J. Funct. Biomater., Volume 14, Issue 10 (October 2023) – 48 articles

Composite materials used in dental restorations are considered resistant, long-lasting and aesthetic. As the wear of restorations is an important element in long-term use, the aim of this study was to evaluate the surface condition of nanohybrid and microfilled composite resins, after being subjected to the erosive action of dental bleaching protocols. This paper reflects a comparative study between one nanofilled composite and three microfilled composites used in restorations. For each composite, three sets of samples (under the form of composite discs) were created: a control group, an “office bleach” group with discs bleached with 40% hydrogen peroxide gel, and a “home bleach” group with discs bleached with 16% carbamide peroxide gel. Wear was numerically determined as the trace and the coefficients of friction obtained using a tribometer, the ball-on-disk test method, and two balls: alumina and sapphire. For all composite groups, there were statistically significant differences between the wear corresponding to the control and bleaching groups, for both testing balls. Regarding the composite type, the largest traces were recorded for GC Gradia direct anterior, for all groups, using the alumina ball. In contrast, for the sapphire ball, 3M ESPE Filtek Z550 was characterized by the largest traces. With respect to the friction coefficients, the “office bleach” group recorded the largest values, no matter the composite or the ball type used. The 3M ESPE Valux Plus composite recorded the largest friction coefficients for the alumina ball, and 3M ESPE Filtek Z550 for the sapphire ball. Overall, the “office bleach” group was characterized by higher composite wear, compared to the “home bleach” protocol or control group. Nanofilled composite resins showed superior wear resistance to microfilled resins after undergoing a bleaching protocol. Full article

Biological tissues from various anatomical sources have been utilized for tissue transplantation and have developed into an important source of extracellular scaffolding material for regenerative medicine applications. Tissue scaffolds ideally integrate with host tissue and provide a homeostatic environment for cellular infiltration, growth, differentiation, and tissue resolution. The human amniotic membrane is considered an important source of scaffolding material due to its 3D structural architecture and function and as a source of growth factors and cytokines. This tissue source has been widely studied and used in various areas of tissue repair including intraoral reconstruction, corneal repair, tendon repair, microvascular reconstruction, nerve procedures, burns, and chronic wound treatment. The production of amniotic membrane allografts has not been standardized, resulting in a wide array of amniotic membrane products, including single, dual, and tri-layered products, such as amnion, chorion, amnion–chorion, amnion–amnion, and amnion–chorion–amnion allografts. Since these allografts are not processed using the same methods, they do not necessarily produce the same clinical responses. The aim of this review is to highlight the properties of different human allograft membranes, present the different processing and preservation methods, and discuss their use in tissue engineering and regenerative applications. Full article

Despite significant advancements in dental tissue restoration and the use of prostheses for addressing tooth loss, the prevailing clinical approaches remain somewhat inadequate for replicating native dental tissue characteristics. The emergence of three-dimensional (3D) bioprinting offers a promising innovation within the fields of regenerative medicine and tissue engineering. This technology offers notable precision and efficiency, thereby introducing a fresh avenue for tissue regeneration. Unlike the traditional framework encompassing scaffolds, cells, and signaling factors, 3D bioprinting constitutes a contemporary addition to the arsenal of tissue engineering tools. The ongoing shift from conventional dentistry to a more personalized paradigm, principally under the guidance of bioprinting, is poised to exert a significant influence in the foreseeable future. This systematic review undertakes the task of aggregating and analyzing insights related to the application of bioprinting in the context of regenerative dentistry. Adhering to PRISMA guidelines, an exhaustive literature survey spanning the years 2019 to 2023 was performed across prominent databases including PubMed, Scopus, Google Scholar, and ScienceDirect. The landscape of regenerative dentistry has ushered in novel prospects for dentoalveolar treatments and personalized interventions. This review expounds on contemporary accomplishments and avenues for the regeneration of pulp—dentin, bone, periodontal tissues, and gingival tissues. The progressive strides achieved in the realm of bioprinting hold the potential to not only enhance the quality of life but also to catalyze transformative shifts within the domains of medical and dental practices. Full article

The extraction of impacted third molars is a common but potentially complication-prone oral surgical procedure. Wound healing plays a vital role in preventing complications. This scoping review aimed to assess the clinical and microbiological aspects of various suture materials and cyanoacrylates. Unlike existing studies, we included more articles and comprehensively compared suture materials. Articles published in languages other than English; duplicate studies; studies deemed irrelevant for the specific research questions, including those analyzing different supplementary treatments or not corresponding to the abstract’s content; ex vivo or experimental animal studies; studies lacking approval from an ethics committee; and narrative reviews, systematic reviews, or systematic and meta-analysis reviews were excluded. Thus, only 17 studies, published between 2000 and 2023, were included in the search. Suture techniques varied among surgeons, with debates on primary and secondary closure methods. A comparison of different suture materials and their effects on wound healing, infection rates, and other factors was described. Cyanoacrylate has also been used as an alternative to traditional sutures. Microbiological analysis showed varying bacterial adhesion based on the suture material, with silk sutures retaining more microbes than PTFE sutures. Clinical assessments have revealed differing inflammatory responses that affect wound healing and complications. Cyanoacrylate has emerged as a promising alternative to traditional sutures, owing to its rapid polymerization and early healing. However, the choice of suture material in impacted third molar surgery remains controversial, considering microbiological factors and clinical outcomes. More extensive randomized clinical trials are required to better understand the effect of suture materials on surgical outcomes and potential improvements. This study could enhance the safety and effectiveness of this common oral surgical procedure. Full article

Topical wound infections create the ideal conditions for microbial colonization and growth in terms of moisture, temperature, and nutrients. When they are not protected, numerous types of bacteria from the internal microbiota and the external environment may colonize them, creating a polymicrobial population. Treatment of these wounds often necessitates the use of antibiotics that may have systemic harmful effects. Unlike antibiotics, topical antiseptics exhibit a wider range of activity and reduced systemic toxicity and resistance. In order to address this issue, we developed an antiseptic Chitosan-Poly (hexamethylene) Biguanide (CS-PHMB) hydrogel. The prepared hydrogel was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). SEM images showed the smooth morphology and characteristic FTIR peaks of PHMB and confirmed the incorporation of the antiseptic into the chitosan (CS) hydrogel. A Water Vapor Permeation Rate study confirms the moisture retention ability of the CS-PHMB hydrogel. Rheological studies proved the gel strength and temperature stability. The prepared hydrogel inhibited the growth of S. aureus, P. aeruginosa, E. coli, methicillin-resistant Staphylococcus aureus (MRSA), and K. pneumoniae, which confirms its antibacterial properties. It also inhibited biofilm formation for S. aureus and E. coli. CS-PHMB hydrogel is also found to be hemo- and cytocompatible in nature. Thus, the developed CS-PHMB hydrogel is a very potent candidate to be used for treating infectious topical wounds with low systemic toxicity. Full article

Neurological injuries have poor prognoses with serious clinical sequelae. Stem cell transplantation enhances neural repair but is hampered by low graft survival (<ca. 5%), necessitating the development of approaches to enhance post-transplant cell viability. Intracerebral injection exerts high mechanical forces on transplant cells with risks of haemorrhage/infection. Transplant cell sprays can offer a non-invasive alternative. This study has assessed if the addition of protective, encapsulating polymer hydrogels to a cell spray format is feasible. Hydrogels (0.1% (1 mg/mL), 0.3% and 0.6% type I rat tail collagen) were trialled for spray deliverability. Cell-enriched hydrogels (containing mouse cortical astrocytes) were sprayed onto culture substrates. Astrocyte viability, cell-specific marker expression, morphology and proliferation were assessed at 24 h and 72 h post spraying. Intra-gel astrocytes and hydrogels could be co-stained using a double immunocytological technique (picrosirius red (PR)/DAB-peroxidase co-labelling). Astrocyte viability remained high post spraying with hydrogel encapsulation (>ca. 80%) and marker expression/proliferative potential of hydrogel-sprayed astrocytes was retained. Combining a cell spray format with polymer encapsulation technologies could form the basis of a non-invasive graft delivery method, offering potential advantages over current cell delivery approaches. Full article

The delivery of nucleosides represents an interesting research trend in recent years due to their application in various viral infections. The main aims of this study were to develop and to characterize polyurethane particles that are intended to be used for the transport of nucleosides. Three samples have been prepared using aliphatic diisocyanates, a mixture of polyethylene glycol, polycaprolactone, and diols, respectively. The samples were characterized through refractivity measurements, drug loading efficacy, release and penetration rate investigations, FTIR and Raman spectroscopy, thermal analyses, Zetasizer, SEM, HDFa cells viability, and irritation tests on mice skin. The results indicate the obtaining of particles with sizes between 132 and 190 nm, positive Zeta potential values (28.3–31.5 mV), and a refractivity index around 1.60. A good thermal stability was found, and SEM images show a medium tendency to agglomerate. The samples’ color, pH, and electrical conductivity have changed only to a small extent over time, and the evaluations indicate an almost 70% encapsulation efficacy, a prolonged release, and that around 70% of particles have penetrated an artificial membrane in the first 24 h. The synthesized products should be tested in further clinical trials, and the current tests on cell cultures and mice skin revealed no side effects. Full article

Nano-micelles are self-assembling colloidal dispersions applied to enhance the anticancer efficacy of chemotherapeutic agents. In this study, the conjugate of quarternized chitosan and vanillin imine (QCS-Vani imine) was synthesized using the reaction of a Schiff base characterized by proton-NMR (¹HNMR), UV-Vis spectroscopy, and FT-IR. The critical micelle concentration (CMC), particle size, and zeta potential of the resulting product were determined. The QCS-Vani imine conjugate was used as a carrier for the development of curcumin-loaded nano-micelles, and their entrapment efficiency (%EE), drug-loading capacity (%LC) and in vitro release were investigated using HPLC analysis. Moreover, the nano-micelles containing curcumin were combined with various concentrations of cisplatin and evaluated for a possible anticancer synergistic effect. The anticancer activity was evaluated against lung cancer A549 and mouse fibroblast L929 cell lines. The percent yield (%) of the QCS-Vani imine conjugate was 93.18%. The curcumin-loaded QCS-Vani imine nano-micelles were characterized and found to have a spherical shape (by TEM) with size < 200 nm (by DLS) with high %EE up to 67.61% and %LC up to 6.15 ± 0.41%. The loaded lyophilized powder of the nano-micelles was more stable at 4 °C than at room temperature during 120 days of storage. pH-sensitive release properties were observed to have a higher curcumin release at pH 5.5 (cancer environment) than at pH 7.4 (systemic environment). Curcumin-loaded QCS-Vani imine nano-micelles showed higher cytotoxicity and selectivity toward lung cancer A549 cell lines and exhibited lower toxicity toward the normal cell (H9C2) than pure curcumin. Moreover, the curcumin-loaded QCS-Vani imine nano-micelles exhibited an enhanced property of inducing cell cycle arrest during the S-phase against A549 cells and showed prominently induced apoptosis in lung cancer cells compared to that with curcumin. The co-treatment of cisplatin with curcumin-loaded QCS-Vani imine nano-micelles presented an enhanced anticancer effect, showing 8.66 ± 0.88 μM as the IC₅₀ value, in comparison to the treatment with cisplatin alone (14.22 ± 1.01 μM). These findings suggest that the developed QCS-Vani imine nano-micelle is a potential drug delivery system and could be a promising approach for treating lung cancer in combination with cisplatin. Full article

Cotton and polyamide 6,6 fabrics coated with chitosan, a natural biopolymer, have been tested against two different bacteria strains: Staphylococcus aureus as Gram-positive bacterium and Escherichia coli as Gram-negative bacterium. Using the ASTM standard method (Standard Test Method for Determining the Antimicrobial Activity of Antimicrobial Agents Under Dynamic Contact Conditions) for antibacterial testing, the treated fabrics is contacted for 1 h with the bacterial inoculum, the present study aims to investigate the possibility to reach interesting results considering shorter contact times. Moreover, the antibacterial activity of chitosan-treated fibers dyed with a natural dye, Carmine Red, was evaluated since chitosan has an interesting property that favors the attachment of the dye to the fiber (cross-linking ability). Finally, fabric samples were tested after washing cycles to verify the resistance of the dye and if the antibacterial property was maintained. Full article

Electroactive polymer–metal composites (EAPMCs) have gained significant attention in tissue engineering owing to their exceptional mechanical and electrical properties. EAPMCs develop by combining an electroactive polymer matrix and a conductive metal. The design considerations include choosing an appropriate metal that provides mechanical strength and electrical conductivity and selecting an electroactive polymer that displays biocompatibility and electrical responsiveness. Interface engineering and surface modification techniques are also crucial for enhancing the adhesion and biocompatibility of composites. The potential of EAPMC-based tissue engineering revolves around its ability to promote cellular responses, such as cell adhesion, proliferation, and differentiation, through electrical stimulation. The electrical properties of these composites can be used to mimic natural electrical signals within tissues and organs, thereby aiding tissue regeneration. Furthermore, the mechanical characteristics of the metallic components provide structural reinforcement and can be modified to align with the distinct demands of various tissues. EAPMCs have extraordinary potential as regenerative biomaterials owing to their ability to promote beneficial effects in numerous electrically responsive cells. This study emphasizes the characteristics and applications of EAPMCs in tissue engineering. Full article

The goal of this article was to assess the effect of modified triple-layer application (MTLA) in conjunction with the active bonding technique on the bond strength of four adhesive systems to dentinal substrate. The adhesives tested were Prime&Bond Universal (PBU), OptiBond Universal (OBU), OptiBond FL (OBFL), and Clearfil SE (CSE). The adhesives were applied according to the following strategies: single active application (A) and triple adhesive layer application including Active–Passive–Passive (APP); AAP; and AAA. The micro-tensile bond strength test was evaluated following 24 h or 6 months of storage. The composite–dentin interface morphology was investigated using scanning electron microscopy. The data were statistically analyzed with a significance level of α = 0.05. At 24 h of aging, all of the factors tested were not significant (p > 0.05) for CSE. For OBFL, OBU, and PBU, statistically higher values were observed for the A technique (p < 0.05). Plus, there were no significant variances between the APP, AAP, and AAA techniques (p > 0.05) for OBFL and PBU. However, for OBU, there were no significant differences between the A and AAA techniques (p > 0.05). After 6 months of aging, the A technique showed statistically higher values when compared to the other techniques (p < 0.01), except for OBFL, where the A and AAA techniques showed promising outcomes. When comparing the bond strength values of 24 h and 6 months, only for PBU, all of the techniques used resulted in bond strength stability over time (p > 0.05). Thicker adhesive layers were observed when MTLA was applied. Only the OBFL adhesive showed the formation of resin tags in all of the modalities tested. The bonding performances of the different application techniques used were material-dependent. Full article

Achieving lightweight, high-strength, and biocompatible composites is a crucial objective in the field of tissue engineering. Intricate porous metallic structures, such as lattices, scaffolds, or triply periodic minimal surfaces (TPMSs), created via the selective laser melting (SLM) technique, are utilized as load-bearing matrices for filled ceramics. The primary metal alloys in this category are titanium-based Ti6Al4V and iron-based 316L, which can have either a uniform cell or a gradient structure. Well-known ceramics used in biomaterial applications include titanium dioxide (TiO₂), zirconium dioxide (ZrO₂), aluminum oxide (Al₂O₃), hydroxyapatite (HA), wollastonite (W), and tricalcium phosphate (TCP). To fill the structures fabricated by SLM, an appropriate ceramic is employed through the spark plasma sintering (SPS) method, making them suitable for in vitro or in vivo applications following minor post-processing. The combined SLM-SPS approach offers advantages, such as rapid design and prototyping, as well as assured densification and consolidation, although challenges persist in terms of large-scale structure and molding design. The individual or combined application of SLM and SPS processes can be implemented based on the specific requirements for fabricated sample size, shape complexity, densification, and mass productivity. This flexibility is a notable advantage offered by the combined processes of SLM and SPS. The present article provides an overview of metal–ceramic composites produced through SLM-SPS techniques. Mg-W-HA demonstrates promise for load-bearing biomedical applications, while Cu-TiO₂-Ag exhibits potential for virucidal activities. Moreover, a functionally graded lattice (FGL) structure, either in radial or longitudinal directions, offers enhanced advantages by allowing adjustability and control over porosity, roughness, strength, and material proportions within the composite. Full article

Additively manufactured (AM) porous titanium implants may have an increased risk of implant-associated infection (IAI) due to their huge internal surfaces. However, the same surface, when biofunctionalized, can be used to prevent IAI. Here, we used a rat implant infection model to evaluate the biocompatibility and infection prevention performance of AM porous titanium against bioluminescent methicillin-resistant Staphylococcus aureus (MRSA). The specimens were biofunctionalized with Ag nanoparticles (NPs) using plasma electrolytic oxidation (PEO). Infection was initiated using either intramedullary injection in vivo or with in vitro inoculation of the implant prior to implantation. Nontreated (NT) implants were compared with PEO-treated implants with Ag NPs (PT-Ag), without Ag NPs (PT) and infection without an implant. After 7 days, the bacterial load and bone morphological changes were evaluated. When infection was initiated through in vivo injection, the presence of the implant did not enhance the infection, indicating that this technique may not assess the prevention but rather the treatment of IAIs. Following in vitro inoculation, the bacterial load on the implant and in the peri-implant bony tissue was reduced by over 90% for the PT-Ag implants compared to the PT and NT implants. All infected groups had enhanced osteomyelitis scores compared to the noninfected controls. Full article

Challenges associated with drug-releasing stents used in percutaneous transluminal coronary angioplasty (PTCA) encompass allergic reactions, prolonged endothelial dysfunction, and delayed stent clotting. Although absorbable stents made from magnesium alloys seem promising, fast in vivo degradation and poor biocompatibility remain major challenges. In this study, zirconia (ZrO₂) layers were used as the foundational coat, while calcium phosphate (CaP) served as the surface layer on unalloyed magnesium specimens. Consequently, the corrosion current density was decreased to 3.86, from 13.3 μA/cm². Moreover, a heparin-controlled release mechanism was created by co-depositing CaP, gelatin (Gel), and heparin (Hep) on the specimens coated with CaP/ZrO₂, thereby boosting magnesium’s blood compatibility and prolonging the heparin-releasing time. Techniques like X-ray diffractometry (XRD), focused ion beam (FIB) system, toluidine blue testing, UV–visible spectrometry, field emission scanning electron microscopy (FESEM), and surrogate tests for endothelial cell viability were employed to examine the heparin-infused coatings. The drug content rose to 484.19 ± 19.26 μg/cm² in multi-layered coatings (CaP-Gel-Hep/CaP-Hep/CaP/ZrO₂) from 243.56 ± 55.18 μg/cm² in a single layer (CaP-Hep), with the controlled release spanning beyond 28 days. Also, cellular viability assessments indicated enhanced biocompatibility of the coated samples relative to those without coatings. This suggests the potential of magnesium samples after coating ZrO₂ and CaP with Gel as candidates for porous biodegradable stents or even scaffolds in biomedical applications. Full article

The process of tissue regeneration requires the utilization of a scaffold, which serves as a structural framework facilitating cellular adhesion, proliferation, and migration within a physical environment. The primary aim of scaffolds in tissue engineering is to mimic the structural and functional properties of the extracellular matrix (ECM) in the target tissue. The construction of scaffolds that accurately mimic the architecture of the extracellular matrix (ECM) is a challenging task, primarily due to the intricate structural nature and complex composition of the ECM. The technique of decellularization has gained significant attention in the field of tissue regeneration because of its ability to produce natural scaffolds by removing cellular and genetic components from the extracellular matrix (ECM) while preserving its structural integrity. The present study aims to investigate the various decellularization techniques employed for the purpose of isolating the extracellular matrix (ECM) from its native tissue. Additionally, a comprehensive comparison of these methods will be presented, highlighting their respective advantages and disadvantages. The primary objective of this study is to gain a comprehensive understanding of the anatomical and functional features of the native liver, as well as the prevalence and impact of liver diseases. Additionally, this study aims to identify the limitations and difficulties associated with existing therapeutic methods for liver diseases. Furthermore, the study explores the potential of tissue engineering techniques in addressing these challenges and enhancing liver performance. By investigating these aspects, this research field aims to contribute to the advancement of liver disease treatment and management. Full article

Biological augmentation of bony defects in weight-bearing areas of both the acetabulum and the femur remains challenging. The calcium-silicate-based ceramic Baghdadite is a very interesting material to be used in the field of revision total hip arthroplasty for the treatment of bony defects in weight-bearing and non-weight-bearing areas alike. The aim of this study was to investigate the biocompatibility of Baghdadite utilizing an osteoblast-like, human osteosarcoma cell line (MG-63) and the human monocytic leukemia-derived cell line (THP-1). THP-1-derived macrophages and MG-63 were indirectly exposed to Baghdadite for 7 days using a transwell system. Viability was assessed with MTT assay and pH analysis. To investigate proliferation rate, both cell lines were labelled using CFSE and flow cytometrically analyzed. ELISA was used to measure the secretion of IL-1ß, IL-6 and TNFα. The investigation of viability, while showing a slight difference in optical density for the MTT assays in MG-63 cells, did not present a meaningful difference between groups for both cell lines. The comparison of pH and the proportion of living cells between groups did not present with a significant difference for both THP-1 and MG-63. Baghdadite did not have a relevant impact on the proliferation rate of the investigated cell lines. Mean fluorescence intensity was calculated between groups with no significant difference. Baghdadite exerted a proinflammatory effect, which could be seen in an upregulated production of TNFα in macrophages. Production of IL-1ß and IL-6 was not statistically significant, but the IL-6 ELISA showed a trend to an upregulated production as well. A similar effect on MG-63 was not observed. No relevant cytotoxicity of Baghdadite ceramics was encountered. Baghdadite ceramics exhibit a proinflammatory potential by significantly increasing the secretion of TNFα in THP-1-derived macrophages. Whether this proinflammatory potential results in a clinically relevant effect on osteointegration is unclear and requires further investigation. Baghdadite ceramics provide an interesting alternative to conventional bone substitutes and should be further investigated in a biomechanical and in vivo setting. Full article

For patients with severe burns that consist of contractures induced by fibrous scar tissue formation, a graft must adhere completely to the wound bed to enable wound healing and neovascularization. However, currently available grafts are insufficient for scar suppression owing to their nonuniform pressure distribution in the wound area. Therefore, considering the characteristics of human skin, which is omnidirectionally stretched via uniaxial stretching, we proposed an auxetic skin scaffold with a negative Poisson’s ratio (NPR) for tight adherence to the skin scaffold on the wound bed site. Briefly, a skin scaffold with the NPR effect was fabricated by creating a fine pattern through 3D printing. Electrospun layers were also added to improve adhesion to the wound bed. Fabricated skin scaffolds displayed NPR characteristics (−0.5 to −0.1) based on pulling simulation and experiment. Finger bending motion tests verified the decreased marginal forces (<50%) and deformation (<60%) of the NPR scaffold. In addition, the filling of human dermal fibroblasts in most areas (>95%) of the scaffold comprising rarely dead cells and their spindle-shaped morphologies revealed the high cytocompatibility of the developed scaffold. Overall, the developed skin scaffold may help reduce wound strictures in the joints of patients with burns as it exerts less pressure on the wound margin. Full article

The type of implant-abutment connection is one of the factors influencing the distribution of occlusal forces. This study aims to investigate the biomechanical performance of the mandibular all-on-4 treatment with different implant–abutment connections. Two connection types with 30° abutments and 18-mm implant fixtures were chosen for the posterior implants of the all-on-4 assembly. For the external hexagon connection (EHC) group, the implants with 4 mm in diameter were used. For the internal hexagon connection (IHC) group, we selected implants with 4.3 mm in diameter. A vertical force of 190 N was applied to the cantilever region. The FEA results indicated that the most stressed region in the two groups was prosthetic screws, followed by multi-unit abutments (MUAs). The lowest values of von Mises stress were both observed on the bone. The peak stress value of the implant screw and implant fixture in the EHC group were 37.75% and 33.03% lower than the IHC group, respectively. For stress distribution patterns, the load force tended to be concentrated at locations where components were interconnected. The EHC and IHC are clinically durable under the tested loading conditions, but the prosthetic screws and MUAs can be the weak point on the posterior implant within the mandibular all-on-four assembly. The peak stress values of implant screw and implant fixture in the EHC groups were lower than the IHC group. Full article

Superparamagnetic iron oxide nanoparticles (SPIONs) have garnered significant attention in the medical sector due to their exceptional superparamagnetic properties and reliable tracking capabilities. In this study, we investigated the immunotoxicity of SPIONs with a modified surface to enhance hydrophilicity and prevent aggregate formation. The synthesized SPIONs exhibited a remarkably small size (~4 nm) and underwent surface modification using a novel “haircut” reaction strategy. Experiments were conducted in vitro using a human monocytic cell line (THP-1). SPIONs induced dose-dependent toxicity to THP-1 cells, potentially by generating ROS and initiating the apoptotic pathway in the cells. Concentrations up to 10 μg/mL did not affect the expression of Nrf2, HO-1, NF-κB, or TLR-4 proteins. The results of the present study demonstrated that highly hydrophilic SPIONs were highly toxic to immune cells; however, they did not activate pathways of inflammation and immune response. Further investigation into the mechanisms of cytotoxicity is warranted to develop a synthetic approach for producing effective, highly hydrophilic SPIONs with little to no side effects. Full article

Objective: Our aim was to evaluate the capacity of the human salivary histatin-1-functionalized methacrylic gelatin scaffold to control osteochondral tissue regeneration and repair in vivo in rabbits with major temporomandibular joint dimensional abnormalities. Materials and Methods: In order to compare human salivary histatin-1-functionalized methacrylic gelatin scaffolds to the Blank and Gel-MA hydrogel groups, scaffolds were implanted into osteochondral lesions of a critical size (3 × 3 mm) in the anterior region of the condyle of the temporomandibular joint in New Zealand white rabbits. At 4 weeks after implantation, the repair was evaluated using macroscopic examination, histology, and micro-CT analysis. Results: In the comparison of the composite scaffold group with the Blank and Gel-MA groups, analysis of the healed tissue revealed an improved macroscopic appearance in the composite scaffold group. Regeneration was induced by host cell migration in the Hst1/Gel-MA scaffold group. Conclusions: The current study offers a viable method for in vivo cartilage repair that does not require cell transplantation. Future clinical applications of this strategy’s optimization have many potential advantages. Full article

This study explored the feasibility of using fish skin bandages as a therapeutic option for third-degree skin burns. Following the California wildfires, clinical observations of animals with third-degree skin burns demonstrated increased comfort levels and reduced pain when treated with tilapia fish skin. Despite the promises of this therapy, there are few studies explaining the healing mechanisms behind the application of tilapia fish skin. In this study, mice with third-degree burns were treated with either a hydrocolloid adhesive bandage (control) (n = 16) or fish skin (n = 16) 7 days post-burn. Mice were subjected to histologic, hematologic, molecular, and gross evaluation at days 7, 16, and 28 post-burn. The fish skin offered no benefit to overall wound closure compared to hydrocolloids. Additionally, we detected no difference between fish skin and control treatments in regard to hypermetabolism or hematologic values. However, the fish skin groups exhibited 2 times more vascularization and 2 times higher expression of antimicrobial defensin peptide in comparison to controls. Proteomic analysis of the fish skin revealed the presence of antimicrobial peptides. Collectively, these data suggest that fish skin can serve as an innovative and cost-effective therapeutic alternative for burn victims to facilitate vascularization and reduce bacterial infection. Full article

This study assessed the antibacterial characteristics of the dentin/material interface and dentin surfaces exposed to experimental hydraulic calcium silicate cement (HCSC) with or without bioactive glass (BG) replacement (20% or 40%) or mixed with a silver nanoparticle (SNP) solution (1 or 2 mg/mL), and Biodentine, TotalFill BC RRM putty and Intermediate Restorative Material (IRM). Human root dentin segments with test materials were assessed at 1 or 28 days. In one series, the specimens were split to expose the dentin and material surfaces. A 24 h direct contact test was conducted against three-day established Enterococcus faecalis and Pseudomonas aeruginosa monospecies biofilms. In another series, the dentin/material interface of intact specimens was exposed to biofilm membranes for 3 days and the antibacterial activity was assessed via confocal microscopy. The interface was additionally characterised. All one-day material and dentin surfaces were antibacterial. Dentin surfaces exposed to HCSC with 40% BG-replacement, Biodentine and IRM had decreased antibacterial properties compared to those of the other cements. The HCSC mixed with a 2 mg/mL SNP solution had the highest antimicrobial effect in the confocal assay. The interfacial characteristics of HCSCs were similar. The test materials conferred antibacterial activity onto the adjacent dentin. The BG reduced the antibacterial effect of dentin exposed to HCSC; a 2 mg/mL SNP solution increased the antibacterial potential for longer interaction periods (three-day exposure). Full article

In this work, we have developed and characterized a ceramic composite based on a core of directionally solidified calcium zirconate-calcium stabilized zirconia (CZO-CSZ) eutectic composite coated with a bioactive glass-ceramic. The aim is to research new orthopedic implants as an alternative to conventional 3Y-TZP bioinert ceramics. The CZO-CSZ eutectic rods were grown from the melt of rods of CaO-ZrO₂ in the eutectic composition using the laser floating zone technique (LFZ). The mechanical results indicated that directional eutectics prepared with this technique exhibited good mechanical strength and significant hardness and toughness. The LFZ technique was also used to melt the bioactive coating previously placed by dip coating on the CZO-CSZ rod surface. Depending on the thickness of the coating and the applied laser power, an alloying or coating process was achieved. In the first case, the coating was diluted with the surface of the eutectic cylinder, leading to the segregation of the calcium zirconate and zirconia phases and the formation of a bioactive phase embedding zirconia particles. In the second case, a layer of ceramic glass was formed, well attached to the eutectic cylinder. These layers were both studied from the microstructural and bioactivity points of view. Full article

Silver nanoparticles (AgNPs) have emerged as a promising tool for cancer treatment due to their unique physicochemical and biological properties. However, their clinical applications are limited by their potential cytotoxicity caused due to oxidation stress and non-specific cellular uptake pathways. To overcome these barriers, surface modifications of AgNPs have been proposed as an effective strategy to enhance their biocompatibility and specificity toward cancer cells. In this study, AgNPs were synthesised using the chemical reduction method and subsequently conjugated with various capping agents such as Polyvinylpyrrolidone (PVP) and Bovine Serum Albumin (BSA). Further, this study involves the synthesis of liposomes by using dipalmitoyl phosphatidylcholine lipid (DPPC) and cholesterol to increase the biocompatibility and bioavailability of AgNPs to MCF-7 breast cancer cells. In vitro, cytotoxicity studies were performed to determine which surface modification method exhibited the highest cytotoxic effect on the MCF-7 breast cancer cells, which was determined through the MTT assay. The AgNPs conjugated with BSA exhibited the highest cytotoxicity at the lowest dosage, with an IC₅₀ of 2.5 μL/mL. The BSA-AgNPs induced a dose-dependent rise in cytotoxicity through the enhancement of nucleophilic dissolution of the AgNPs in cancer cells. In comparison, the unmodified AgNPs had an IC₅₀ value of 3.0 μL/mL, while the PVP-modified AgNPs had an IC₅₀ of 4.24 μL/mL. AgNPs encapsulated in liposomes had an IC₅₀ value of 5.08 μL/mL, which shows that the encapsulation of AgNPs in liposomes controls their entry into cancer cells. The findings of this research have provided insights into the potential use of surface-modified AgNPs and liposomal encapsulated AgNPs as novel therapeutic tools to overcome the conventional treatment limitations of breast cancer cells. Full article

This laboratory study aimed to evaluate the effect of different surface patterns using femtosecond laser treatment on the enclosed mold shear bond strength (EM-SBS) of resin composite to zirconia (ZrO₂) surfaces and to contrast it with the widely used tribochemical silica coating (TBC) surface conditioning method. A set of fifteen rectangular ZrO₂ blocks were randomly divided into five groups according to surface pretreatment: Control G₀—no treatment; G₁—TBC with silane application; G₂—femtosecond laser irradiation with horizontal lines 30 µm apart; _G3—femtosecond laser irradiation with horizontal lines 15 µm apart; and G₄—femtosecond laser irradiation with cross lines 30 µm apart. The pretreated surfaces were characterized by a surface profilometer, tensiometer and scanning electron microscope. The EM-SBS of resin composite stubs to ZrO₂ was measured followed by fractographic analysis. The surface roughness and water contact angle were observed to be statistically higher among the femtosecond laser groups compared to the TBC and control groups. The G₄ group exhibited the highest EM-SBS among all the groups, irrespective of the ageing conditions used. At the end of 5000 thermocycles, G₄ exhibited EM-SBS of 14.05 ± 4.21 MPa compared to 13.80 ± 3.01 MPa in G₁ and 5.47 ± 0.97 MPa in G₀. The two-way ANOVA revealed a significant effect of both study groups and ageing conditions on the EM-SBS (p < 0.001). Utilization of femtosecond laser technology holds promise as a potential and alternative mechanical retention approach for enhancing the bonding strength of the resin composite to ZrO₂. Full article

Biocompatibility and biomineralization of root canal dressings are important requirements for periapical healing. This study evaluated the inflammatory response, biomineralization and tissue repair by collagen fiber maturation in the subcutaneous tissue of rats. Eighteen Wistar rats (n = 6) received subcutaneous implants: calcium hydroxide + propylene glycol [CH+P], calcium hydroxide + propylene glycol + iodoform [CH+P+I], iodoform + carbowax [I+Cwax] and carbowax [Cwax]. Extra empty tubes were used as a control [C]. After 7, 15 and 30 days, the implants were removed with surrounding tissue for staining of hematoxylin-eosin, Von Kossa, picrosirius red and without staining for analysis under polarized light. Results were analyzed via Kruskal–Wallis followed by Dunn testing for nonparametric data and ANOVA followed by a Tukey post hoc test for parametric data (p < 5%). At 7 days, all groups showed a moderate inflammatory reaction and thick fibrous capsule, except the [Cwax] group, with a severe inflammatory infiltrate (p < 0.05). After 15 days, all groups but control had a decrease in inflammatory response. At 30 days, all groups presented a mild reaction and thin fibrous capsule (p > 0.05). Only groups containing calcium hydroxide were found to be positive using Von Kossa staining and polarized light in all periods. At 7 days, all groups showed a higher proportion of immature fibers. At 15 days, the [CH+P] and [Cwax] groups increased their proportion of mature/immature fibers. At 30 days, only the [CH+P] group presented a significant prevalence of mature collagen fibers (p < 0.05). All groups showed biocompatibility, but only groups containing calcium hydroxide induced biomineralization. The addition of iodoform delayed tissue healing. Full article

The development of multifunctional materials has been expected in dentistry. This study investigated the effects of a novel universal bond containing a bioactive monomer, calcium 4-methacryloxyethyl trimellitic acid (CMET), on odontoblast differentiation in vitro. Eluates from bioactive universal bond with CMET (BA (+), BA bond), bioactive universal bond without CMET (BA (−)), and Scotchbond Universal Plus adhesive (SC, 3M ESPE, USA) were added to the culture medium of the rat odontoblast-like cell line MDPC-23. Then, cell proliferation, differentiation, and mineralization were examined. Statistical analyses were performed using a one-way ANOVA and Tukey’s HSDtest. The cell counting kit-8 assay and alkaline phosphatase (ALP) assay showed that cell proliferation and ALP were significantly higher in the 0.5% BA (+) group than in the other groups. In a real-time reverse-transcription polymerase chain reaction, mRNA expression of the odontogenic markers, dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), was significantly higher in the 0.5% BA (+) group than in the BA (−) and SC groups. Calcific nodule formation in MDPC-23 cells was accelerated in the BA (+) group in a dose-dependent manner (p < 0.01); however, no such effect was observed in the BA (−) and SC groups. Thus, the BA bond shows excellent potential for dentin regeneration. Full article

Bone tissue engineering seeks biomaterials that enable cell migration, angiogenesis, matrix deposition, and tissue regeneration. Blood concentrates like platelet-rich fibrin (L-PRF) offer a cost-effective source of cells and growth factors to enhance healing. The present study aimed to evaluate heated serum albumin with liquid PRF (Alb-PRF) and L-PRF clinically and biochemically after placement in dental sockets following mandibular third molar extraction. In a controlled, split-mouth study involving 10 volunteers, 20 extracted molars were treated with either Alb-PRF or L-PRF. Post-extraction, pain, trismus, infection presence, and swelling were measured. The concentrations of different analytes in the surgical sites were also examined. The data were statistically analyzed, with significance defined at p < 0.05 (t-test). No significant difference was noted between the groups for pain and trismus, but Alb-PRF showed a significant reduction in swelling on day seven. The Alb-PRF group showed lower levels of pro-inflammatory cytokines (GM-CSF, IL-1b, IL-6, IFNy, IL-8, IL-15, RANTES, and MIP-1a) after seven days, with only higher expressions of MIP-1b, IL-1b, and MCP-1 found in the L-PRF group. Differences were observed in the release of analytes between L-PRF and Alb-PRF, with Alb-PRF significantly reducing edema after seven days. Alb-PRF reduced edema, while L-PRF increased inflammatory cytokines. When compared to L-PRF, Alb-PRF reduced edema and the release of inflammatory cytokines, suggesting promising effects in socket healing while underscoring the role of growth factors and cytokines in potential applications of blood concentrates. Full article

Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications. Full article

Platelet-rich fibrin (PRF) is a second-generation blood concentrate that serves as an autologous approach for both soft and hard tissue regeneration. It provides a scaffold for cell interaction and promotes the local release of growth factors. PRF has been investigated as an alternative to bone tissue therapy, with the potential to expedite wound healing and bone regeneration, though the mechanisms involved are not yet fully understood. This review aims to explore the in vitro evidence of PRF’s effects on the behavior of mineralizing cells related to bone tissue regeneration. A systematic electronic search was conducted up to August 2023, utilizing three databases: PubMed, Web of Science, and Scopus. A total of 76 studies were selected, which presented in vitro evidence of PRF’s usefulness, either alone or in conjunction with other biomaterials, for bone tissue treatment. PRF membranes’ influence on the proliferation, differentiation, and mineralization of bone cells is linked to the constant release of growth factors, resulting in changes in crucial markers of bone cell metabolism and behavior. This further reinforces their therapeutic potential in wound healing and bone regeneration. While there are some notable differences among the studies, the overall results suggest a positive effect of PRF on cell proliferation, differentiation, mineralization, and a reduction in inflammation. This points to its therapeutic potential in the field of regenerative medicine. Collectively, these findings may help enhance our understanding of how PRF impacts basic physiological processes in bone and mineralized tissue. Full article