxime chemistry. All functionalized PEEK samples were characterized by Water Contact Angle (WCA) measurements, Atomic Force Microscopy (AFM), and X-ray Photoelectron Spectroscopy (XPS) to confirm the peptide enrichment. The biological results showed that both peptides were able to increase cell proliferation at 3 and 21 days. D2HVP functionalized PEEK resulted in an enhanced proliferation across all time points investigated with higher calcium deposition and more elongated cell morphology. Full article

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

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13 pages, 7340 KiB

Open AccessArticle

Decellularized Matrix Induced Spontaneous Odontogenic and Osteogenic Differentiation in Periodontal Cells

by Alexey A. Ivanov, Tamara I. Danilova, Alla V. Kuznetsova, Olga P. Popova and Oleg O. Yanushevich

Biomolecules 2023, 13(1), 122; https://doi.org/10.3390/biom13010122 - 06 Jan 2023

Cited by 2 | Viewed by 1405

Abstract

The regeneration of periodontal tissues is a decisive factor in the treatment of periodontitis. Currently, to achieve complete periodontal regeneration, many studies have evaluated the effectiveness of decellularized tissue-engineered constructs on periodontal regeneration. We studied the possibilities of osteogenic and odontogenic differentiation of periodontal progenitor and stem cells (SCs) of the periosteum and periodontal ligament, in decellularized tooth matrix (dTM) and periodontal ligament (dPDL), in 2D and 3D culture. The cell culture of periodontal cells without decellularized matrices was used as control. On the 14th day of cultivation of PDLSCs, PSCs, and PDLSCs + PSCs on dTM and/or dPDL scaffolds in 2D conditions, in all scaffold variants, a dense monolayer of spindle-shaped cells was intensely stained for markers of osteogenic differentiation, such as osteopontin and osteocalcin. Periodontal cells in the collagen I hydrogel (3D-dimensional culture) were more diverse in shape and, in combination of dTM and dPDL, in addition to osteogenic expression, expressed dentin sialophosphoprotein, an odontogenic differentiation marker. Thus, collagen I hydrogel contributed to the formation of conditions similar to those in vivo, and the combination of dTM with dPDL apparently formed a microenvironment that promoted osteogenic and odontogenic differentiation of periodontal cells. Full article

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

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28 pages, 3390 KiB

Open AccessArticle

Optimization of an Injectable, Resorbable, Bioactive Cement Able to Release the Anti-Osteoclastogenic Biomolecule ICOS-Fc for the Treatment of Osteoporotic Vertebral Compression Fractures

by Federica Banche-Niclot, Ilaria Corvaglia, Caterina Cavalera, Elena Boggio, Casimiro Luca Gigliotti, Umberto Dianzani, Antzela Tzagiollari, Nicholas Dunne, Antonio Manca, Sonia Fiorilli and Chiara Vitale-Brovarone

Biomolecules 2023, 13(1), 94; https://doi.org/10.3390/biom13010094 - 02 Jan 2023

Cited by 7 | Viewed by 2417

Abstract

Vertebral compression fractures are typical of osteoporosis and their treatment can require the injection of a cement through a minimally invasive procedure to restore vertebral body height. This study reports the development of an injectable calcium sulphate-based composite cement able to stimulate bone regeneration while inhibiting osteoclast bone resorption. To this aim, different types of strontium-containing mesoporous glass particles (Sr-MBG) were added to calcium sulphate powder to impart a pro-osteogenic effect, and the influence of their size and textural features on the cement properties was investigated. Anti-osteoclastogenic properties were conferred by incorporating into poly(lactic-co-glycolic)acid (PLGA) nanoparticles, a recombinant protein able to inhibit osteoclast activity (i.e., ICOS-Fc). Radiopaque zirconia nanoparticles (ZrO₂) were also added to the formulation to visualize the cement injection under fluoroscopy. The measured cement setting times were suitable for the clinical practice, and static mechanical testing determined a compressive strength of ca. 8 MPa, comparable to that of human vertebral bodies. In vitro release experiments indicated a sustained release of ICOS-Fc and Sr²⁺ ions up to 28 days. Overall, the developed cement is promising for the treatment of vertebral compression fractures and has the potential to stimulate bone regeneration while releasing a biomolecule able to limit bone resorption. Full article

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

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12 pages, 1653 KiB

Open AccessArticle

Flow Simulation and Gradient Printing of Fluorapatite- and Cell-Loaded Recombinant Spider Silk Hydrogels

by Vanessa J. Neubauer, Florian Hüter, Johannes Wittmann, Vanessa T. Trossmann, Claudia Kleinschrodt, Bettina Alber-Laukant, Frank Rieg and Thomas Scheibel

Biomolecules 2022, 12(10), 1413; https://doi.org/10.3390/biom12101413 - 03 Oct 2022

Cited by 2 | Viewed by 1652

Abstract

Hierarchical structures are abundant in almost all tissues of the human body. Therefore, it is highly important for tissue engineering approaches to mimic such structures if a gain of function of the new tissue is intended. Here, the hierarchical structures of the so-called enthesis, a gradient tissue located between tendon and bone, were in focus. Bridging the mechanical properties from soft to hard secures a perfect force transmission from the muscle to the skeleton upon locomotion. This study aimed at a novel method of bioprinting to generate gradient biomaterial constructs with a focus on the evaluation of the gradient printing process. First, a numerical approach was used to simulate gradient formation by computational flow as a prerequisite for experimental bioprinting of gradients. Then, hydrogels were printed in a single cartridge printing set-up to transfer the findings to biomedically relevant materials. First, composites of recombinant spider silk hydrogels with fluorapatite rods were used to generate mineralized gradients. Then, fibroblasts were encapsulated in the recombinant spider silk-fluorapatite hydrogels and gradually printed using unloaded spider silk hydrogels as the second component. Thereby, adjustable gradient features were achieved, and multimaterial constructs were generated. The process is suitable for the generation of gradient materials, e.g., for tissue engineering applications such as at the tendon/bone interface. Full article

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

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10 pages, 777 KiB

Open AccessArticle

Validation of a Commercial Enzyme-Linked Immunosorbent Assay for Allopregnanolone in the Saliva of Healthy Pregnant Women

by Maria Katharina Grötsch, Denise Margret Wietor, Timm Hettich and Ulrike Ehlert

Biomolecules 2022, 12(10), 1381; https://doi.org/10.3390/biom12101381 - 27 Sep 2022

Cited by 2 | Viewed by 1599

Abstract

Enzyme-linked immunosorbent assays (ELISAs) for saliva are simple, non-invasive methods for hormone detection. Allopregnanolone (ALLO) is a neuroactive steroid hormone that plays a crucial role in the aetiology of reproductive mood disorders. To better understand the relationship between ALLO and mood, a validated method to measure peripheral hormone levels is required. Currently, there is no commercially available ELISA with which to measure ALLO in saliva. We validated two ELISAs, developed for use with blood, with the saliva samples of 25 pregnant women, examining the range and sensitivity, intra- and inter-assay precision, parallelism, linearity of dilution, and recovery. The samples were simultaneously analysed using the liquid-chromatography–mass-spectrometry (LC-MS) method. The kits differed in range (31.2–2000 pg/mL vs. 1.6–100 ng/mL) and sensitivity (<9.5 pg/mL vs. 0.9 ng/mL), with the latter showing significant matrix effects and the former fulfilling the acceptance criteria of all the parameters. The concentrations measured with LC–MS were below the lower limit of quantification (<1.0 ng/mL) and no signal was detected. One of the tested ELISAs is a valid method for detecting ALLO in the saliva of pregnant women. It has a suitable measurement range and higher sensitivity than the conventional LC–MS method. Full article

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

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20 pages, 7476 KiB

Open AccessEditor’s ChoiceArticle

Regenerative Potential of A Bovine ECM-Derived Hydrogel for Biomedical Applications

by Dalila Di Francesco, Fabio Bertani, Luca Fusaro, Nausicaa Clemente, Flavia Carton, Maria Talmon, Luigia Grazia Fresu and Francesca Boccafoschi

Biomolecules 2022, 12(9), 1222; https://doi.org/10.3390/biom12091222 - 02 Sep 2022

Cited by 9 | Viewed by 1952

Abstract

Recent advancements in regenerative medicine have enhanced the development of biomaterials as multi-functional dressings, capable of accelerating wound healing and addressing the challenge of chronic wounds. Hydrogels obtained from decellularized tissues have a complex composition, comparable to the native extracellular environment, showing highly interesting characteristics for wound healing applications. In this study, a bovine pericardium decellularized extracellular matrix (dECM) hydrogel was characterized in terms of macromolecules content, and its immunomodulatory, angiogenic and wound healing potential has been evaluated. The polarization profile of human monocytes-derived macrophages seeded on dECM hydrogel was assessed by RT-qPCR. Angiogenic markers expression has been evaluated by Western blot and antibody array on cell lysates derived from endothelial cells cultured on dECM hydrogel, and a murine in vivo model of hindlimb ischemia was used to evaluate the angiogenic potential. Fibroblast migration was assessed by a transwell migration assay, and an in vivo murine wound healing model treated with dECM hydrogels was also used. The results showed a complex composition, of which the major component is collagen type I. The dECM hydrogel is biocompatible, able to drive M2 phenotype polarization, stimulate the expression of angiogenic markers in vitro, and prevent loss of functionality in hindlimb ischemia model. Furthermore, it drives fibroblast migration and shows ability to facilitate wound closure in vivo, demonstrating its great potential for regenerative applications. Full article

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

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13 pages, 4288 KiB

Open AccessArticle

High-Throughput Proteomic Analysis of Human Dermal Fibroblast Response to Different Blood Derivatives: Autologous Topical Serum Derived from Plasma Rich in Growth Factors (PRGF) versus Leukocyte- and Platelet-Rich Plasma (L-PRP)

by Eduardo Anitua, Ander Pino, Mikel Azkargorta, Felix Elortza and Roberto Prado

Biomolecules 2022, 12(7), 1002; https://doi.org/10.3390/biom12071002 - 19 Jul 2022

Cited by 2 | Viewed by 2020

Abstract

Platelet-rich plasma (PRP) is nowadays used in the treatment of different types of cutaneous lesions. However, different compositions can influence clinical outcomes. Among them, the inclusion of leukocytes is controversial. High-throughput proteomics techniques were used to analyze the proteins that are differentially expressed in human dermal fibroblasts (HDFs) after treatment for 24 h with two PRP types, autologous topical serum (Endoret serum—ES) derived from plasma rich in growth factors (PRGF) and leukocyte- and platelet-rich plasma (L-PRP). The identified proteins were then classified by both Gene Ontology and Ingenuity Pathway Analysis. The obtained results show that the compositions of ES and L-PRP differ in such a way that they induce different responses in HDFs. ES-treated HDFs overexpress growth factor-related proteins, leading to protein synthesis, cell proliferation and migration. By contrast, L-PRP treatment induces a response similar to that caused by proinflammatory molecules. These data could explain the contradictory clinical results obtained for the different types of PRP, especially with respect to their leukocyte contents. Full article

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

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Review

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32 pages, 1452 KiB

Open AccessReview

The Impact of Flavonoid-Loaded Nanoparticles in the UV Protection and Safety Profile of Topical Sunscreens

by Magda Fonseca, Mubashar Rehman, Raquel Soares and Pedro Fonte

Biomolecules 2023, 13(3), 493; https://doi.org/10.3390/biom13030493 - 07 Mar 2023

Cited by 4 | Viewed by 3875

Abstract

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings. Full article

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

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19 pages, 1044 KiB

Open AccessEditor’s ChoiceReview

Surface Treatments of PEEK for Osseointegration to Bone

by Jay R. Dondani, Janaki Iyer and Simon D. Tran

Biomolecules 2023, 13(3), 464; https://doi.org/10.3390/biom13030464 - 02 Mar 2023

Cited by 17 | Viewed by 2734

Abstract

Polymers, in general, and Poly (Ether-Ether-Ketone) (PEEK) have emerged as potential alternatives to conventional osseous implant biomaterials. Due to its distinct advantages over metallic implants, PEEK has been gaining increasing attention as a prime candidate for orthopaedic and dental implants. However, PEEK has a highly hydrophobic and bioinert surface that attenuates the differentiation and proliferation of osteoblasts and leads to implant failure. Several improvements have been made to the osseointegration potential of PEEK, which can be classified into three main categories: (1) surface functionalization with bioactive agents by physical or chemical means; (2) incorporation of bioactive materials either as surface coatings or as composites; and (3) construction of three-dimensionally porous structures on its surfaces. The physical treatments, such as plasma treatments of various elements, accelerated neutron beams, or conventional techniques like sandblasting and laser or ultraviolet radiation, change the micro-geometry of the implant surface. The chemical treatments change the surface composition of PEEK and should be titrated at the time of exposure. The implant surface can be incorporated with a bioactive material that should be selected following the desired use, loading condition, and antimicrobial load around the implant. For optimal results, a combination of the methods above is utilized to compensate for the limitations of individual methods. This review summarizes these methods and their combinations for optimizing the surface of PEEK for utilization as an implanted biomaterial. Full article

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

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16 pages, 1862 KiB

Open AccessEditor’s ChoiceReview

Recent Developments in Biopolymer-Based Hydrogels for Tissue Engineering Applications

by Rikako Hama, Anudari Ulziibayar, James W. Reinhardt, Tatsuya Watanabe, John Kelly and Toshiharu Shinoka

Biomolecules 2023, 13(2), 280; https://doi.org/10.3390/biom13020280 - 02 Feb 2023

Cited by 31 | Viewed by 3299

Abstract

Hydrogels are being investigated for their application in inducing the regeneration of various tissues, and suitable conditions for each tissue are becoming more apparent. Conditions such as the mechanical properties, degradation period, degradation mechanism, and cell affinity can be tailored by changing the molecular structure, especially in the case of polymers. Furthermore, many high-functional hydrogels with drug delivery systems (DDSs), in which drugs or bioactive substances are contained in controlled hydrogels, have been reported. This review focuses on the molecular design and function of biopolymer-based hydrogels and introduces recent developments in functional hydrogels for clinical applications. Full article

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

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18 pages, 3299 KiB

Open AccessFeature PaperReview

Localized Perivascular Therapeutic Approaches to Inhibit Venous Neointimal Hyperplasia in Arteriovenous Fistula Access for Hemodialysis Use

by Allan John R. Barcena, Joy Vanessa D. Perez, Olivia Liu, Amy Mu, Francisco M. Heralde III, Steven Y. Huang and Marites P. Melancon

Biomolecules 2022, 12(10), 1367; https://doi.org/10.3390/biom12101367 - 24 Sep 2022

Cited by 9 | Viewed by 5308

Abstract

An arteriovenous fistula (AVF) is the preferred vascular access for chronic hemodialysis, but high failure rates restrict its use. Optimizing patients’ perioperative status and the surgical technique, among other methods for preventing primary AVF failure, continue to fall short in lowering failure rates in clinical practice. One of the predominant causes of AVF failure is neointimal hyperplasia (NIH), a process that results from the synergistic effects of inflammation, hypoxia, and hemodynamic shear stress on vascular tissue. Although several systemic therapies have aimed at suppressing NIH, none has shown a clear benefit towards this goal. Localized therapeutic approaches may improve rates of AVF maturation by providing direct structural and functional support to the maturating fistula, as well as by delivering higher doses of pharmacologic agents while avoiding the adverse effects associated with systemic administration of therapeutic agents. Novel materials—such as polymeric scaffolds and nanoparticles—have enabled the development of different perivascular therapies, such as supportive mechanical devices, targeted drug delivery, and cell-based therapeutics. In this review, we summarize various perivascular therapeutic approaches, available data on their effectiveness, and the outlook for localized therapies targeting NIH in the setting of AVF for hemodialysis use. Highlights: Most systemic therapies do not improve AVF patency outcomes; therefore, localized therapeutic approaches may be beneficial. Locally delivered drugs and medical devices may improve AVF patency outcomes by providing biological and mechanical support. Cell-based therapies have shown promise in suppressing NIH by delivering a more extensive array of bioactive substances in response to the biochemical changes in the AVF microenvironment. Full article

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

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30 pages, 5956 KiB

Open AccessReview

Application of Metal–Organic Framework in Diagnosis and Treatment of Diabetes

by Qian Gao, Que Bai, Caiyun Zheng, Na Sun, Jinxi Liu, Wenting Chen, Fangfang Hu and Tingli Lu

Biomolecules 2022, 12(9), 1240; https://doi.org/10.3390/biom12091240 - 05 Sep 2022

Cited by 9 | Viewed by 4215

Abstract

Diabetes-related chronic wounds are often accompanied by a poor wound-healing environment such as high glucose, recurrent infections, and inflammation, and standard wound treatments are fairly limited in their ability to heal these wounds. Metal–organic frameworks (MOFs) have been developed to improve therapeutic outcomes due to their ease of engineering, surface functionalization, and therapeutic properties. In this review, we summarize the different synthesis methods of MOFs and conduct a comprehensive review of the latest research progress of MOFs in the treatment of diabetes and its wounds. State-of-the-art in vivo oral hypoglycemic strategies and the in vitro diagnosis of diabetes are enumerated and different antimicrobial strategies (including physical contact, oxidative stress, photothermal, and related ions or ligands) and provascular strategies for the treatment of diabetic wounds are compared. It focuses on the connections and differences between different applications of MOFs as well as possible directions for improvement. Finally, the potential toxicity of MOFs is also an issue that we cannot ignore. Full article

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

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23 pages, 2859 KiB

Open AccessReview

Biosensor-Integrated Drug Delivery Systems as New Materials for Biomedical Applications

by Iwona Cicha, Ronny Priefer, Patrícia Severino, Eliana B. Souto and Sona Jain

Biomolecules 2022, 12(9), 1198; https://doi.org/10.3390/biom12091198 - 29 Aug 2022

Cited by 9 | Viewed by 4116

Abstract

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients’ quality of life with chronic diseases are discussed. Full article

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

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