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Designing scaffolds that can regulate the innate immune response and promote vascularized bone regeneration holds promise for bone tissue engineering. Herein, electrospun scaffolds that combined physical and biological cues were fabricated by anchoring reparative M2 macrophage–derived exosomes onto topological pore structured nanofibrous scaffolds. The topological pore structure of the fiber and the immobilization of exosomes increased the nanoscale roughness and hydrophilicity of the fibrous scaffold. In vitro cell experiments showed that exosomes could be internalized by target cells to promote cell migration, tube formation, osteogenic differentiation, and anti-inflammatory macrophage polarization. The activation of fibrosis, angiogenesis, and macrophage was elucidated during the exosome-functionalized fibrous scaffold–mediated foreign body response (FBR) in subcutaneous implantation in mice. The exosome-functionalized nanofibrous scaffolds also enhanced vascularized bone formation in a critical-sized rat cranial bone defect model. Importantly, histological analysis revealed that the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. This study elaborated on the complex processes within the cell microenvironment niche during fibrous scaffold–mediated FBR and vascularized bone regeneration to guide the design of implants or devices used in orthopedics and maxillofacial surgery. How to design scaffold materials that can regulate the local immune niche and truly achieve functional vascularized bone regeneration still remain an open question. Here, combining physical and biological cues, we proposed new insight to cell-free and growth factor-free therapy, anchoring reparative M2 macrophage–derived exosomes onto topological pore structured nanofibrous scaffolds. The exosomes functionalized-scaffold system mitigated foreign body response, including excessive fibrosis, tumor-like vascularization, and macrophage activation. Importantly, the biofunctional scaffolds regulated the coupling effect of angiogenesis, osteoclastogenesis, and osteogenesis by stimulating type H vessel formation. [Display omitted] [ABSTRACT FROM AUTHOR]

The fate of biomaterials is orchestrated by biocompatibility and bioregulation characteristics, reported to be closely related to topographical structures. For the purpose to investigate the topography of fibrous membranes on the guided bone regeneration performance, we successfully fabricated poly (lactate- co -glycolate)/fish collagen/nano-hydroxyapatite (PFCH) fibrous membranes with random, aligned and latticed topography by electrospinning. The physical, chemical and biological properties of the three topographical PFCH membranes were systematically investigated by in vitro and in vivo experiments. The subcutaneous implantation of C57BL6 mice showed an acceptable mild foreign body reaction of all three topological membranes. Interestingly, the latticed PFCH membrane exhibited superior abilities to recruit macrophage/monocyte and induce angiogenesis. We further investigated the osteogenesis of the three topographical PFCH membranes via the critical-size calvarial bone defect model of rats and mice and the results suggested that latticed PFCH membrane manifested promising performance to promote angiogenesis through upregulation of the HIF-1α signaling pathway; thereby enhancing bone regeneration. Our research illustrated that the topological structure of fibrous membranes, as one of the characteristics of biomaterials, could regulate its biological functions, and the fibrous structure of latticed topography could serve as a favorable surface design of biomaterials for bone regeneration. In material-mediated regeneration medicine, the interaction between the biomaterial and the host is key to successful tissue regeneration. The micro-and nano-structure becomes one of the most critical physical clues for designing biomaterials. In this study, we fabricated three topological electrospun membranes (Random, Aligned and Latticed) to understand how topological structural clues mediate bone tissue regeneration. Interestingly, we found that the Latticed topographical PFCH membrane promotes macrophage recruitment, angiogenesis, and osteogenesis in vivo , indicating the fibrous structure of latticed topography could serve as a favorable surface design of biomaterials for bone regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

A guided bone regeneration membrane is a pivotal therapeutic modality used to maintain sufficient space for bone regeneration, which is of great significance in curing alveolar bone defects. Metformin has been found to possess the ability of promoting osteogenic differentiation of bone mesenchymal stem cells. To develop guided bone regeneration membranes with better osteoinductive ability, metformin was incorporated into polycaprolactone/chitosan nanofibrous membranes by electrospinning technique, followed by glutaraldehyde crosslinking to reinforce chitosan stability in aqueous solutions. The fabricated nanofibrous membranes were then characterized by scanning electron microscope, Fourier transform infrared spectroscopy, water contact angle testing, mechanical properties test, and drug release test. Furthermore, rats bone mesenchymal stem cells were seeded on membranes for the evaluation of the effect of metformin-loaded polycaprolactone/chitosan nanofibrous membranes on cell morphology, alkaline phosphate activity, and osteogenic mineralization in vitro. Our results showed that nanofibers were fabricated successfully with smooth surface free from beads formation. The crosslinked-polycaprolactone/chitosan/metformin membranes had a more appropriate water contact angle of 44.25 ± 1.37° and the drug release curve of metformin featured early sudden release and slow release in the later stage over a 23-day period. Besides, in vitro studies suggested that the crosslinked-polycaprolactone/chitosan/metformin membrane was more suitable for cell adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells. Consequently, the metformin-loaded polycaprolactone/chitosan nanofibrous membranes would be promoted for bone regeneration as guided bone regeneration membranes. [ABSTRACT FROM AUTHOR]

Membranes play pivotal role in guided bone regeneration (GBR) technique for reconstruction alveolar bone. GBR membrane that is able to stimulate both osteogenic and angiogenic differentiation of cells may be more effective in clinic practice. Herein, we fabricated the Sr-doped calcium phosphate/polycaprolactone/chitosan (Sr-CaP/PCL/CS) nanohybrid fibrous membrane by incorporating 20 wt% bioactive Sr-CaP nanoparticles into PCL/CS matrix via one-step electrospinning method, in order to endow the membrane with stimulation of osteogenesis and angiogenesis. The physicochemical properties, mechanical properties, Sr2+ release behavior, and the membrane stimulate bone mesenchymal stem cell (BMSCs) differentiation were evaluated in comparison with PCL/CS and CaP/PCL/CS membranes. The SEM images revealed that the nanocomposite membrane mimicked the extracellular matrix structure. The release curve presented a 28-day long continuous release of Sr2+ and concentration which was certified in an optimal range for positive biological effects at each timepoint. The in vitro cell culture experiments certified that the Sr-CaP/PCL/CS membrane enjoyed excellent biocompatibility and remarkably promoted rat bone mesenchymal stem cell (BMSCs) adhesion and proliferation. In terms of osteogenic differentiation, BMSCs seeded on the Sr-CaP/PCL/CS membrane showed a higher ALP activity level and a better matrix mineralization. What's more, the synergism of the Sr2+ and CaP from the Sr-CaP/PCL/CS membrane enhanced BMSCs angiogenic differentiation, herein resulting in the largest VEGF secretion amount. Consequently, the Sr-CaP/PCL/CS nanohybrid electrospun membrane has promising applications in GBR. [ABSTRACT FROM AUTHOR]

Objective To study the microstructure of the Ag-nHA-nTiO2/PA66 membrane and investigate its bio-compatibility. Methods The microstructure of Ag-nHA-nTiO2/PA66 membrane and e-polytetra fluoroethylene (e-PTFE) membrane were observed by light microscope and scanning electron microscope (SEM). MG63 osteoblast-like cells were cultured on the two kinds of membrane and blank group. The cell proliferation was checked by methyl thiazolyl tetrazolium (MTT) method and alkaline phosphatase (ALP) activity was detected by enzyme linked immunosorbent assay (ELISA). The adhesion and proliferation of the cells on the two kinds of membrane was observed by SEM. Results The Ag-nHA-nTiO2/PA66 membrane was composed of the obverse face and the opposite face. The obverse face was porous and the opposite face was smooth. Microstructures of the obverse and the opposite face of the e-PTFE membrane were same. The e-PTFE membrane showed many tiny lined cracks in elliptic structure. MTT assay and ALP measurement showed that there were no significant difference between each of the two membrane groups and the blank (P>0.05). The adhesion and proliferation of cells on the Ag-nHA-nTiO2/PA66 membrane were better than the e-PTFE membrane. Conclusion Ag-nHA-nTiO2/PA66 membrane has no negative effects on the growth of osteoblast-like cells. Ag-nHA-nTiO2/PA66 membrane is biocompatible and its microstructure is appropriate as a guided bone regeneration materials. [ABSTRACT FROM AUTHOR]

In this study, the effects of a chitosan bioelectret membrane on bone regeneration in a rabbit cranial defect model were examined. The bioelectret was fabricated by film casting and polarized by grid-controlled corona charging (−1 kV). In vitro, the equivalence surface charge density of the bioelectret gradually reduced under both wet and dry conditions. In vivo, two rectangular transosseous defects of 8 mm × 10 mm were created symmetrically on each rabbit cranial bone. The defects were treated with the bioelectret membrane, with unpolarized membrane, and no membrane, respectively. The rabbits were killed at 4, 8, and 12 weeks postoperatively, and specimens were examined by micro-computed tomography and histological analysis. The bioelectret membrane recipients had a significantly higher volume of newly formed bone and greater rate of material degradation than the unpolarized membrane. Furthermore, the bioelectret membrane induced new bone formation not only around the host bone but also in the center of the defects. The chitosan bioelectret membrane application has an apparent potential in guided bone regeneration applications. [ABSTRACT FROM PUBLISHER]

A composite slurry from silver ion-substituted nano-hydroxyapatite, titania nano-particles and polyamide 66 (Ag-nHA/TiO2/PA66) was prepared and used to fabricate a novel antimicrobial membrane with a gradient porous structure for guided bone regeneration (GBR). Subsequently, assays were performed to determine the cytocompatibility, as well as the bone biocompatibility of the prepared membranes. To investigate the cytocompatibility of the Ag-nHA/TiO2/PA66 membrane, in vitro studies were done with osteoblast-like cells (MG63) and the viability, alkaline phosphatase activity (ALP) and morphology of cells cultured on the membrane were determined. The bone biocompatibility of the membranes was finally assessed in animal experiments, in which nano-hydroxyapatite/polyamide 66 (nHA/PA66) and pure polyamide 66 (PA66) membranes were compared. The in vitro cell-culture experiments showed that Ag-nHA/TiO2/PA66 antimicrobial membrane evoked good cell affinity and cytocompatibility. The in vivo study showed that Ag-nHA/TiO2/PA66 asymmetric porous barrier membrane resulted in complete closure of 5-mm bone defects as created in the skull of rats after 8 weeks of implantation. In conclusion, the Ag-nHA/TiO2/PA66 membrane has the potential to be applied in GBR, especially in infected tissue or areas with high bacteria concentration. [ABSTRACT FROM AUTHOR]

An electrospun polysulfone (PSU) was prepared as a barrier membrane for guided bone regeneration. The membrane was in nanoscale to prevent fibrous tissue infiltration and highly porous to allow permeation of oxygen and nutrients. The morphology and attachment, viability and proliferation, and differentiation and mineralization of human bone marrow mesenchymal stem cells (HBMSCs) were determined. Cells adhered and spread well on the PSU membrane with characteristic polygonal, fusiform shapes and radial extensions. The live/dead staining revealed that the membrane had no negative influence on cell viability. The proliferation rates of HBMSCs on PSU membranes were lower in comparison with tissue-culture polystyrene plate after 3 days of culture. However, differentiation activity was particularly expressed at high levels when cells were cultured on PSU membranes. The results based on the data suggest that the PSU electrospun membrane promoted the osteogenic differentiation of HBMSCs, displayed desirable in vitro biocompatibility, and has good potential as a barrier membrane. [ABSTRACT FROM AUTHOR]

A nano-hydroxyapatite/polyamide 66 (nHA/PA66) composite with good bioactivity and osteoconductivity is employed to develop a novel porous membrane with an asymmetric structure. In order to investigate the biocompatibility and the effect on guided bone regeneration (GBR) of nHA/PA66 porous membrane, the proliferation, viability, morphology and alkaline phosphatase activity (ALP) of the osteoblast-like cell line (MG63) cultured on the membrane were studied in vitro. In vivo biocompatibility and osteogenesis of the fabricated membrane were assessed by comparing guiding rats calvarial bone defects regeneration with "gold standard" GBR material, expanded polytetrafluoroethylene (e-PTFE) membrane. In vitro experiments showed that the nHA/PA66 composite membrane had good cell affinity and cytocompatibility, in favor of cell proliferation. The in vivo study showed that the nHA/PA66 asymmetric porous membrane had a good GBR effect. All the results indicate that the asymmetric porous nHA/PA66 composite GBR membrane with good biocompatibility, high bioactivity and osteoconductivity exhibits good GBR effect and has a potential to be applied in GBR fields, especially in dental tissue regeneration. [ABSTRACT FROM AUTHOR]

Objective: The biosafety and efficacy of silver–hydroxyapatite–titania/polyamide nanocomposite (nAg–HA–TiO2/PA) membrane as a guided bone regeneration (GBR) barrier were investigated based on a rat subcutaneous and critical-size calvarial defect model. Material and methods: Thirty-six Sprague–Dawley albino rats were divided into nAg–HA–TiO2/PA membrane test, expanded polytetrafluoroethylene (e-PTFE) membrane control and blank control. Inflammatory response and bone regeneration in each group were evaluated using morphological, serological, radiographic and histological techniques at 1, 4 and 8 weeks, respectively, after implantation. Results: For subcutaneous implantation, slight degradation of nAg–HA–TiO2/PA membranes was observed by scanning electron microscope at 4 and 8 weeks. Histopathologic examination demonstrated a thinner layer of granulation tissue in the vicinity of nAg–HA–TiO2/PA membranes than that of e-PTFE membranes. For cranial defect implantation, the serum alkaline phosphatase level was remarkably higher in nAg–HA–TiO2/PA group than that in e-PTFE group. Radiographic and histomorphometric analysis showed a fully closed cranial defect for both nAg–HA–TiO2/PA and e-PTFE groups at 8 weeks. No remarkable difference was found between the two groups regarding the integral optical density of neo-bone at each time interval. Conclusion: nAg–HA–TiO2/PA membranes demonstrated better biocompatibility and similar osteoinductive activity compared with e-PTFE membranes. nAg–HA–TiO2/PA composite membranes provided a good prospect for further research and development in anti-bacterial GBR membrane. To cite this article: Zhang JC, Xu Q, Huang C, Mo AC, Li JD, Zuo Y. Biological properties of an anti-bacterial membrane for guided bone regeneration: an experimental study in rats. Clin. Oral Impl. Res. 21, 2010; 321–327. doi: 10.1111/j.1600-0501.2009.01838.x [ABSTRACT FROM AUTHOR]