Bone Regeneration Potential Research Articles

Biofunctionalization of electrospun fiber membranes by LbL-collagen/chondroitin sulfate nanocoating followed by mineralization for bone regeneration

It is of great significance to develop osteoinductive artificial scaffold for bone repair and regeneration. We constructed a biomimetic apatite interface on electrospun polycaprolactone fibers by combining layer-by-layer (LbL) nanocoating with mineralization to fabricate an osteoinductive artificial scaffold. After polydopamine modification, cationic type-І collagen and anionic chondroitin sulfate were sequentially adsorbed on the fiber surface. The fibers coated with the multilayer components served as the precursor matrix to induce apatite deposition. By adjusting the number of the layers and duration of mineralization, the nanoscale morphology of composite fibers was optimized. When ten bilayers of the collagen and chondroitin sulfate were deposited onto the fibers followed by one day-mineralization, the obtained polycaprolactone–apatite composite scaffolds significantly promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. In a subcutaneous implantation in mice, this composite fiber membrane enhanced in vivo ectopic osteogenesis. Our nano-architectural scaffolds were able to mimic the composition and structure of the bone matrix to a certain extent, holding great potential for bone repair and regeneration.

Treatment with a long-acting chimeric CSF1 molecule enhances fracture healing of healthy and osteoporotic bones

Macrophage-targeted therapies, including macrophage colony-stimulating factor 1 (CSF1), have been shown to have pro-repair impacts post-fracture. Preclinical/clinical applications of CSF1 have been expedited by development of chimeric CSF1-Fc which has extended circulating half-life. Here, we used mouse models to investigate the bone regenerative potential of CSF1-Fc in healthy and osteoporotic fracture. We also explored whether combination of CSF1-Fc with interleukin (IL)-4 provided additional fracture healing benefit in osteopenic bone. Micro-computed tomography, in situ histomorphometry, and bone mechanical parameters were used to assess systemic impacts of CSF1-Fc therapy in naive mice (male and female young, adult and geriatric). An intermittent CSF1-Fc regimen was optimized to mitigate undesirable impacts on bone resorption and hepatosplenomegaly, irrespective of age or gender. The intermittent CSF1-Fc regimen was tested in a mid-diaphyseal femoral fracture model in healthy bones with treatment initiated 1-day post-fracture. Weekly CSF1-Fc did not impact osteoclasts but increased osteal macrophages and improved fracture strength. Importantly, this treatment regimen also improved fracture union and strength in an ovariectomy-model of delayed fracture repair. Combining CSF1-Fc with IL-4 initiated 1-week post-fracture reduced the efficacy of CSF1-Fc. This study describes a novel strategy to specifically achieve bone regenerative actions of CSF1-Fc that has the potential to alleviate fragility fracture morbidity and mortality.

Chitin-hydroxyapatite-collagen composite scaffolds for bone regeneration

Bone defect is usually difficult to recover quickly, and bone scaffold transplantation is considered to be an effective method. Biomaterials have a wide range of application prospects in bone tissue repair, and the two key problems are the selection of materials and cells. The object of this study was to discuss the structural characteristics of bone scaffold materials and their effects on bone repair in vivo. The chitin-hydroxyapatite (HAP)-collagen composite scaffolds (CHCS) was prepared with epichlorohydrin (ECH) as crosslinking agent. The structure was characterized and the compressive strength, porosity, water absorbency and stability were investigated. The biocompatibility and osteogenic differentiation of CHCS in vitro were detected, and the effect of defect repair in vivo was evaluated. The results suggested that HAP not only enhanced the compressive strength of CHCS, but also promoted the formation of calcium nodules due to its bone conductivity. Histological staining showed that collagen promoted collagen deposition and new bone formation. X-ray images also indicated that CHCS transplantation accelerated bone repair. Therefore, CHCs has immense potential in bone regeneration.

Thermo-responsive chitosan/silk fibroin/amino-functionalized mesoporous silica hydrogels with strong and elastic characteristics for bone tissue engineering

Amino-functionalized mesoporous silica nanoparticles with radially porous architecture were optimally synthesized, and they were used together with silk fibroin and chitosan to produce a type of covalently crosslinked composite hydrogel using genipin as a crosslinker. The optimally achieved composite gels were found to be thermo-responsive at physiological temperature and pH with well-defined injectability. They were also detected to have mechanically strong and elastic characteristics. In addition, these gels showed the ability to release bioactive Si ions suited to an effective dose range in approximately linear manners for a few weeks. Studies on the cell-gel constructs revealed that the composite gels well supported the growth of seeded MC3T3-E1 cells, and the deposition of matrix components. Results obtained from the detection of alkaline phosphatase activity and the matrix mineralization in the cell-gel constructs confirmed that these composite gels had certain osteogenic capacity. The obtained results suggest that these composite gels have promising potential in bone repair and regeneration.

High toughness resorbable brushite-gypsum fiber-reinforced cements

The ideal bone substitute material should be mechanically strong, biocompatible with a resorption rate matching the rate of new bone formation. Brushite (dicalcium phosphate dihydrate) cement is a promising bone substitute material but with limited resorbability and mechanical properties. To improve the resorbability and mechanical performance of brushite cements, we incorporated gypsum (calcium sulfate dihydrate) and diazonium-treated polyglactin fibers which are well-known for their biocompatibility and bioresorbability. Here we show that by combining brushite and gypsum, we were able to fabricate biocompatible composite cements with high fracture toughness (0.47 MPa·m1/2) and a resorption rate that matched the rate of new bone formation. Adding functionalized polyglactin fibers to this composite cement further improved the fracture toughness up to 1.00 MPa·m1/2. XPS and SEM revealed that the improvement in fracture toughness is due to the strong interfacial bonding between the functionalized fibers and the cement matrix.This study shows that adding gypsum and functionalized polyglactin fibers to brushite cements results in composite biomaterials that combine high fracture toughness, resorbability, and biocompatibility, and have great potential for bone regeneration.

Addition of lactoferrin and substance P in a chitin/PLGA-CaSO4 hydrogel for regeneration of calvarial bone defects

Calcium-based injectable hydrogels with various bioactive active molecules possess a great potential for bone regeneration. Herein, we have synthesized a chitin-PLGA-calcium sulfate hydrogel (CSG) containing bioactive molecules - lactoferrin (LF) and substance P (SP). SEM and XRD analysis revealed that CS crystal growth was altered with the addition of LF. Rheological measurements indicated that the injectability of the hydrogels was maintained after the addition of LF, however, there was a reduction in storage modulus after LF addition. The addition of LF increased stem cell proliferation whereas, SP enhanced the cell migration. Osteogenic gene expression revealed that LF concentration at 25 μg/mg of CSG was optimal for a favourable outcome. To this optimized LF containing CSG, SP was incorporated and 0.05 μg/mg was found to be most effective (CSG-L3S2) in vitro studies. Further, the μ-CT and histological studies confirmed that CSG-L3S2 showed enhanced bone regeneration compared to the controls in critical-sized calvarial defect of mice. Thus the results indicate that a combination of the chemotactic agent (SP), pleiotropic growth protein (LF), and CS in the chitin-PLGA hydrogel could be a promising approach for non-load bearing bone defects.

Cathelicidin LL37 Promotes Osteogenic Differentiation in vitro and Bone Regeneration in vivo.

Different types of biomaterials have been used to repair the defect of bony orbit. However, exposure and infections are still critical risks in clinical application. Biomaterials with characteristics of osteogenesis and antibiosis are needed for bone regeneration. In this study, we aimed to characterize the antimicrobial effects of cathelicidin-LL37 and to assess any impacts on osteogenic activity. Furthermore, we attempted to demonstrate the feasibility of LL37 as a potential strategy in the reconstruction of clinical bone defects. Human adipose-derived mesenchyme stem cells (hADSCs) were cultured with different concentrations of LL37 and the optimum concentration for osteogenesis was selected for further in vitro studies. We then evaluated the antibiotic properties of LL37 at the optimum osteogenic concentration. Finally, we estimated the efficiency of a PSeD/hADSCs/LL37 combined scaffold on reconstructing bone defects in the rat calvarial defect model. The osteogenic ability on hADSCs in vitro was shown to be dependent on the concentration of LL37 and reached a peak at 4 μg/ml. The optimum concentration of LL37 showed good antimicrobial properties against Escherichia coli and Staphylococcus anurans. The combination scaffold of PSeD/hADSCs/LL37 showed superior osteogenic properties compared to the PSeD/hADSCs, PSeD, and control groups scaffolds, indicating a strong bone reconstruction effect in the rat calvarial bone defect model. In Conclusion, LL37 was shown to promote osteogenic differentiation in vitro as well as antibacterial properties. The combination of PSeD/hADSCs/LL37 was advantageous in the rat calvarial defect reconstruction model, showing high potential in clinical bone regeneration.

Bone Regeneration Using PEVAV/β-Tricalcium Phosphate Composite Scaffolds in Standardized Calvarial Defects: Micro-Computed Tomographic Experiment in Rats.

Bone regeneration using beta-tricalcium phosphate (β-TCP) can be practiced using a biocomposite scaffold. Poly(ethylene-co-vinylalcohol)/poly(δ-valerolactone)/β-tricalcium phosphate (PEVAV/β-TCP) composite scaffolds showed promising in vitro results. This study evaluated the bone regenerative potential of PEVAV/β-TCP biocomposite scaffolds in standardized calvarial defects in a rat model over 4 and 10 weeks. Bilateral calvarial defects (5 mm in diameter and about 1.5 mm thick, equivalent to the thickness of the calvaria) were created in 40 male Wistar albino rats. The defects were grafted with either commercially available β-TCP (positive control), PEVAV/β-TCP 70, or PEVAV/β-TCP 50, or left empty (negative control), depending on the group to which the animal was randomly assigned, to be covered before flap closure with resorbable collagen membrane (RCM). At 4 and 10 weeks post-surgery, the collected rat calvaria were evaluated using micro computed tomography (micro-CT) analysis, to assess the newly formed bone volume (NFBV), newly formed bone mineral density (NFBMD), and remaining graft volume (RGV). The results showed that calvarial defects grafted with the PEVAV/β-TCP biocomposite exhibited higher NFBV than did control defects, both at 4 and 10 weeks post-surgery. Furthermore, calvarial defects grafted with PEVAV/β-TCP 70 showed the highest NFBV among all grafting conditions, with a statistically significant difference recorded at 10 weeks post-surgery. The PEVAV/β-TCP composite scaffold showed potentiality for the regeneration of critical-sized calvarial bone defects in a rat model.

Comparison of Bone regeneration in hADMSC Versus hUCBMSC with hBMMSC as a Reference: A Literature Review of Potential Bone Regeneration

Mesenchymal stem cells (MSCs) are an important class of stem cells that can differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs must express CD105, CD73, and CD90 and differentiate into osteoblasts, adipocytes, and chondroblasts. The beneficial effects of MSCs on bone remodeling are mainly provided by a paracrine effect. In bone regeneration, implanted hADMSCs secrete various osteoblast-activating factors, receptor activator of nuclear factor kappa-B ligand (RANKL), BMP-2, BMP-4, hepatocyte growth factor (HGF) and bone-related extracellular matrix proteins. The MSCs possess multipotent capabilities, paracrine, autocrine, and migration capacity to the tissue, directly initiating healing and regeneration with a specified standard. hADMSCs has demonstrated bone regenerative capabilities. DLX5 and RUNX2 as potential bone regeneration references by looking at the osteogenic cells of each source cell. The ability of hADMSC bone regeneration is higher than hUCBMSC due to the capacity of hADMSC osteogenesis which leads to bone and cartilage formation.

Gelatin-biofermentative unsulfated glycosaminoglycans semi-interpenetrating hydrogels via microbial-transglutaminase crosslinking enhance osteogenic potential of dental pulp stem cells.

Gelatin hydrogels by microbial-transglutaminase crosslinking are being increasingly exploited for tissue engineering, and proved high potential in bone regeneration. This study aimed to evaluate, for the first time, the combination of enzymatically crosslinked gelatin with hyaluronan and the newly developed biotechnological chondroitin in enhancing osteogenic potential. Gelatin enzymatic crosslinking was carried out in the presence of hyaluronan or of a hyaluronan–chondroitin mixture, obtaining semi-interpenetrating gels. The latter proved lower swelling extent and improved stiffness compared to the gelatin matrix alone, whilst maintaining high stability. The heteropolysaccharides were retained for 30 days in the hydrogels, thus influencing cell response over this period. To evaluate the effect of hydrogel composition on bone regeneration, materials were seeded with human dental pulp stem cells and osteogenic differentiation was assessed. The expression of osteocalcin (OC) and osteopontin (OPN), both at gene and protein level, was evaluated at 7, 15 and 30 days of culture. Scanning electron microscopy (SEM) and two-photon microscope observations were performed to assess bone-like extracellular matrix (ECM) deposition and to observe the cell penetration depth. In the presence of the heteropolysaccharides, OC and OPN expression was upregulated and a higher degree of calcified matrix formation was observed. Combination with hyaluronan and chondroitin improved both the biophysical properties and the biological response of enzymatically crosslinked gelatin, fastening bone deposition.

Spatio-temporal characterization of fracture healing patterns and assessment of biomaterials by time-lapsed in vivo micro-computed tomography

Thorough preclinical evaluation of functionalized biomaterials for treatment of large bone defects is essential prior to clinical application. Using in vivo micro-computed tomography (micro-CT) and mouse femoral defect models with different defect sizes, we were able to detect spatio-temporal healing patterns indicative of physiological and impaired healing in three defect sub-volumes and the adjacent cortex. The time-lapsed in vivo micro-CT-based approach was then applied to evaluate the bone regeneration potential of functionalized biomaterials using collagen and bone morphogenetic protein (BMP-2). Both collagen and BMP-2 treatment led to distinct changes in bone turnover in the different healing phases. Despite increased periosteal bone formation, 87.5% of the defects treated with collagen scaffolds resulted in non-unions. Additional BMP-2 application significantly accelerated the healing process and increased the union rate to 100%. This study further shows potential of time-lapsed in vivo micro-CT for capturing spatio-temporal deviations preceding non-union formation and how this can be prevented by application of functionalized biomaterials. This study therefore supports the application of longitudinal in vivo micro-CT for discrimination of normal and disturbed healing patterns and for the spatio-temporal characterization of the bone regeneration capacity of functionalized biomaterials.

Polymer-Protein Hybrid Network Involving Mucin: A Mineralized Biomimetic Template for Bone Tissue Engineering.

Biomimetic matrices offer a great advantage to understand several biological processes including regeneration. The study involves the development of a hybrid biomimetic scaffold and the uniqueness lies in the use of mucin, as a constituent protein. Through this study, the role of the protein in bone regeneration is deciphered through its development as a 3D model. As a first step towards understanding the protein, the interactions of mucin and collagen are determined by in silico studies considering that collagen is the most abundant protein in the bone microenvironment. Both proteins are reported to be involved in bone biology though the exact role of mucin is a topic of investigation. The in silico studies of collagen-mucin suggest to have a proper affinity toward each other, forming a strong basis for 3D scaffold development. The developed 3D scaffold is a double network system comprising of mucin and collagen and vinyl end functionalized polyethylene glycol. In situ deposition of mineral crystals has been performed enzymatically. Biological evaluation of these mineral deposited scaffolds is done in terms of their bone regeneration potential and a comparison of the two systems with and without mineral deposition is presented.

Bovine-Derived Xenografts Immobilized With Cryopreserved Stem Cells From Human Adipose and Dental Pulp Tissues Promote Bone Regeneration: A Radiographic and Histological Study.

Adipose tissue-derived stem cells (ADSCs) and dental pulp stem cells (DPSCs) have become promising sources for bone tissue engineering. Our study aimed at evaluating bone regeneration potential of cryopreserved ADSCs and DPSCs combined with bovine-derived xenografts with 10% porcine collagen. In vitro studies revealed that although DPSCs had higher proliferative abilities, ADSCs exhibited greater mineral depositions and higher osteogenic-related gene expression, indicating better osteogenic differentiation potential of ADSCs. After applying cryopreserved ADSCs and DPSCs in a critical-sized calvarial defect model, both cryopreserved mesenchymal stem cells significantly improved bone volume density and new bone area at 2, 4, and 8 weeks. Furthermore, the combined treatment with ADSCs and xenografts was more efficient in enhancing bone repair processes compared to combined treatment with DPCSs at all-time points. We also evaluated the sequential early bone healing process both histologically and radiographically, confirming a high agreement between these two methods. Based on these results, we propose grafting of the tissue-engineered construct seeded with cryopreserved ADSCs as a useful strategy in accelerating bone healing processes.

Photobiomodulation combined with adipose-derived stem cells encapsulated in methacrylated gelatin hydrogels enhances in vivo bone regeneration.

Reconstruction of bone defects is still a significant challenge. The aim of this study was to evaluate the effect of application of photobiomodulation (PBM) to enhance in vivo bone regeneration and osteogenic differentiation potential of adipose-derived stem cells (ADSCs) encapsulated in methacrylated gelatin (GEL-MA) hydrogels. Thirty-six Sprague-Dawley rats were randomly separated into 3 experimental groups (n = 12 each). The groups were control/blank defect (I), GEL-MA hydrogel (II), and ADSC-loaded GEL-MA (GEL-MA+ADSC) hydrogel (III). Biparietal critical sized bone defects (6 mm in size) are created in each animal. Half of the animals from each group (n = 6 each) were randomly selected for PBM application using polychromatic light in the near infrared region, 600-1200 nm. PBM was administered from 10 cm distance cranially in 48 h interval. The calvaria were harvested at the 20th week, and macroscopic, microtomographic, and histologic evaluation were performed for further analysis. Microtomographic evaluation demonstrated the highest result for mineralized matrix formation (MMF) in group III. PBM receiving samples of group III showed mean MMF of 79.93±3.41%, whereas the non-PBM receiving samples revealed mean MMF of 60.62±6.34 % (p=0.002). In terms of histologic evaluation of bone defect repair, the higher scores were obtained in the groups II and III when compared to the control group (2.0 for both PBM receiving and non-receiving specimens; p<0.001). ADSC-loaded microwave-induced GEL-MA hydrogels and periodic application of photobiomodulation with polychromatic light appear to have beneficial effect on bone regeneration and can stimulate ADSCs for osteogenic differentiation.

Bone morphogenetic protein 2: heterologous expression and potential in bone regeneration

Currently, bone morphogenetic protein 2 (BMP-2) is one of the two osteoinductive growth factors used in medical devices to promote bone formation. Typically, this protein is bought from commercial houses at high rates and in small quantities that are not enough to cover clinical needs. Because of this, it has been proposed that research centers use their own heterologous expression systems to have a constant supply of BMP-2. The aim of this study was to standardize the heterologous expression of BMP-2 and evaluate its osteoinductive activity in vitro. Our procedure for expression and purification was based on recombinant DNA technology using the plasmid pET-28 and IPTG as inductor. After extracting the protein from inclusion bodies, folding it and modifying it via a redox system, we observed via electrophoresis a 26 kDa dimer. We evaluated its osteoinductive activity in myoblastic C2C12 by quantifying enzymatically the activity of alkaline phosphate (ALP) and staining mineralization nodules. ALP activity is proportional to BMP-2 concentration, increasing 90% at 3 µg/mL. These cells form calcium nodules, mineralizing 50% of the area.

Human Periodontal Ligament Stem Cells Transplanted with Nanohydroxyapatite/Chitosan/Gelatin 3D Porous Scaffolds Promote Jaw Bone Regeneration in Swine.

Dental-tissue-derived stem cells have been used for tissue engineering owing to their ease of isolation and efficacy in in vitro and in vivo proliferation and differentiation. Nanohydroxyapatite/chitosan/gelatin (nHA/CG) three-dimensional porous scaffolds are promising for bone tissue engineering, especially jaw bone regeneration, because of their structural and functional similarity to natural bone. In our previous study, the efficiency of scaffolds with stem cell complexes in osteogenesis was confirmed in vivo in immunocompromised mice. However, studies on the bone regeneration efficiency of stem cell-seeded nHA/CG scaffolds using large animal jaw bone defect models have not been conducted. This study evaluated the bone regeneration potential of the nHA/CG scaffolds with transplanted human periodontal ligament stem cells (hPDLSCs) in critical-sized jaw bone defects in minipigs. The hPDLSCs isolated from periodontal ligaments of discarded teeth (postorthodontic purposes) were seeded onto the nHA/CG scaffolds. The scaffold was successfully synthesized according to our previous studies. Forty-eight critical-sized jaw bone defects were created in 12 minipigs. The defects were randomly assigned to one of three groups [scaffolds with seeded hPDLSCs (hPDLSCs/nHA/CG), only scaffold (nHA/CG), and a negative control group, ie, no cells and scaffolds implanted into defects] to investigate jaw bone regeneration. The bone regeneration capacities of the three groups were assessed for up to 12 weeks. The results showed that the hPDLSCs adhered well to the nHA/CG scaffold in vitro, and the cell-nHA/CG composites significantly increased new bone formation and generated large bones with normal architectures and vascularization in vivo compared to the nHA/CG and control groups. Immunohistochemistry staining showed that runt-related transcription factor 2 (Runx2) was highly expressed in the bone marrow formed in the hPDLSCs/nHA/CG group. This study provides strong evidence for future clinical applications of the nHA/CG scaffolds transplanted with hPDLSCs to regenerate the bone in large jaw bone defects.

Effectiveness of Chitosan Nanohydrogel as a Bone Regenerative Material in Intrabony Defects in Patients With Chronic Periodontitis: A Randomized Clinical Trial

Aim: Different procedures have been attempted to regenerate intrabony defects in periodontitis but complete regeneration is still a herculean feat. Nanoparticles could prove to be advantageous because of their small size and increased surface area. The aim was to evaluate the effectiveness of a chitosan nanohydrogel as a periodontal regenerative material in the management of intrabony defects. Materials and Methods: Twenty patients within the age group of 30 to 60 years with intrabony defects &gt;3 mm and clinical attachment levels &gt;5 mm were selected. They were divided randomly into two groups: group-1, which received only open flap debridement with bone graft and acted as control, and group-2, which received open flap debridement, bone graft mixed with a chitosan nanohydrogel, and acted as the test site. Clinical and radiographic measurements were recorded at baseline, three months, and six months. Intragroup comparison was done using a paired t-test and intergroup comparison was done using an unpaired t-test with the statistical value set at P &lt; .05. Results: Chitosan hydrogel incorporated bone grafts showed improved bone regenerative potential. The mean reduction in clinical attachment level in group-2 (8.7 ± 0.6 to 1.6 ± 0.8) was significantly higher than that of group-1 (8.6 ± 0.5 to 2.4 ± 0.7). The mean reduction in probing depths in group-2 (test group) was significantly higher (8.3 ± 0.9 to 1.6 ± 0.8) when compared to group-1 (8 ± 0.8 to 2.3 ± 0.7). Significant amount of defect fill was obtained in both the groups from baseline to six-month period. Conclusion: Organic materials such as chitosan could have potential bone regenerative capacity.

Development of a decellularized porcine bone graft by supercritical carbon dioxide extraction technology for bone regeneration.

A series of novel decellularized porcine collagen bone graft (DPB) materials in a variety of shapes and sizes were developed by the supercritical carbon dioxide (SCCO2 ) extraction technique. The complete decellularization of DPB was confirmed by hematoxylin and eosin staining, 4,6-diamidino-2-phenylindole (DAPI) staining, and residual DNA analysis. The native intact collagen remained in the DPB after the SCCO2 process was confirmed by Masson trichrome staining. The physicochemical characteristics of DPB were investigated by scanning electron microscopy and x-ray diffraction. The cytotoxicity and biocompatibility tests according to ISO10993 and its efficacy for bone regeneration in osteochondral defects in rabbits were evaluated. The rabbit pyrogen test confirmed DPB was non-toxic. In vitro and in vivo biocompatibility tests of the DPB did not show any toxic or mutagenic effects. The bone regeneration potential of the DPB presented no significant histological differences compared to commercially available deproteinized bovine bone. In conclusion, DPB produced by SCCO2 exhibited similar chemical characteristics to human bone, no toxicity, good biocompatibility, and enhanced bone regeneration in rabbits comparable to that of deproteinized bovine bone. Results from this study could shed light on the potential application of the SCCO2 extraction technique to generate a native decellularized scaffold for bone tissue regeneration in human clinical trials.

Visual and antibacterial magnesium implants with low biocorrosion and bioactive surface for in vivo tracking and treating MRSA infection

• A multifunctional bioactive visual Mg-based implant (Mg@PCS) was fabricated facilely. • Mg@PCS possesses biodegradation/photoluminescence/osteogenic activity/antiinfection. • Mg@PCS implants could be tracked by fluorescence and treating MRSA infection in vivo . Magnesium (Mg) have a promising potential in orthopedic implantations and bone regeneration due to their biodegradation and resemblance modulus to native bone. However, the rapid corrosion/bacterial infection/single function probably limits their application. Herein, we utilized a facile surface self-assembly method to construct a multifunctional elastomeric bioactive poly(citrate-silicon) (PCS) coating on Mg through the ion bonding interaction (–COO-Mg) to obtain the Mg@PCS implants. Compared to the conventional Mg, Mg@PCS implants possess representative multifunctional properties including high corrosion resistance, low degradation and stable pH environment, controlled photoluminescence, robust antibacterial activity, enhanced cytocompatibility and osteogenic differentiation ability. The in vivo results suggested that Mg@PCS showed fluorescence-tracking ability, and could efficiently reduce the inflammatory response and treat the infection of methicillin-resistant Staphylococcus aureus ( MRSA ). This work probably provides a reasonable strategy to develop visual bioactive implants with antiinfection for regenerative medicine.

DOPA-derived electroactive copolymer and IGF-1 immobilized poly(lactic-co-glycolic acid)/hydroxyapatite biodegradable microspheres for synergistic bone repair

Abstract Owing to defect features (irregular shape and size) and local environments (e.g., pulsation of dura matter and proximity of the brain), the skull is one of the most difficult to repair. Electroactive microsphere systems with good injectability, adjustable size, high surface-to-volume ratio and surface modifiability, exhibit excellent bone regeneration potential. Herein, the electroactive microspheres were prepared by immobilizing aniline tetramer (AT) on poly(lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) microspheres. Subsequently, the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 (DOPA-IGF-1) inspired by bioorthogonal chemistry was designed by combining the recombinant DNA technology and tyrosinase treatment, and modified on electroactive scaffolds surface. The as-prepared microspheres exhibited excellent sphericity and homogeneity with an average diameter of 329.2 ± 16.5 μm. Interestingly, the electroactive microsphere exhibits significant cell proliferation and enhanced osteogenic differentiation, and combining with DOPA-IGF-1 can further synergistically induce mineralization and osteogenic differentiation. Rat calvarial defect repair experiments showed excellent repairability in forming mineralized collagen deposition within the transplanted composite microspheres scaffold in the bone defect site. Thus, biomimetic composite microsphere with electroactivity and bioactivity exhibits considerable potential for calvarial defect repair.