Guided Bone Tissue Regeneration Research Articles

Development of electrospun electroactive polyurethane membranes for bone repairing.

To fabricate electroactive fibrous membranes and provide simulated bioelectric micro-environment for bone regeneration mimicking nature periosteum, a series of electroactive polyurethanes (PUAT) were synthesized using amino-capped aniline trimers (AT) and lysine derivatives as chain extenders. These PUAT were fabricated into fibrous membranes as guided bone tissue regeneration membranes (GBRMs) via electrospinning. The ultraviolet-visible (UV-vis) absorption spectroscopy and cyclic voltammetry (CV) of PUAT copolymers showed that the electroactive PUAT fibrous membranes had good electroactivity. Besides, the introduction of AT significantly improved the hydrophobicity and thermal stability of PUAT fibrous membranes and decreased the degradation rate of PUAT fibers in vitro. With the increasing content of AT incorporated into copolymers, the tensile strength and Young's modulus of PUAT fibrous membranes increased from 4MPa (PUAT0) to 15MPa (PUAT10) and from 2.1MPa (PUAT0) to 18MPa (PUAT10), respectively. The cell morphology and proliferation of rat mesenchymal stem cells (rMSCs) on PUAT fibers indicated that the incorporation of AT enhanced the cell attachment and proliferation. Moreover, the expression levels of OCN, CD31, and VEGF secreted by rMSCs on PUAT fibers increased with the increasing content of AT. In conclusion, an electroactive polyurethane fibrous membrane mimicking natural periosteum was prepared via electrospinning and showed good potential application in guiding bone tissue regeneration.

Advances in autogenous dentin matrix graft as a promising biomaterial for guided bone regeneration in maxillofacial region: A review.

Autogenous dentin matrix (ADM), derived from a patient's extracted tooth, can be repurposed as an autologous grafting material in reconstructive dentistry. Extracted teeth provide a source for ADM, which distinguishes itself with its low rejection rate, osteoinductive capabilities and ease of preparation. Consequently, it presents a viable alternative to autogenous bone. Animal studies have substantiated its effective osteoinductive properties, while its clinical applications encompass post-extraction site preservation, maxillary sinus floor augmentation, and guided bone tissue regeneration. Nevertheless, the long-term efficacy of ADM applied in bone regeneration remains underexplored and there is a lack of standardization in the preparation processes. This paper comprehensively explores the composition, mechanisms underlying osteoinductivity, preparation methods, and clinical applications of ADM with the aim of establishing a fundamental reference for future studies on this subject.

Effects of MgO nanoparticle addition on the mechanical properties, degradation properties, antibacterial properties and in vitro and in vivo biological properties of 3D-printed Zn scaffolds

Bone tissue engineering is the main method for repairing large segment bone defects. In this study, a layer of bioactive MgO nanoparticles was wrapped on the surface of spherical Zn powders, which allowed the MgO nanoparticles to be incorporated into 3D-printed Zn matrix and improved the biodegradation and biocompatibility of the Zn matrix. The results showed that porous pure Zn scaffolds and Zn/MgO scaffolds with skeletal-gyroid (G) model structure were successfully prepared by selective laser melting (SLM). The average porosity of two porous scaffolds was 59.3 and 60.0%, respectively. The pores were uniformly distributed with an average pore size of 558.6–569.3 μm. MgO nanoparticles regulated the corrosion rate of scaffolds, resulting in a more uniform corrosion degradation behavior of the Zn/MgO scaffolds in simulated body fluid solution. The degradation ratio of Zn/MgO composite scaffolds in vivo was increased compared to pure Zn scaffolds, reaching 15.6% at 12 weeks. The yield strength (10.8 ± 2.4 MPa) of the Zn/MgO composite scaffold was comparable to that of cancellous bone, and the antimicrobial rate were higher than 99%. The Zn/MgO composite scaffolds could better guide bone tissue regeneration in rat cranial bone repair experiments (completely filling the scaffolds at 12 weeks). Therefore, porous Zn/MgO scaffolds with G-model structure prepared with SLM are a promising biodegradable bone tissue engineering scaffold.

Combinatorial anticancer effects of multi metal ion and drug substitute with hydroxyapatite coatings on surgical grade 316LSS stainless steel alloys towards biomedical applications

The present study highlights the metal ions and existing drug ampicillin-loaded nano-hydroxyapatite (nHAP) coated on 316 stainless steel alloy (316LSS) using the electrodeposition method. In addition, the sample phase purity and crystallinity of the HAp composite coatings on 316LSS were analyzed by X-ray diffraction analysis (XRD) and Fourier transform infrared (FT-IR) spectroscopy using the KBr pellet method. The coating microstructure/morphology was characterized using a scanning electron microscope, which showed a flower-like morphology with the attachment of energy-dispersive X-ray spectroscopy (EDX) to confirm the major element groups in the synthesized sample. The TGA results showed that weight loss occurred in the temperature range of up to 800 °C for oxidation and reduction reactions. Additionally, the beat-optimized nanomaterial showed promising in vitro bioactivity against disease-causing microorganisms, displaying a significant zone of inhibition. Furthermore, cytotoxicity assessment using the MTT assay demonstrated that the synthesized samples effectively inhibited cell proliferation in human osteosarcoma cell lines (Saos-2). AO/EB double staining performed under a fluorescence microscope indicated changes in the morphology of the apoptotic cell nuclei. In addition, the relationship between ROS and nanomaterial-induced apoptosis in Saos-2 cells was analyzed by flow cytometry. MMP (ΔѰmt) profiling showed that the HAp composite increased the effective mitochondrial membrane damage or depolarization in the human osteosarcoma cell line. Moreover, the TUNEL assay suggested that treated nanomaterial with Saos-2 cells showed enhanced green fluorescence intensity, indicating terminal DNA damage. The obtained results meet the recommended physiological standard for synthesized 316LSS HAp composites to guide bone tissue regeneration.

A composite membrane with microtopographical morphology to regulate cellular behavior for improved tissue regeneration.

Tissue engineering scaffolds with specific surface topographical morphologies can regulate cellular behaviors and promote tissue repair. In this study, poly lactic(co-glycolic acid) (PLGA)/wool keratin composite guided tissue regeneration (GTR) membranes with three types of microtopographies (three groups each of pits, grooves and columns, thus nine groups in total) were prepared. Then, the effects of the nine groups of membranes on cell adhesion, proliferation and osteogenic differentiation were examined. The nine different membranes had clear, regular and uniform surface topographical morphologies. The 2 µm pit-structured membrane had the best effect on promoting the proliferation of bone marrow mesenchymal stem cells(BMSCs) and periodontal ligament stem cells (PDLSCs), while the 10 µm groove-structured membrane was the best for inducing osteogenic differentiation of BMSCs and PDLSCs. Then, we investigated the ectopic osteogenic, guided bone tissue regeneration and guided periodontal tissue regeneration effects of the 10 µm groove-structured membrane combined with cells or cell sheets. The 10 µm groove-structured membrane/cell complex had good compatibility and certain ectopic osteogenic effects, and the 10 µm groove-structured membrane/cell sheet complex promoted better bone repair and regeneration and periodontal tissue regeneration. Thus, the 10 µm groove-structured membrane shows potential to treat bone defects and periodontal disease. STATEMENT OF SIGNIFICANCE: PLGA/wool keratin composite GTR membranes with microcolumn, micropit and microgroove topographical morphologies were prepared by dry etching technology and the solvent casting method. The composite GTR membranes had different effects on cell behavior. The 2 µm pit-structured membrane had the best effect on promoting the proliferation of rabbit BMSCs and PDLSCs and the 10 µm groove-structured membrane was the best for inducing the osteogenic differentiation of BMSCs and PDLSCs. The combined application ofa 10 µm groove-structured membrane and PDLSC sheet can promote better bone repair and regeneration as well as periodontal tissue regeneration. Our findings may have significant potential for guiding the design of future GTR membranes with topographical morphologies and clinical applications of the groove-structured membrane/cell sheet complex.

Effect of different preparation conditions on the properties of nano-hydroxyapatite/bamboo fiber composite membrane

Nano-hydroxyapatite/bamboo fiber (n-HA/BF) composite membranes were obtained by a simple casting technology. The mechanism of the membrane formation and the effects of different pre-drying conditions, drying methods and n-HA addition amounts on the properties of the n-HA/BF composite membranes were investigated by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM), contact angle, Electromechanical universal tester, in vitro soaking in simulated body fluid (SBF) and in vitro cell culture experiment. The results demonstrated that different preparation conditions did not affect the dispersity of n-HA nanoparticles in BF matrix, but determined the membrane appearances, owing to the different changes of hydrogen bond under different pre-drying temperatures. Moreover, the hydrophilicity of the composite membranes could be improved when the membranes were prepared at 70 °C and freeze-drying as well as n-HA high addition content, and the mechanical properties of the composite membranes depended on n-HA addition content. In vitro soaking behavior indicated that the corrosion properties and bone-like apatite deposition could be controlled by different preparation conditions. The cell proliferation results showed that the n-HA/BF composite membranes obtained in different preparation conditions were all non-toxic. The obtained results showed that the casting technique could be used to prepare n-HA/BF composite membranes, and the properties of the composite membranes could be controlled by adopting different preparation conditions, which would have a great potential for guide bone tissue regeneration (GBR) membranes, and the study would provide a new way for BF application in biomedical fields.Graphical abstractIn this manuscript, nano-hydroxyapatite/BF (n-HA/BF) composite membranes were prepared by casting method, and the membrane forming mechanism and the effects of different pre-drying conditions, drying methods and n-HA amounts on the corresponding n-HA/BF membrane were investigated. Results demonstrated that the morphologies of membrane was determined by the different preparation conditions owing to different hydrogen bond changes. Moreover, the hydrophilicity, the mechanical properties, the degradability and bone-like apatite deposition could be controlled by different preparation conditions, and all the n-HA/BF composite membranes were all non-toxic. The obtained results indicated that the n-HA/BF composite membrane with 20% n-HA prepared at room temperature has a great potential as guide bone tissue regeneration (GBR) membrane, which would provide a new application for BF in biomedical field.

The Osteogenic Role of Barium Titanate/Polylactic Acid Piezoelectric Composite Membranes as Guiding Membranes for Bone Tissue Regeneration.

PurposeBiopiezoelectric materials have good biocompatibility and excellent piezoelectric properties, and they can generate local currents in vivo to restore the physiological electrical microenvironment of the defect and promote bone regeneration. Previous studies of guided bone regeneration membranes have rarely addressed the point of restoring it, so this study prepared a Barium titanate/Polylactic acid (BT/PLA) piezoelectric composite membrane and investigated its bone-formation, with a view to providing an experimental basis for clinical studies of guided bone tissue regeneration membranes.MethodsBT/PLA composite membranes with different BT ratio were prepared by solution casting method, and piezoelectric properties were performed after corona polarization treatment. The optimal BT ratio was selected and then subjected to in vitro cytological experiments and in vivo osteogenic studies in rats. The effects on adhesion, proliferation and osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1) were investigated. The effect of composite membranes on bone repair of cranial defects in rats was investigated after 4 and 12 weeks.ResultsThe highest piezoelectric coefficient d33 were obtained when the BT content was 20%, reaching (7.03 ± 0.26) pC/N. The value could still be maintained at (4.47±0.17) pC/N after 12 weeks, meeting the piezoelectric constant range of bone. In vitro, the MC3T3-E1 cells showed better adhesion and proliferative activity in the group of polarized 20%BT. The highest alkaline phosphatase (ALP) content was observed in cells of this group. In vivo, it promoted rapid bone regeneration. At 4 weeks postoperatively, new bone formation was evident at the edges of the defect, with extensive marrow cavity formation; after 12 weeks, the defect was essentially completely closed, with density approximating normal bone tissue and significant mineralization.ConclusionThe BT/PLA piezoelectric composite membrane has good osteogenic properties and provides a new idea for guiding the research of membrane materials for bone tissue regeneration.

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects.

Reconstruction of critical-sized bone defects remains a tremendous challenge for surgeons worldwide. Despite the variety of surgical techniques, current clinical strategies for bone defect repair demonstrate significant limitations and drawbacks, including donor-site morbidity, poor anatomical match, insufficient bone volume, bone graft resorption, and rejection. Bone tissue engineering (BTE) has emerged as a novel approach to guided bone tissue regeneration. BTE focuses on in vitro manipulations with seed cells, growth factors and bioactive scaffolds using bioreactors. The successful clinical translation of BTE requires overcoming a number of significant challenges. Currently, insufficient vascularization is the critical limitation for viability of the bone tissue-engineered construct. Furthermore, efficacy and safety of the scaffolds cell-seeding and exogenous growth factors administration are still controversial. The in vivo bioreactor principle (IVB) is an exceptionally promising concept for the in vivo bone tissue regeneration in a predictable patient-specific manner. This concept is based on the self-regenerative capacity of the human body, and combines flap prefabrication and axial vascularization strategies. Multiple experimental studies on in vivo BTE strategies presented in this review demonstrate the efficacy of this approach. Routine clinical application of the in vivo bioreactor principle is the future direction of BTE; however, it requires further investigation for overcoming some significant limitations.

Metal-phenolic networks acted as a novel bio-filler of a barrier membrane to improve guided bone regeneration via manipulating osteoimmunomodulation.

A guided bone tissue regeneration membrane (GBRM) is traditionally viewed as an inert physical barrier to isolate soft tissue from the bone defect area. However, as a "foreign body", the implantation of a GBRM would inevitably modulate immune response and subsequently affect bone dynamics. Herein, we developed strontium ion (Sr2+)-based metal-phenolic network complexes (MPNs) as a novel type of bio-filler to manipulate the osteoimmunomodulation of the advanced GBRM. For controllable delivery of Sr2+ depending on the difference in affinity between phenolic ligands and Sr2+, tannic acid (TA), epigallocatechin gallate (EGCG), and epigallocatechin (EGC) were selected to chelate with Sr2+. The formed MPNs were incorporated into PCL nanofibrous membranes by blending electrospinning. Among them, TA/Sr based MPN particles displayed the most sustainable release profile of phenolic ligands and Sr2+. Further investigations demonstrated that Sr2+ could not only directly promote osteogenic differentiation of BMSCs, but also manipulate an anti-inflammatory osteoimmune microenvironment in a synergistic manner with TA, thus enhancing osteogenesis and inhibiting bone resorption. The rat alveolar bone defect model also confirmed that the TA/Sr nanoparticle modified membrane displayed better bone regeneration performance than the pure PCL membrane via inhibiting bone resorption. This work provides a new platform for controllable delivery of bioactive nutrient elements, and holds great promise for advancing multi-functional biocomposites.

Preparation and characterization of a novel composite membrane of natural silk fiber/nano-hydroxyapatite/chitosan for guided bone tissue regeneration

Abstract Natural silk fiber (SF) was introduced into the chitosan/nano-hydroxyapatite (CS/n-HA) system to fabricate a novel guided bone tissue regeneration (GBR) membrane. The effect of different treatment methods (degummed, un-degummed, or dissolved SF) and different contents of SF on the properties of the CS/n-HA composite membrane was investigated. Results demonstrated that the degummed SF/CS/n-HA composite membrane with a weight ratio of 2:6:2 possessed the highest mechanical strength, where SF supported the composite membrane as a skeleton frame in the form of primeval state, while the un-degummed SF and dissolved SF had weaker reinforce effect due to the poor interface or poor interaction between SF and CS, and the dissolved SF/CS/n-HA composite membrane displayed the fastest degradation. However, the three SF could all improve the cell biocompatibility of the CS/n-HA composite membrane. Conclusively, the study revealed that degummed SF could in situ reinforce the CS/n-HA composite membrane with a simple and green processing method, which would provide an important guidance significant to develop a novel GBR membrane.

Metal-phenolic networks as a novel filler to advance multi-functional immunomodulatory biocomposites

Here, we exploited the potential applications of metal-phenolic networks (MPNs) as a novel type of filler for next-generation multi-functional immunomodulatory biocomposites. Tannic acid (TA) and Mg2+ were selected as the model phenolic ligand and metal ion, respectively, and used to assemble MPN particles, and a TA-Mg/polycaprolactone (PCL) composite nanofibrous scaffold was then prepared by blending electrospinning. Measurements of the resultant composite scaffold verified strong hydrogen-bonding interactions between TA motifs and PCL chains and the good dispersity of MPN particles throughout the substrate. Due to the pH-responsive disassembly kinetics of MPN complexes, both TA and Mg2+ displayed pH-responsive sustained release behaviour, thus eliciting significant biological effects. Specifically, TA and Mg2+ synergistically generated an anti-inflammatory micro-environment, which was beneficial for osteogenesis, and Mg2+ directly stimulated the osteogenic differentiation of stem cells. Consequently, the composite membrane significantly enhanced in vivo osteogenic performance when used as a barrier membrane to guide bone tissue regeneration. One unique advantage of this filler is that it combines the functions of both metal ions and phenolic ligands. By selecting different phenolic ligands and metal ions, a series of novel MPN-based fillers with unique functions could be easily obtained, suggesting that this system has a wide range of potential applications for next-generation multi-functional biocomposites.

Control Release of Adenosine Potentiate Osteogenic Differentiation within a Bone Integrative EGCG-g-NOCC/Collagen Composite Scaffold toward Guided Bone Regeneration in a Critical-Sized Calvarial Defect.

The regeneration of critical-sized bone defects with biomimetic scaffolds remains clinically challenging due to avascular necrosis, chronic inflammation, and altered osteogenic activity. Two confounding mechanisms, efficacy manipulation, and temporal regulation dictate the scaffold's bone regenerative ability. Equally critical is the priming of the mesenchymal stromal cells (MSCs) toward lineage-specific differentiation into bone-forming osteoblast, which particularly depends on varied mechanochemical and biological cues during bone tissue regeneration. This study sought to design and develop an optimized osteogenic scaffold, adenosine/epigallocatechin gallate-N,O-carboxymethyl chitosan/collagen type I (AD/EGCG-g-NOCC@clgn I), having osteoinductive components toward swift bone regeneration in a calvarial defect BALB/c mice model. The ex vivo findings distinctly establish the pro-osteogenic potential of adenosine and EGCG, stimulating MSCs toward osteoblast differentiation with significantly increased expression of alkaline phosphatase, calcium deposits, and enhanced osteocalcin expression. Moreover, the 3D matrix recapitulates extracellular matrix (ECM) properties, provides a favorable microenvironment, structural support against mechanical stress, and acts as a reservoir for sustained release of osteoinductive molecules for cell differentiation, proliferation, and migration during matrix osteointegration observed. Evidence from in vivo experiments, micro-CT analyses, histology, and histomorphometry signify accelerated osteogenesis both qualitatively and quantitatively: effectual bone union with enhanced bone formation and new ossified tissue in 4 mm sized defects. Our results suggest that the optimized scaffold serves as an adjuvant to guide bone tissue regeneration in critical-sized calvarial defects with promising therapeutic efficacy.

Guided bone tissue regeneration using a hollow calcium phosphate based implant in a critical size rabbit radius defect

Long bone fractures are common and sometimes difficult to treat. Autologous bone (AB), bovine bone and calcium phosphates are used to stimulate bone growth with varying results. In the present study, a calcium phosphate cement (CPC) that previously showed promising grafting capabilities was evaluated for the first time in a long bone defect. A radius defect of 20 mm was created in 20 rabbits. The defect was filled by either a hollow CPC implant that had been manufactured as a replica of a rabbit radius through indirect 3D printing, or by particulate AB as control. Defect filling and bone formation was evaluated after 12 weeks by combining micro computed tomography (μCT) and scoring of 3D images, together with histomorphometry and histology. The μCT and histomorphometric evaluations showed a similar amount of filling of the defect (combining graft and bone) between the CPC and AB group, but the scoring of 3D images showed that the filling in the CPC group was significantly larger. Histologically the AB graft could not be distinguished from the new bone. The AB treated defects were found to be composed of more bone than the CPC group, including reorganised cancellous and cortical bone. Both the CPC and AB material was associated with new bone formation, also in the middle of the defect, which could result in closing of the otherwise critically sized gap. This study shows the potential for an indirectly 3D printed implant in guided bone regeneration in critically sized long bone defects.

Study on proanthocyanidins crosslinked collagen membrane for guided bone tissue regeneration.

The goal of this study is to understand the ability of a newly developed barrier membrane to enhance bone tissue regeneration. Here in this study we present the in vitro characterization of the barrier membrane made from type I collagen and crosslinked by oligomeric proanthocyanidins (OPCs). The effects of the membrane (P-C film) on cell cycle, proliferation, alkaline phosphatase activity, and mineralization were evaluated using the human osteoblast cell line MG-63, while the barrier ability was examined using MG-63 cells, as well as the human skin fibroblast cell line WS-1. The pore size is one of the factors that plays a key role in tissue regeneration, therefore, we evaluated the pore size of the membrane using a capillary flow porometer. Our results showed that the mean pore size of the P-C film was approximately 7-9 µm, the size known to inhibit cell migration across the membrane. The P-C film also demonstrated excellent cell viability and good biocompatibility, since the cell number increased with time, with MG-63 cells proliferating faster on the P-C film than in the cell culture flask. Furthermore, the P-C film promoted osteoblast differentiation, resulting in higher alkaline phosphatase activity and mineralization. Therefore, our results suggest that this P-C film has a great potential to be used in guided bone regeneration during periodontal regeneration and bone tissue engineering.

Carboxymethyl chitosan/sodium alginate-based micron-fibers fabricated by emulsion electrospinning for periosteal tissue engineering

Periosteum provides nourishment to bones and facilitates osteogenesis. The structural and functional impairment of periosteum can cause bone regeneration difficulties. Artificial periosteum with suitable mechanical properties and chemical composition can effectively guide bone tissue regeneration. In this study, a polycaprolactone (PCL)/carboxymethyl chitosan (CMCS)/sodium alginate (SA) micron-fibrous bionic periosteum was prepared. The water-in-oil PCL-CMCS/SA emulsion was prepared by using Span 80 as the emulsifier, and the PCL/CMCS/SA composite micron-fibers were fabricated by emulsion electrospinning. The physicochemical properties of the PCL/CMCS/SA micron-fibers were investigated via SEM, FTIR and tensile test analyses. CCK8 assay, live/dead assay, cell adhesion, and qPCR tests were carried out to evaluate the osteoinductive capacity of the micron-fibers and their biocompatibility to MC3T3-E1 osteoblasts. The results showed that CMCS and SA were successfully immobilized in the micron-fibers. The PCL/CMCS/SA micron-fibers showed an average diameter of 2.381 ± 1.068 μm with excellent tensile strength. The PCL/CMCS/SA composite scaffold demonstrated no significant cytotoxicity and could facilitate osteoblast adhesion. In addition, it could upregulate the early expression of osteogenic genes ALP and Runx2. The PCL/CMCS/SA micron-fibers prepared by emulsion electrospinning showed good mechanical properties, excellent biocompatibility and osteoinductive capacity to osteoblasts, and could be used as potential transplantable scaffolds for repairing large-segment bone defects.

Hierarchically multi-functionalized graded membrane with enhanced bone regeneration and self-defensive antibacterial characteristics for guided bone regeneration

Functional graded nanofibrous membrane (FGM) are gaining great attention in biomedical fields for the reason that it allows tunning the composition, structure, and bioactivity of each layer. Herein, we reported a novel FGM prepared by sequential electrospinning technique to guide bone tissue regeneration. The FGM consisted of two aligned gelatin nanofiber surface layers to improve the biocompatibility and enhance bone regeneration, and a random PCL nanofiber core layer to render the membrane isotropic mechanical strength. To eliminate bacterial infection risk, the pro-metronidazole (Pro-MNA) with infection-responsive release property was synthesized and loaded into the outer layer. The FGM displayed comparable mechanical strength with PCL, and similar biocompatibility to gelatin. The surface aligned nanofiber structure could regulate epithelial cell spread along the aligned direction, instead of infiltration growth, and were more beneficial for the migration and proliferation of osteoblast. In addition, the loaded Pro-MNA displayed infection-responsive release behavior, and robust self-defensive antibacterial function was achieved. These results suggested that the FGM simultaneously fulfil several criteria of biocompatibility, space maintaining capability, antibacterial property, and osteoconductivity. Consequently, the FGM displayed better bone regeneration performance than the commercial Bio-Gide membrane, evaluated by the skull defect model of rabbit. We concluded that the FGM had potential to be used as an ideal GTRM due to its improved overall performance.

Bioinspired Mineral–Organic Bone Adhesives for Stable Fracture Fixation and Accelerated Bone Regeneration

AbstractThe use of hydrogel‐based bone adhesives has the potential to revolutionize the clinical treatment of bone repairs. However, severe deficiencies remain in current products, including cytotoxicity concerns, inappropriate mechanical strength, and poor fixation performance in wet biological environments. Inspired by the unique roles of glue molecules in the robust mechanical strength and fracture resistance of bone, a design strategy is proposed using novel mineral–organic bone adhesives for strong water‐resistant fixation and guided bone tissue regeneration. The system leveraged tannic acid (TA) as a phenolic glue molecule to spontaneously co‐assemble with silk fibroin (SF) and hydroxyapatite (HA) in order to fabricate the inorganic–organic hybrid hydrogel (named SF@TA@HA). The combination of the strong affinity between SF and TA along with sacrificial coordination bonds between TA and HA significantly improves the toughness and adhesion strength of the hydrogel by increasing the amount of energy dissipation at the nanoscale. This in turn facilitated adequate and stable fixation of bone fracture in wet biological environments. Furthermore, SF@TA@HA promotes the regeneration of bone defects at an early stage in vivo. This work presents a type of bioinspired bone adhesive that is able to provide stable fracture fixation and accelerated bone regeneration during the bone remodeling process.

Особенности направленной регенерации костной ткани при использовании резорбируемых мембран на основе поливинилового спирта с добавлением фуллеренов C60

Особенности направленной регенерации костной ткани при использовании резорбируемых мембран на основе поливинилового спирта с добавлением фуллеренов C60

Effect of component and surface structure on poly(l-lactide-co-ɛ- caprolactone) (PLCA)-based composite membrane

To obtain an ideal guided bone tissue regeneration (GBR) membrane, a novel double-layered composite membrane was developed by combining the technology of solvent casting and electrospinning, which was composed of poly (l-lactide-co-ɛ-caprolactone) (PLCA) cast layer and Mg-substituted nano-hydroxyapatite (Mg-n-HA)/PLCA composite electrospun layer. The effect of different Mg-n-HA contents of 10 wt%, 20 wt%, 30 wt% and 40 wt% and membrane surface porous structure on mechanical properties, in vitro apatite deposit, cell biocompatibility and in vivo tissue regeneration of the composite membrane were investigated, using electronic universal testing machine, scanning electron microscope (SEM), in vitro simulated body fluids (SBF) soaking, cell culture experiment and in vivo skulls repair experiment of rabbits. The results showed that the addition of Mg-n-HA did not bring about negative effect on the mechanical properties, porous structure consisting of nanofibers and the degradation rate of the composite membrane. Instead, the high Mg-n-HA content and membrane surface porous structure greatly promoted the apatite deposit. Moreover, the Mg-n-HA/PLCA composite double-layered membranes displayed better cell proliferation and tissue biocompatibility, suggesting it had a great potential to be used as GBR membrane.

Synergistic effect of stem cells from human exfoliated deciduous teeth and rhBMP-2 delivered by injectable nanofibrous microspheres with different surface modifications on vascularized bone regeneration

To provide a suitable 3D microenvironment for bone regeneration, we selected the injectable poly (l-lactic acid) nanofibrous microspheres (PLLA NF-Ms) with different surface modifications to serve as cell micro-carriers or protein vehicles on-demand. Results showed that polydopamine (PDA) modified NF-Ms (PDA-NF-Ms) exhibited good affinity for stem cells from human exfoliated deciduous teeth (SHED), and Heparin-Dopamine (Hep-Dopa) conjugated with NF-Ms (Hep-Dopa NF-Ms) are able to immobilize and slowly release recombinant human bone morphogenic protein-2 (rhBMP-2) efficiently. In vivo evaluations were carried out in both ectopic subcutaneous implantation and orthotopic cranial bone defect nude mouse models (φ = 4 mm). The results suggested that PDA-NF-Ms could support SHED survival over 4 weeks. All experimental groups with SHED/PDA-NF-Ms engraftment showed angiogenesis activity. But, no effect of SHED/PDA-NF-Ms on osteogenesis was found in ectopic implantation, which is different from the result in cranial defect. The rhBMP-2 released from Hep-Dopa NF-Ms could significantly guide bone tissue regeneration in both ectopic and orthotopic site. At 8 weeks, both BMP-2 group and dual group showed large amounts of bone formation in situ, despite the fact that quantitative results of micro-CT did not demonstrate significant difference between them. More blood vessels were observed in SHED and Dual groups, which verifies the quality improvement of regenerated osseous tissues. Regeneration of vascularized bone tissue was, thus, highly expected upon implanting SHED/PDA-NF-Ms and rhBMP-2-loaded Hep-Dopa NF-Ms together. The strategy developed in this study represents a promising method for satisfactorily promoting bone regeneration.