Spatiotemporally Controlled Release of Etamsylate from Bioinspired Peptide-Functionalized Nanoparticles Arrests Bleeding Rapidly and Improves Clot Stability in a Rabbit Internal Hemorrhage Model.

Achieving rapid clotting and clot stability are important unmet goals of clinical management of noncompressible hemorrhage. This study reports the development of a spatiotemporally controlled release system of an antihemorrhagic drug, etamsylate, in the management of internal hemorrhage. Gly-Arg-Gly-Asp-Ser (GRGDS) peptide-functionalized chitosan nanoparticles, with high affinity to bind with the GPIIa/IIIb receptor of activated platelets, were loaded with the drug etamsylate (etamsylate-loaded GRGDS peptide-functionalized chitosan nanoparticles; EGCSNP). Peptide conjugation was confirmed by LCMS, and the delivery system was characterized by DLS, SEM, XRD, and FTIR. In vitro study exhibited 90% drug release till 48 h fitting into the Weibull model. Plasma recalcification time and prothrombin time tests of GRGDS-functionalized nanoparticles proved that clot formation was 1.5 times faster than nonfunctionalized chitosan nanoparticles. The whole blood clotting time was increased by 2.5 times over clot formed under nonfunctionalized chitosan nanoparticles. Furthermore, the application of rheometric analysis revealed a 1.2 times stiffer clot over chitosan nanoparticles. In an in vivo liver laceration rabbit model, EGCSNP spatially localized at the internal injury site within 5 min of intravenous administration, and no rebleeding was recorded up to 3 h. The animals survived for 3 weeks after the injury, indicating the strong potential of the system for the management of noncompressible hemorrhage.

Unveiling advanced strategies for therapeutic stem cell interventions in severe burn injuries: a comprehensive review.

This comprehensive review explores the complex terrain of stem cell therapies as a potential therapeutic frontier in the healing of complicated burn wounds. Serious tissue damage, impaired healing processes, and possible long-term consequences make burn wounds a complex problem. An in-depth review is required since, despite medical progress, existing methods for treating severe burn wounds have significant limitations. Burn wounds are difficult to heal because they cause extensive tissue damage. The challenges of burn injury-induced tissue regeneration and functional recovery are also the subject of this review. Although there is a lot of promise in current stem cell treatments, there are also some limitations with scalability, finding the best way to transport the cells, and finding consistent results across different types of patients. To shed light on how to improve stem cell interventions to heal severe burn wounds, this review covers various stem cell applications in burn wounds and examines these obstacles. To overcome these obstacles, one solution is to enhance methods of stem cell distribution, modify therapies according to the severity of the burn, and conduct more studies on how stem cell therapy affects individual patients. Novel solutions may also be possible through the combination of cutting-edge technologies like nanotechnology and biotechnology. This review seeks to increase stem cell interventions by analyzing present challenges and suggesting strategic improvements. The goal is to provide a more effective and tailored way to repair serious burn wounds.

Stimulated Full-Thickness Cutaneous Wound Healing with Bioactive Dressings of Zinc and Cobalt Ion-Doped Bioactive Glass-Coated Eggshell Membranes in a Diabetic Rabbit Model.

Eggshell membrane-based biomedical applications have recently received great attention for their wound-healing properties. However, there are limited studies on diabetic wound healing. In this regard, we devised four types of composite eggshell membrane mats with nanoscale coatings of bioactive glass/Zn/Co-doped bioactive glass (ESM + BAG, ESM + ZnBAG, ESM + CoBAG, and ESM + ZnCoBAG) as wound-dressing materials for chronic nonhealing diabetic wounds. A detailed study of the physicochemical properties of the mats was conducted. In vitro studies demonstrated cytocompatibility and viability of human dermal fibroblasts on all four types of mats. The cells also attached finely on the mats with the help of cellular extensions, as evident from scanning electron microscopy (SEM) and rhodamine-phalloidin and Hoechst 33342 staining of cellular components. Endowed with bioactive properties, these mats influenced all aspects of full-thickness skin wound healing in diabetic animal model studies. All of the mats, especially the ESM + ZnCoBAG mat, showed the earliest wound closure, effective renewal, and restructuring of the extracellular matrix in terms of an accurate and timely accumulation of collagen, elastin, and reticulin fibers. Hydroxyproline and sulfated glycosaminoglycans were significantly (p < 0.01, p < 0.05) higher in ESM-ZnCoBAG-treated wounds in comparison to ESM-BAG-treated wounds, which suggests that these newly developed mats have potential as an affordable diabetic wound care solution in biomedical research.

Recent trends of stem cell therapies in The management of orthopedic surgical challenges.

Emerged health-related problems especially with increasing population and with the wider occurrence of these issues have always put the utmost concern and led medicine to outgrow its usual mode of treatment, to achieve better outcomes. Orthopedic interventions are one of the most concerning hitches, requiring advancement in several issues, that show complications with conventional approaches. Advanced studies have been undertaken to address the issue, among which stem cell therapy emerged as a better area of growth. The capacity of the stem cells to renovate themselves and adapt into different cell types made it possible to implement its use as a regenerative slant. Harvesting the stem cells, particularly mesenchymal stem cells is easier and can be further grown in vitro. In this review, we have discussed orthopedic-related issues including bone defects and fractures, non-unions, ligament and tendon injuries, degenerative changes, and associated conditions, which require further approaches to execute better outcomes, and the advanced strategies that can be tagged along with various ways of application of mesenchymal stem cells. It aims to objectify the idea of stem cells, with a major focus on the application of Mesenchymal stem cells (MSCs) from different sources in various orthopedic interventions. It also discusses the limitations, and future scopes for further approaches in the field of regenerative medicine. The involvement of mesenchymal stem cells may transition the procedures in orthopedic interventions from predominantly surgical substitution and reconstruction to bio-regeneration and prevention. Nevertheless, additional improvements and evaluations are required to explore the effectiveness and safety of mesenchymal stem cell treatment in orthopedic regenerative medicine.

Effects of the multiscale porosity of decellularized platelet-rich fibrin-loaded zinc-doped magnesium phosphate scaffolds in bone regeneration.

In recent years, metallic ion-doped magnesium phosphate (MgP)-based degradable bioceramics have emerged as alternative bone substitute materials owing to their excellent biocompatibility, bone-forming ability, bioactivity, and controlled degradability. Conversely, incorporating a biomolecule such as decellularized platelet-rich fibrin (d-PRF) on scaffolds has certain advantages for bone tissue regeneration, particularly in enhanced osteogenesis and angiogenesis. The present study focuses on the impact of d-PRF-loaded multiscale porous zinc-doped magnesium phosphate (Zn-MgP) scaffolds on biodegradability, biocompatibility, and bone regeneration. Scaffolds were fabricated through the powder-metallurgy route utilizing naphthalene as a porogen (porosity = 5-43%). With the inclusion of a higher porogen, a higher fraction of macro-porosity (>20 µm) and pore interconnectivity were observed. X-ray diffraction (XRD) studies confirmed the formation of the farringtonite phase. The developed scaffolds exhibited a minimum ultimate compressive strength (UCS) of 8.5 MPa (for 40 Naph), which lies within the range of UCS of the cancellous bone of humans (2-12 MPa). The in vitro assessment via immersion in physiological fluid yielded a higher deposition of the calcium phosphate (CaP) compound in response to increased macro-porosity and interconnectivity (40 Naph). Cytocompatibility assessed using MC3T3-E1 cells showed that the incorporation of d-PRF coupled with increased porosity resulted the highest cell attachment, proliferation, and viability. For further evaluation, the developed scaffolds were implanted in in vivo rabbit femur condylar defects. Radiography, SEM, OTC labelling, and histology analysis after 2 months of implantation revealed the better invasion of mature osteoblastic cells into the scaffolds with enhanced angiogenesis and superior and accelerated healing of bone defects in d-PRF-incorporated higher porosity scaffolds (40 Naph). Finally, it is hypothesized that the combination of d-PRF incorporation with multiscale porosity and increased interconnectivity facilitated better bone-forming ability, good biocompatibility, and controlled degradability within and around the Zn-doped MgP scaffolds.

Synergistic Improvement of Antibacterial and Osteogenic Differentiation of Thermomechanically Processed Mg-Zr-Sr-Ce Alloy: Insights into the Role of Precipitate Evolution Supported by AIMD Simulation Study.

In the present study, we have discussed the influence of forging temperature (623 K (FT623), 723 K (FT723) and 823 K (FT823)) on microstructure and texture evolution and its implication on mechanical behavior, in vitro-in vivo biocorrosion, antibacterial response, and cytocompatibility of microalloyed Mg-Zr-Sr-Ce alloy. Phase analysis, SEM, and TEM characterization confirm the presence of Mg12Ce precipitate, and its stability was further validated by performing ab initio molecular dynamic simulation study. FT723 exhibits strengthened basal texture, higher fraction of second phases, and particle-stimulated nucleation-assisted DRX grains compared to other two specimens, resulting in superior strength with comparable ductility. FT723 also exhibits superior corrosion resistance mainly due to the strengthened basal texture and lower dislocation density. All the specimens exhibit excellent antibacterial behavior with Gram-negative E. coli, Gram-positive Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. 100% reduction of bacterial growth is observed within 24 h of culture of the specimens. Cytocompatibility was determined by challenging specimen extracts with the MC3T3-E1 cell lines. FT723 specimen exhibits the highest cell proliferation and alkaline phosphatase activity (ALP) because of its superior corrosion resistance. The ability of the specimens to be used in orthopedic implant application was evaluated by in vivo study in rabbit femur. Neither tissue-related infection nor the detrimental effect surrounding the implant was confirmed from histological analysis. Significant higher bone regeneration surrounding the FT723 specimen was observed in SEM analysis and fluorochrome labeling. After 60 days, the FT723 specimen exhibits the highest bone formation, suggesting it is a suitable candidate for orthopedic implant application.

Biomaterials-Based Strategies to Enhance Angiogenesis in Diabetic Wound Healing.

Amidst the present healthcare issues, diabetes is unique as an emerging class of affliction with chronicity in a majority of the population. To check and control its effects, there have been huge turnover and constant development of management strategies, and though a bigger part of the health care area is involved in achieving its control and the related issues such as the effect of diabetes on wound healing and care and many of the works have reached certain successful outcomes, still there is a huge lack in managing it, with maximum effect yet to be attained. Studying pathophysiology and involvement of various treatment options, such as tissue engineering, application of hydrogels, drug delivery methods, and enhancing angiogenesis, are at constantly developing stages either direct or indirect. In this review, we have gathered a wide field of information and different new therapeutic methods and targets for the scientific community, paving the way toward more settled ideas and research advances to cure diabetic wounds and manage their outcomes.

Photo-Polymerizable Autologous Growth-Factor Loaded Silk-Based Biomaterial-Inks toward 3D Printing-Based Regeneration of Meniscus Tears.

Meniscus tears in the avascular region undergoing partial or full meniscectomy lead to knee osteoarthritis and concurrent lifestyle hindrances in the young and aged alike. Here they reported ingenious photo-polymerizable autologous growth factor loaded 3D printed scaffolds to potentially treat meniscal defects . A shear-thinning photo-crosslinkable silk fibroin methacrylate-gelatin methacrylate-polyethylene glycol dimethacrylate biomaterial-ink is formulated and loaded with freeze-dried growth factor rich plasma (GFRP) . The biomaterial-ink exhibits optimal rheological properties and shape fidelity for 3D printing. Initial evaluation revealed that the 3D printed scaffolds mimic mechanical characteristics of meniscus, possess favourable porosity and swelling characteristics, and demonstrate sustained GFRP release. GFRP laden 3D scaffolds are screened with human neo-natal stem cells in vitro and biomaterial-ink comprising of 25 mg mL-1 of GFRP (GFRP25) is found to be amicable for meniscus tissue engineering. GFRP25 ink demonstrated rigorous rheological compliance, and printed constructs demonstrated long term degradability (>6 weeks), GFRP release (>5 weeks), and mechanical durability (3 weeks). GFRP25 scaffolds aided in proliferation of seeded human neo-natal stem cellsand their meniscus-specific fibrochondrogenic differentiation . GFRP25 constructs show amenable inflammatory response in vitro and in vivo. GFRP25 biomaterial-ink and printed GFRP25 scaffolds could be potential patient-specific treatment modalities for meniscal defects.

Biomineralized fluorocanasite-reinforced biocomposite scaffolds demonstrate expedited osteointegration of critical-sized bone defects.

The development of patient-specific bone scaffolds that can expedite bone regeneration has been gaining increased attention, especially for critical-sized bone defects or fractures. Precise adaptation of the scaffold to the region of implantation and reduced surgery times are also crucial at clinical scales. To this end, bioactive fluorcanasite glass-ceramic microparticulates were incorporated within a biocompatible photocurable resin matrix following which the biocomposite resin precursor was 3D-printed with digital light processing method to develop the bone scaffold. The printing parameters were optimized based on spot curing investigation, particle size data, and UV-visible spectrophotometry. In vitro cell culture with MG-63 osteosarcoma cell lines and pH study within simulated body fluid demonstrated a noncytotoxic response of the scaffold samples. Further, the in vivo bone regeneration ability of the 3D-printed biocomposite bone scaffolds was investigated by implantation of the scaffold samples in the rabbit femur bone defect model. Enhanced angiogenesis, osteoblastic, and osteoclastic activities were observed at the bone-scaffold interface, while examining through fluorochrome labelling, histology, radiography, field emission scanning electron microscopy, and x-ray microcomputed tomography. Overall, the results demonstrated that the 3D-printed biocomposite bone scaffolds have promising potential for bone loss rehabilitation.

A computational analysis to evaluate deleterious SNPs of GSK3ß, a multifunctional and regulatory protein, for metabolism, wound healing, and migratory processes.

This study focused on GSK-3ß, a critical serine/threonine kinase with diverse cellular functions. However, there is limited understanding of the impact of non-synonymous single nucleotide polymorphisms (nsSNPs) on its structure and function. Through an exhaustive in-silico investigation 12 harmful nsSNPs were predicted from a pool of 172 acquired from the NCBI dbSNP database using 12 established tools that detects deleterious SNPs. Consistently, these nsSNPs were discovered in locations with high levels of conservation. Notably, the three harmful nsSNPs F67C, A83T, and T138I were situated in the active/binding site of GSK-3ß, which may affect the protein's capacity to bind to substrates and other proteins. Molecular dynamics simulations revealed that the F67C and T138I mutants had stable structures, indicating rigidness, whereas the A83T mutant was unstable. Analysis of secondary structures revealed different modifications in all mutant forms, which may affect the stability, functioning, and interactions of the protein. These mutations appear to alter the structural dynamics of GSK-3ß, which may have functional ramifications, such as the formation of novel secondary structures and variations in coil-to-helix transitions. In conclusion, this study illuminates the possible structural and functional ramifications of these GSK-3 nsSNPs, revealing how protein compactness, stiffness, and interactions may affect biological activities.

Enhanced bone regeneration usingAntheraea mylittasilk fibroin and chitosan based scaffold:in-vivoandin-vitrostudy.

In this study, highly interconnected porous scaffolds fromAntheraea mylittasilk fibroin (SF) and chitosan (CH) were fabricated using the freeze-drying method. The weight ratios of SF to CH were varied from 90:10 (SF90/CH10) to 50:50 (SF50/CH50) to prepare the scaffolds from the aqueous suspension of the protein-polysaccharide mix. From the initial optimization of scaffold composition with respect to their microstructure, porosity, and mechanical properties, the SF80/CH20scaffold exhibited the most suitable properties for bone tissue engineering application as compared to others compositions. Hencein-vitrohemocompatibility, protein adsorption, and MG-63 cell culture studies were carried out for SF80/CH20scaffold. The fabricated SF80/CH20scaffold showed a more controlled swelling percentage of 42.8%, with high BSA protein adsorption of 0.39 mg of BSA per gm of the scaffold at 24 h incubation period. Furthermore,in-vitroMG-63 cell culture study onto the fabricated SF80/CH20scaffold elicited excellent MG-63 cell attachment with better biocompatibility and cell viability with increased F-action production from day 3 to day 7 of the cell culture period.In vivobone defect healing in a rabbit tibia model revealed excellent bone healing capacity in SF80/CH20scaffold implanted specimens compared to control ones, as evident from histology and fluorochrome labeling analysis.

Controlled nano Cu precipitation through age treatment: A method to enhance the biodegradation, mechanical, antimicrobial properties and biocompatibility of Fe-20Mn-3Cu alloys.

Iron-manganese (Fe-Mn) based degradable biomaterials have been proven as a suitable substitute to permanent internal fracture-fixation devices. However, lower degradation and bacterial infection are still major concerns. To overcome these limitations, in this work, we have incorporated copper (Cu) in Fe-Mn system. The objective is to produce Cu nano-precipitates and refined microstructure through suitable combination of cold-rolling and age-treatment, so that degradation is improved eventually. High resolution transmission electron microscope (TEM) and scanning transmission electron microscope (STEM) confirmed the Cu rich composition of the nano-precipitates. Number of precipitates increased as aging time increased. Three-dimensional visualization of Fe, Mn and Cu atomic distributions using atom probe tomography (APT), indicated that Cu precipitates were in 15-50 nm range. Large number of nano-precipitates along with lower dislocation density led to highest strength (1078 MPa) and ductility (37 %) for the 6 h age-treated sample. On the other hand, nano-precipitates and refined microstructure resulted highest degradation for the 12 h of age treated sample (0.091 mmpy). When E.Coli bacteria was cultured with the sample extract, significantly higher antibacterial efficacy was observed for the sample having higher nano-precipitates. Higher degradation rate did not cause cyto-toxicity, rather promoted statistically higher cell proliferation (1.5 times within 24 h) in in vitro cell-material interaction studies. In vivo biocompatibility of the alloy containing large nano-precipitates was confirmed from higher new bone regeneration (60%) in rabbit femur model. Overall study suggested that the optimization of the thermo-mechanical processes can effectively tailor the Fe-Mn-Cu alloys for successful internal fracture fixation. STATEMENT OF SIGNIFICANCE: In the present work, we have reported a noble thermo-mechanical approach to simultaneously achieve Cu nano-precipitates and grain refinement in Fe-20Mn-3Cu alloy.

In Vitro and In Vivo Bone Regeneration Assessment of Titanium-Doped Waste Eggshell-Derived Hydroxyapatite in the Animal Model.

In this work, a titanium-doped hydroxyapatite (HAp) scaffold was produced from two different sources (natural eggshell and laboratory-grade reagents) to compare the efficacy of natural and synthetic resources of HAp materials on new bone regeneration. This comparative study also reports the effect of Ti doping on the physical, mechanical, and in vitro as well as in vivo biological properties of the HAp scaffold. Pellets were prepared in the conventional powder metallurgy route, compacted, and sintered at 900 °C, showing sufficient porosity for bony ingrowth. The physical-mechanical characterizations were performed by density, porosity evaluation, XRD, FTIR, SEM analysis, and hardness measurement. In vitro interactions were evaluated by bactericidal assay, hemolysis, MTT assay, and interaction with simulated body fluid. All categories of pellets showed absolute nonhemolytic and nontoxic character. Furthermore, significant apatite formation was observed on the Ti-doped HAp samples in the simulated body fluid immersion study. The developed porous pellets were implanted to assess the bone defect healing in the femoral condyle of healthy rabbits. A 2 month study after implantation showed no marked inflammatory reaction for any samples. Radiological analysis, histological analysis, SEM analysis, and oxytetracycline labeling studies depicted better invasion of mature osseous tissue in the pores of doped eggshell-derived HAp scaffolds as compared to the undoped HAp, and laboratory-made samples. Quantification using oxytetracycline labeling depicted 59.31 ± 1.89% new bone formation for Ti-doped eggshell HAp as compared to Ti-doped pure HAp (54.41 ± 1.93) and other undoped samples. Histological studies showed the presence of abundant osteoblastic and osteoclastic cells in Ti-doped eggshell HAp in contrast to other samples. Radiological and SEM data also showed similar results. The results indicated that Ti-doped biosourced HAp samples have good biocompatibility, new bone-forming ability, and could be used as a bone grafting material in orthopedic surgery.

Synergistic Effects of Cerium and Hot Forging on Biodegradation, Antibacterial Properties, and In Vivo Biocompatibility of Microalloyed Mg-Zr-Sr Alloys.

Biodegradable magnesium (Mg)-based alloys are potential candidates for orthopedic applications. In the present study, we have discussed the effect of cerium (Ce) addition and hot forging on mechanical properties, in vitro-in vivo corrosion, antibacterial activity, and cytocompatibility of microalloyed Mg-0.2Zr-0.1Sr-xCe (x = 0 [MZS], 0.5 wt % [MZS-Ce]) alloys. Addition of 0.5 wt % Ce to forged MZS alloys leads to strengthening of the basal texture as well as formation of a higher fraction of dynamic recrystallized (DRX) grains. Hot forging and addition of cerium to the MZS alloy improve both the yield strength and ultimate tensile strength of the forged MZS-Ce alloy by 1.39 and 1.21 times, respectively, compared to those of the forged MZS alloy. The potentiodynamic polarization test in Hank's solution indicates that the corrosion resistance of the forged MZS alloy improves with addition of 0.5 wt % Ce. Uniform distribution of Mg12Ce precipitates, a higher DRX fraction, strengthened texture, and formation of a compact CeO2 passive layer result in 1.68 times reduction in the immersion corrosion rate of the forged MZS-Ce alloy compared to that of the forged MZS alloy. Addition of Ce to the MZS alloy shows excellent antibacterial activity. The forged MZS-Ce alloy exhibited the highest antibacterial efficacy (76.73%). All the alloys show favorable cytocompatibility and alkaline phosphatase (ALP) activity with MC3T3-E1 cells. The improved corrosion resistance of the forged MZS-Ce alloy (95%) leads to higher cell viability compared to that of the forged MZS alloy (85%). In vivo biodegradation and the ability to generate new bones were analyzed by implanting cylindrical samples in the rabbit femur. Histological analysis showed no adverse effects around the implants. Gradual degradation of the implants and higher new bone formation around the forged MZS-Ce sample were confirmed by micro-CT analysis. Bone regeneration around the implants (58.21%) was validated by flurochrome labeling. After 60 days, the forged MZS-Ce alloy showed controlled corrosion and better bone-implant integration, presenting it as a potential candidate for internal fracture fixation materials.

Polymeric biomaterials-based tissue engineering for wound healing: a systemic review.

Background: Biomaterials are vital products used in clinical sectors as alternatives to several biological macromolecules for tissue engineering techniques owing to their numerous beneficial properties, including wound healing. The healing pattern generally depends upon the type of wounds, and restoration of the skin on damaged areas is greatly dependent on the depth and severity of the injury. The rate of wound healing relies on the type of biomaterials being incorporated for the fabrication of skin substitutes and their stability in in vivo conditions. In this review, a systematic literature search was performed on several databases to identify the most frequently used biomaterials for the development of successful wound healing agents against skin damage, along with their mechanisms of action. Method: The relevant research articles of the last 5 years were identified, analysed and reviewed in this paper. The meta-analysis was carried out using PRISMA and the search was conducted in major scientific databases. The research of the most recent 5 years, from 2017-2021 was taken into consideration. The collected research papers were inspected thoroughly for further analysis. Recent advances in the utilization of natural and synthetic biomaterials (alone/in combination) to speed up the regeneration rate of injured cells in skin wounds were summarised. Finally, 23 papers were critically reviewed and discussed. Results: In total, 2022 scholarly articles were retrieved from databases utilizing the aforementioned input methods. After eliminating duplicates and articles published before 2017, ~520 articles remained that were relevant to the topic at hand (biomaterials for wound healing) and could be evaluated for quality. Following different procedures, 23 publications were selected as best fitting for data extraction. Preferred Reporting Items for Systematic Reviews and Meta-Analyses for this review illustrates the selection criteria, such as exclusion and inclusion parameters. The 23 recent publications pointed to the use of both natural and synthetic polymers in wound healing applications. Information related to wound type and the mechanism of action has also been reviewed carefully. The selected publication showed that composites of natural and synthetic polymers were used extensively for both surgical and burn wounds. Extensive research revealed the effects of polymer-based biomaterials in wound healing and their recent advancement. Conclusions: The effects of biomaterials in wound healing are critically examined in this review. Different biomaterials have been tried to speed up the healing process, however, their success varies with the severity of the wound. However, some of the biomaterials raise questions when applied on a wide scale because of their scarcity, high transportation costs and processing challenges. Therefore, even if a biomaterial has good wound healing qualities, it may be technically unsuitable for use in actual medical scenarios. All of these restrictions have been examined closely in this review.

In vitro and in vivo assessment of decellularized platelet-rich fibrin-loaded strontium doped porous magnesium phosphate scaffolds in bone regeneration.

The present work reports the effect of decellularized platelet-rich fibrin (dPRF) loaded strontium (Sr) doped porous magnesium phosphate (MgP) bioceramics on biocompatibility, biodegradability, and bone regeneration. Sustained release of growth factors from dPRF is a major objective here, which conformed to the availability of dPRF on the scaffold surface even after 7 days of in vitro degradation. dPRF-incorporated MgP scaffolds were implanted in the rabbit femoral bone defect and bone rejuvenation was confirmed by radiological examination, histological examination, fluorochrome labeling study, and micro-CT. µ-CT examination of the regained bone samples exhibited that invasion of mature bone in the pores of the MgP2Sr-dPRF sample was higher than the MgP2Sr which indicated better bone maturation capability of this composition. Quantifiable assessment using oxytetracycline labeling showed 73.55 ± 1.12% new osseous tissue regeneration for MgP2Sr-dPRF samples in contrast to 65.47 ± 1.16% for pure MgP2Sr samples, after 3 months of implantation. Histological analysis depicted the presence of abundant osteoblastic and osteoclastic cells in dPRF-loaded Sr-doped MgP samples as compared to other samples. Radiological studies also mimicked similar results in the MgP2Sr-dPRF group with intact periosteal lining and significant bridging callus formation. The present results indicated that dPRF-loaded Sr-doped magnesium phosphate bioceramics have good biocompatibility, bone-forming ability, and suitable biodegradability in bone regeneration.

In vivo biocompatibility of SrO and MgO doped brushite cements.

The addition of dopants in biomaterials has emerged as a critical regulator of bone formation and regeneration due to their imminent role in the biological process. The present work evaluated the role of strontium (Sr) and magnesium (Mg) dopants in brushite cement (BrC) on in vivo bone healing performance in a rabbit model. Pure, 1 wt% SrO (Sr-BrC), 1 wt% MgO (Mg-BrC), and a binary composition of 1.0 wt% SrO + 1.0 wt% MgO (Sr + Mg-BrC) BrCs were implanted into critical-sized tibial defects in rabbits for up to 4 months. The in vivo bone healing of three doped and pure BrC samples was examined and compared using sequential radiological examination, histological evaluations, and fluorochrome labeling studies. The results indicated excellent osseous tissue formation for Sr-BrC and Sr + Mg-BrC and moderate bone regeneration for Mg-BrC compared to pure BrC. Our findings indicated that adding small amounts of SrO, MgO, and binary dopants to the BrC can significantly influence new bone formation for bone tissue engineering.

In Vitro Degradation and In Vivo Biocompatibility of Strontium-Doped Magnesium Phosphate-Reinforced Magnesium Composites.

Magnesium is projected for use as a degradable orthopedic biomaterial. However, its fast degradation in physiological media is considered as a significant challenge for its successful clinical applications. Bioactive reinforcements containing Mg-based composites constitute one of the promising approaches for developing degradable metallic implants because of their adjustable mechanical behaviors, corrosion resistance, and biological response. Strontium is a trace element known for its role in enhancing osteoblast activity. In this study, bioactive SrO-doped magnesium phosphate (MgP)-reinforced Mg composites containing 1, 3, and 5 wt % MgP were developed through the casting route. The influence of the SrO-doped MgP reinforcement on degradation behaviors of the composites along with its cell-material interactions and in vivo biocompatibility was investigated. The wt % and distribution of MgP particles significantly improved the mechanical properties of the composite. HBSS immersion study indicated the least corrosion rate (0.56 ± 0.038 mmpy) for the Mg-3MgP composite. The higher corrosion resistance of Mg-3MgP leads to a controlled release of Sr-containing bioactive reinforcement, which eventually enhanced the cytotoxicity as measured using MG-63 cell-material interactions. The in vivo biocompatibility of the composite was evaluated using the rabbit femur defect model. Micro-computed tomography (µ-CT) and histological analysis supported the fact that Mg-3MgP maintained its structural integrity and enhanced osteogenesis (50.36 ± 2.03%) after 2 months of implantation. The results indicated that the Mg-MgP composite could be used as a degradable internal fracture fixation device material.

Copper and cobalt doped bioactive glass-fish dermal collagen electrospun mat triggers key events of diabetic wound healing in full-thickness skin defect model.

The wounds arising out of underlying hyperglycemic conditions such as diabetic foot ulcers demand a multifunctional tissue regeneration approach owing to several deficiencies in the healing mechanisms. Herein, four different types of electrospun microfibers by combining Rohu fish skin-derived collagen (Fcol) with a bioactive glass (BAG)/ion-doped bioactive glass, namely, Fcol/BAG, Fcol/CuBAG, Fcol/CoBAG, and Fcol/CuCoBAG was developed to accelerate wound healing through stimulation of key events such as angiogenesis and ECM re-construction under diabetic conditions. SEM analysis shows the porous and microfibrous architecture, while the EDX mapping provides evidence of the incorporation of dopants inside various inorganic-organic composite mats. The viscoelastic properties of the microfibrous mats as measured by a nano-DMA test show a higher damping factor non-uniform tan-delta value. The maximum ultimate tensile strength and toughness are recorded for fish collagen with copper doped bioactive glass microfibers while the least values are demonstrated by microfibers with cobalt dopant. In vitro results demonstrate excellent cell-cell and cell-material interactions when human dermal fibroblasts (HDFs) were cultured over the microfibers for 48 h. When these mats were applied over full-thickness diabetic wounds in the rabbit model, early wound healing is attained with Fcol/CuBAG, Fcol/CoBAG, and Fcol/CuCoBAG microfibers. Notably, these microfibers-treated wounds demonstrate a significantly (p < 0.01) higher density of blood vessels by CD-31 immunostaining than control, Duoderm, and Fcol/BAG treated wounds. Mature collagen deposition and excellent ECM remodeling are also evident in wounds treated with fish collagen/ion-doped bioactive glass microfibers suggesting their positive role in diabetic wound healing.

Biomaterial-Based Therapeutic Approaches to Osteoarthritis and Cartilage Repair Through Macrophage Polarization.

There is an ever-increasing clinical and socioeconomic burden associated with cartilage lesions & osteoarthritis (OA). Its progression, chondrocyte death & hypertrophy are all facilitated by inflamed synovium & joint environment. Due to their capacity to switch between pro- & anti-inflammatory phenotypes, macrophages are increasingly being recognized as a key player in the healing process, which has been largely overlooked in the past. A biomaterial's inertness has traditionally been a goal while developing them in order to reduce the likelihood of adverse reactions from the host organism. A better knowledge of how macrophages respond to implanted materials has made it feasible to determine the biomaterial architectural parameters that control the host response & aid in effective tissue integration. Thus, this review summarizes novel therapeutic techniques for avoiding OA or increasing cartilage repair & regeneration that might be developed using new technologies tuning macrophages into desirable functional phenotypes.