Guided Bone Regeneration Material Research Articles

Bredigite bioceramic-based barrier membrane promotes guided bone regeneration by orchestrating an immuno-modulatory and osteogenic microenvironment

Barrier membranes play an important role in guided bone regeneration (GBR) and have been primarily considered as physical barriers. Due to their inherent “foreign body” properties, barrier membranes introduced during GBR procedures unavoidably modify the local immune microenvironment, with consequent impacts on osteogenesis. In bone tissue engineering applications, inorganic bioceramics have been shown to possess the abilities to modulate the local immune response and promote the differentiation of stem cells along osteogenic lineages. Moreover, these bioceramics can be easily incorporated into scaffold membranes, thus demonstrating significant potential as a barrier membrane material for GBR. Herein, an inorganic bredigite (BRT, Ca7MgSi4O16) bioceramic-containing scaffold was fabricated and characterized, and its effects on the immune response and osteogenesis during GBR were investigated. The results indicated that the BRT-containing scaffolds promoted the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs). Single-cell RNA sequencing analysis indicated a unique microenvironment and subpopulation of BMSCs cultured on the BRT scaffolds, which exhibited increased osteo/chondrogenic and angiogenic differentiation potential. Furthermore, the BRT-containing scaffolds induced macrophage polarization into the pro-regenerative M2 phenotype, which subsequently promoted the migration and osteogenic differentiation of BMSCs. Additionally, in an in vivo rat model, the BRT-containing membrane was confirmed to enhance the immune microenvironment and support bone regeneration in a cranial critical-size defect. Collectively, these findings indicate that the BRT-containing scaffold membrane possesses dual immunomodulatory and osteogenic properties, offering a potentially beneficial GBR membrane for clinical application.

Silk fibroin hydrogel membranes prepared by a sequential cross-linking strategy for guided bone regeneration

Silk fibroin hydrogel is a widely used material for tissue engineering. However, its mechanical properties are the main obstacle to its application to medical bone regeneration barrier membranes. Here, we developed a new hydrogel membrane for guided bone regeneration (GBR). In this study, a sequential crosslinking strategy including photo crosslinking and organic solvent (ethanol) treatment was used to obtain silk fibroin hydrogel membrane (EA-SF). The mechanical properties of EA-SF were significantly enhanced compared to the hydrogel prepared only by photocrosslinking (E-SF). The compressive and tensile strengths of the hydrogel film treated with 75% ethanol for 6 h were 1.18 ± 0.36 MPa and 0.43 ± 0.03 MPa, respectively. In vitro cell culture results showed that EA-SF has good biocompatibility and can effectively shield fibroblasts (L929). EA-SF also has excellent in vitro protein hydrolysis stability. In vivo experiments (subcutaneous implantation and calvarial defect experiment) confirmed the stability and barrier functionality of EA-SF. In conclusion, this study demonstrated that ethanol could improve the mechanical properties of silk fibroin hydrogel and extend the scope of their application, making silk fibroin hydrogel a promising GBR material.

Comprehensive reparative effects of bacteriostatic poly(L-lactide-co-glycolide)/poly(L-lactide-co-ε-caprolactone) electrospinning membrane on alveolar bone defects in progressive periodontitis.

Periodontitis is a chronic inflammatory disease that leads to the loss of alveolar bone, among several studies focusing on reconstructing periodontal bone caused by periodontitis, guided bone regeneration (GBR) is a promising approach. In this study a serial clinically applied antibiotics loaded poly(L-lactide-co-glycolide)/poly(L-lactide-co-ε-caprolactone) (PLGA/PLCA) fibrous mesh to prevent and reconstruct defective bone in periodontitis were prepared by electrospinning. Incorporation of antibiotics promoted the hydrophilicity but decreased the crystallinity of PLGA/PLCA membranes. Antibiotics could be sustained released from membranes. Metronidazole, minocycline, and doxycycline incorporated membranes could suppress Porphyromonas gingivalis (P. gingivalis) within 21 days in vitro. Metronidazole and minocycline incorporated membranes decreased 41% and 55.5% colony counts in rat gingival crevicular fluid in vivo. Minocycline-loaded membrane could support the proliferation of MC3T3-E1 cells and maintained 79% viability of human ligament fibroblasts cultured on it. And MC3T3-E1 cells could undergo osteoblastic differentiation when cultured with pure PLGA/PLCA membrane and minocycline incorporated membrane. Then in vivo repairable effects of those antibiotics loaded membranes were evaluated in alveolar bone defected P. gingivalis infected model. The application of minocycline loaded membranes, effectively prevented the bone resorption of periodontitis caused by P. gingivalis. After been treated with minocycline incorporated membrane, volume of defected bone of maintained at about 50% level of control rats. 8 weeks post-operation, newly regenerated bone was observed in the operative alveolar bone of the pure PLGA/PLCA membrane, metronidazole and minocycline incorporated PLGA/PLCA membrane treated groups. Minocycline/PLGA/PLCA electrospinning membrane is a promising GBR material that can be applied to guide regeneration of periodontitis-induced alveolar bone damage.

State-of-the-art guided bone regeneration material

State-of-the-art guided bone regeneration material

Bioactive Glass Flakes as Innovative Fillers in Chitosan Membranes for Guided Bone Regeneration

Herein, novel bioactive glass flakes (BGFs) (45S5 composition), obtained by compression in the liquid phase in a stirred media mill, are combined with chitosan (CS) to develop composite membranes using solvent casting for guided bone regeneration (GBR). The incorporation of BGFs endows CS membranes with superior bioactivity as evidenced by rapid hydroxyapatite formation after 3 days of immersion in simulated body fluid (SBF). Moreover, the addition of BGFs reduces the swelling ratio of CS membranes, beneficial for GBR applications. The swelling behavior can also be modulated by tuning the added amount of BGFs. In vitro cell studies indicate the noncytotoxicity of composite membranes toward osteoblast cell line MC3T3‐E1, although the presence of BGFs slightly reduces the cell viability compared to pure CS membranes. The incorporation of BGFs also improves the osteogenic differentiation of MC3T3‐E1 cells as indicated by the enhanced alkaline phosphatase activity. The results show the feasibility of BGFs as anisotropic bioactive fillers in polymeric matrices. In conclusion, the developed CS‐BGF composite membranes show promising potential as a novel material for GBR.

Silicon-substituted hydroxyapatite reinforced 3D printed gelatin membrane for guided bone regeneration

Guided bone regeneration (GBR) warrants a bioactive membrane with biocompatibility, host tissue integration, and clinical moldability along with adequate mechanical and physical properties. Hydroxyapatite (HA) incorporated membranes have shown to promote the functional and osteogenic activity of stromal cells towards GBR. Also, many studies have demonstrated that the addition of trace elements such as Silicon-substituted HA (SiHA) accelerates and enhances bioactivity compared to HA. In this study, HA and SiHA were incorporated with gelatin (Gel) which is a biocompatible, low-cost, and cell-attractant, and widely used material for GBR. The three-dimensional printed construct provides for topography with interconnected pores that permit selective cell occlusion; a desirable property for GBR. The objective of the study was to develop, characterize, and study the osteogenic potential of Gel-SiHA membrane for GBR.

Combining 10% propolis with carbonated hydroxyapatite to observe the RANKL expression in a rabbit’s alveolar bone

Background: Periodontitis causes an increased receptor activator level in the nuclear factor-κβ ligand (RANKL), which is one of the inflammatory mediators that plays a role in osteoclastogenesis. The open flap debridement (OFD) technique is the preferred treatment when accompanied by regenerative periodontal treatment using guided tissue regeneration (GTR) and guided bone regeneration (GBR). Carbonated hydroxyapatite is a GBR material that serves as a scaffold and has strong osteoconductive properties for bone regeneration. Propolis is natural product that can decrease osteoclastogenesis in periodontitis by decreasing the RANKL expression. Purpose: To investigate the RANKL expression after open flap debridement by applying carbonated hydroxyapatite to 10% propolis in the alveolar bone of rabbits. Methods: Nine induced-periodontitis rabbits (Oryctolagus cuniculus) were divided into three treatment groups of Group A OFD, Group B OFD followed by the application of carbonated hydroxyapatite, and Group C OFD followed by application of 10% propolis-carbonated hydroxyapatite. Each group was selected one to euthanised on the seventh, 14th and 28th day, respectively, and prepared using histology slides. The data was analysed using a two-way ANOVA followed by a post-hoc LSD test (p<0.05). Results: The RANKL expression in each group showed significant differences (p=0.00; p<0.05) on the seventh, 14th and 28th day. The post-hoc LSD test showed that the RANKL expression in the treatment group with carbonated hydroxyapatite-10% propolis had significant differences (p<0.05) in the intergroup analysis at different time points. Conclusion: Combining 10% propolis with carbonated hydroxyapatite in OFD treatment can decrease the RANKL expression in a rabbit’s alveolar bone.

Fabrication and Characteristics of PCL Membranes Containing Strontium-Substituted Hydroxyapatite Nanofibers for Guided Bone Regeneration.

Poly(ε-caprolactone) (PCL) membranes have been widely used in guided tissue regeneration (GTR) and guided bone regeneration (GBR). In addition, hydroxyapatite is the major inorganic component and an essential composition of hard bone and teeth. Recently, numerous studies have demonstrated that strontium-substituted hydroxyapatite (SrHA) not only enhances osteogenesis but also inhibits adipogenesis of mesenchymal stem cells. Therefore, SrHA incorporated into PCL could be an alternative material for GBR. In this study, strontium-substituted hydroxyapatite nanofibers (SrHANFs) were fabricated by a sol–gel route followed by electrospinning. We then fabricated PCL–SrHANF membranes as cell culture substrates and assessed the cellular behavior of osteoblast-like cells. Based on the observations of alkaline phosphatase (ALP) activity, bone sialoprotein (BSP) and osteocalcin (OCN) immunofluorescence staining, and Alizarin Red-S staining of cells cultured on the PCL–SrHANF and PCL membranes, we concluded that SrHANFs can promote the differentiation and mineralization of osteoblast-like cells and that PCL–SrHANF membranes have potential for GBR applications.

Development of a Photo-Crosslinking, Biodegradable GelMA/PEGDA Hydrogel for Guided Bone Regeneration Materials.

Gelatin-based hydrogel, which mimics the natural dermal extracellular matrix, is a promising tissue engineering material. However, insufficient and uncontrollable mechanical and degradation properties remain the major obstacles for its application in medical bone regeneration material. Herein, we develop a facile but efficient strategy for a novel hydrogel as guided bone regeneration (GBR) material. In this study, methacrylic anhydride (MA) has been used to modify gelatin to obtain photo-crosslinkable methacrylated gelatin (GelMA). Moreover, the GelMA/PEGDA hydrogel was prepared by photo-crosslinking GelMA and PEGDA with photoinitiator I2959 under UV treatment. Compared with the GelMA hydrogel, the GelMA/PEGDA hydrogel exhibits several times stronger mechanical properties than pure GelMA hydrogel. The GelMA/PEGDA hydrogel shows a suitable degradation rate of more than 4 weeks, which is beneficial to implant in body. In vitro cell culture showed that osteoblast can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA/PEGDA hydrogel had good cell viability and biocompatibility. Furthermore, by changing the quantities of GelMA, I2959, and PEGDA, the gelation time can be controlled easily to meet the requirement of its applications. In short, this study demonstrated that PEGDA enhanced the performance and extended the applications of GelMA hydrogels, turning the GelMA/PEGDA hydrogel into an excellent GBR material.

Integrated Oxidized-Hyaluronic Acid/Collagen Hydrogel with β-TCP Using Proanthocyanidins as a Crosslinker for Drug Delivery.

The susceptibility of guided bone regeneration (GBR) material to infection by pathogens at wound sites during bone healing has often been overlooked. The objective of this study was the synthesis and characterization of a potential material for antibacterial GBR application. In the current study, the mechanical strength and biocompatibility of a composite restoration material—made of oxidized hyaluronic acid (HA)/type I collagen hydrogel integrated with tricalcium phosphate (β-TCP) using a natural crosslinking agent, oligomeric proanthocyanidins (OPCs)—were evaluated. The suitability of the material as a carrier matrix for antibacterial applications was evaluated by following the drug-release profile of tetracycline loaded within the composite. Results indicated that this composite material had a high swelling ratio of 420% and mechanical strength of 25 kPa while remaining at more than 60% of the weight after 30 days of an in vitro degradation test with good biocompatibility in promoting the proliferation of MG-63 cells. Drug release studies further showed that 93% of the tetracycline was released after 5 days, which supports this GBR material’s capability to release antibacterial drugs while keeping other required GBR material design functions.

Carbon nanohorns accelerate bone regeneration in rat calvarial bone defect

A recent study showed that carbon nanohorns (CNHs) have biocompatibility and possiblemedical uses such as in drug delivery systems. It was reported that some kinds of carbonnanomaterials such as carbon nanotubes were useful for bone formation. However, theeffect of CNHs on bone tissue has not been clarified. The purpose of this study was toevaluate the effect of CNHs on bone regeneration and their possible application for guidedbone regeneration (GBR). CNHs dispersed in ethanol were fixed on a porouspolytetrafluoroethylene membrane by vacuum filtration. Cranial defects were created inrats and covered by a membrane with/without CNHs. At two weeks, bone formation underthe membrane with CNHs had progressed more than under that without CNHs andnumerous macrophages were observed attached to CNHs. At eight weeks, there was nosignificant difference in the amount of newly formed bone between the groups and theappearance of macrophages was decreased compared with that at two weeks. Newly formedbone attached to some CNHs directly. These results suggest that macrophages induced byCNHs are related to bone regeneration. In conclusion, the present study indicatesthat CNHs are compatible with bone tissue and effective as a material for GBR.

In Vitro and In Vivo Evaluation of a nHA/PA66 Composite Membrane for Guided Bone Regeneration

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.

Three‐layered membranes of collagen/hydroxyapatite and chitosan for guided bone regeneration

The purpose of this study was to design a novel hybrid membrane with optimized properties for guided bone regeneration (GBR). Both the top and bottom layers of the sandwich-structured membrane were composed of collagen containing 20 wt% hydroxyapatite (HA), while the middle layer was made of chitosan. The above three layers were formulated into an integral membrane from their respective slurries through a layer-by-layer filtration process. The phase and composition of the membrane were confirmed by FT-IR and XRD analyses. The observation of its morphology by SEM showed that the membrane had a porous structure and structural integrity. The chitosan layer ensured the high tensile strength and elastic modulus of the membrane, while the presence of the collagen/HA composite layers endowed it with good flexibility and bioactivity. These results suggest that the integrated membrane prepared in this study would have the potential for use as a GBR material.

Comparison of resorbable and nonresorbable guided bone regeneration material

Comparison of resorbable and nonresorbable guided bone regeneration material

The relationship among CD 4, CD 8, and MRC OX-12 antigen expression in 4NQO induced premalignant lesion of rat

The relationship among CD 4, CD 8, and MRC OX-12 antigen expression in 4NQO induced premalignant lesion of rat