The combination of BCP and BMP2-cop.BioCaP showed a promising potential for guided bone regeneration clinically in the future.

Icariin, a typical flavonol glycoside, is the main active component of Herba Epimedii, which was used to cure bone-related diseases in China for centuries. It has been reported that Icariin can be delivered locally by biomaterials and it has an osteogenic potential for bone tissue engineering. Biomimetic calcium phosphate (BioCaP) bone substitute is a novel drug delivery carrier system. Our study aimed to evaluate the osteogenic potential when Icariin was internally incorporated into the BioCaP granules. The BioCaP combined with Icariin and bone morphogenetic protein 2 (BMP-2) was investigated in vitro using an MC3T3-E1 cell line. We also investigated its efficacy to repair 8 mm diameter critical size bone defects in the skull of SD male rats. BioCaP was fabricated according to a well-established biomimetic mineralization process. In vitro, the effects of BioCaP alone or BioCaP with Icariin and/or BMP-2 on cell proliferation and osteogenic differentiation of MC3T3-E1 cells were systematically evaluated. In vivo, BioCaP alone or BioCaP with Icariin and/or BMP-2 were used to study the bone formation in a critical-sized bone defect created in a rat skull. Samples were retrieved for Micro-CT and histological analysis 12 weeks after surgery. The results indicated that BioCaP with or without the incorporation of Icariin had a positive effect on the osteogenic differentiation of MC3T3-E1. BioCaP with Icariin had better osteogenic efficiency, but had no influence on cell proliferation. BioCap + Icariin + BMP-2 showed better osteogenic potential compared with BioCaP with BMP-2 alone. The protein and mRNA expression of alkaline phosphatase and osteocalcin and mineralization were higher as well. In vivo, BioCaP incorporate internally with both Icariin and BMP-2 induced significantly more newly formed bone than the control group and BioCaP with either Icariin or BMP-2 did. Micro-CT analysis revealed that no significant differences were found between the bone mineral density induced by BioCaP with icariin and that induced by BioCaP with BMP-2. Therefore, co-administration of Icariin and BMP-2 was helpful for bone tissue engineering.

AimTo evaluate the effect of bone morphogenetic protein 2 (BMP‐2) incorporated biomimetic calcium phosphate (BMP‐2/BioCaP) in conjunction with barrier membrane on periodontal regeneration in chronic periodontitis experimental model.Material and MethodsChronic periodontitis experimental model with critical‐sized supra‐alveolar defects was created in 15 dogs’ mandibles. After the initial periodontal therapy, the defects were randomly assigned to the following groups: (a) control; (b) barrier membrane; (c) deproteinized bovine bone mineral + barrier membrane; (d) BioCaP + barrier membrane and (e) BMP‐2/BioCaP + barrier membrane (6 quadrants with 18 teeth per group). Eight weeks later, clinical examinations, micro‐CT, and histomorphometric analyses were performed.ResultsClinical examinations, including plaque index, bleeding index, and probing depth, were similar for all groups. In contrast, the clinical attachment loss was significantly lower in defects grafted with BMP‐2/BioCaP and barrier membrane. The micro‐CT results showed that the height of mineralized tissue in defects grafted with BMP‐2/BioCaP and barrier membrane was significantly higher. For histometric analysis, the defects grafted with BMP‐2/BioCaP and barrier membrane exhibited significantly more connective tissue height, new cementum height, new bone height and area, as well as less down‐growth of junctional epithelium.ConclusionBMP‐2/BioCaP could be a promising bone substitute for periodontal regeneration.

Objective We hypothesized that a biomimetic calcium phosphate (CaP) coating which incorporates morphogenetic protein 2 (BMP‐2) on the deproteinized bovine bone (DBB) blocks could be used to enhance the vertical alveolar ridge augmentation for the one‐stage onlay surgery with simultaneous implants insertion. We aimed to test this hypothesis in vivo. Material and methods Beagles dogs were used for the study (n = 6 specimens per group). One month after building the edentulous animal model, 4 mm vertical alveolar bone loss were surgically created and four groups of blocks (W × L × H: 7 mm × 10 mm × 4 mm) were randomly fixed onto the reduced alveolar ridge by implants: (a) DBB blocks alone (negative control group); (b) DBB blocks with superficial adsorption of 50 μg BMP‐2 (ad.BMP‐2 group); (c) DBB blocks coated by biomimetic CaP coating which incorporates 50 μg BMP‐2 (inc.BMP‐2 group); and (d) autologous bone blocks (positive control group). After 3 months of healing, samples were harvested for micro‐CT and histomorphometric analyses. Results In histomorphometry, the inc.BMP‐2 group showed a significantly thicker (coronal‐apically) and wider (buccal‐lingually) augmented bone area, better bone‐to‐implant contact than the negative control group. In both the micro‐CT and histomorphometry, the inc.BMP‐2 group showed more mineralized tissue than the negative control group and the inc.BMP‐2 group also showed significantly more newly formed bone and residual grafts than the negative control group in the upper half of the blocks. In micro‐CT, the inc.BMP‐2 group showed significantly more bone‐to‐graft contact percentage than the ad.BMP‐2 group. In both micro‐CT and histomorphometry, the inc.BMP‐2 group showed significantly more percentage of mineralized tissue than the ad.BMP‐2 group. No significant differences were found between the inc.BMP‐2 group and the positive control group either in micro‐CT or in histomorphometry. Conclusions The DBB blocks with coating‐delivered BMP‐2 significantly enhanced the efficacy of vertical alveolar bone augmentation, compared with the unloaded blocks and blocks with adsorbed BMP‐2, in the one‐stage onlay surgery with simultaneous implant insertion.

Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal–regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading. Primary condylar chondrocytes were exposed to hydrostatic compressive forces (HCFs) of different magnitudes (0, 50, 100, 150, 200, and 250 kPa) for 2 h. We measured the viability, morphology, and apoptosis of the chondrocytes with different treatments as well as the gene, protein expression, and phosphorylation of mechanosensitivity-related molecules, such as integrin α2, integrin α5, integrin β1, FAK, ERK, and PI3K. HCFs could significantly increase the viability and surface area of condylar chondrocytes and decrease their apoptosis in a dose-dependent manner. HCF of 250 kPa resulted in a 1.51 ± 0.02-fold increase of cell viability and reduced the ratio of apoptotic cells from 18.10% ± 0.56% to 7.30% ± 1.43%. HCFs could significantly enhance the mRNA and protein expression of integrin α2, integrin α5, and integrin β1 in a dose-dependent manner, but not ERK1, ERK2, or PI3K. Instead, HCF could significantly increase phosphorylation levels of FAK, ERK1/2, and PI3K in a dose-dependent manner. Cilengitide, the potent integrin inhibitor, could dose-dependently block such effects of HCFs. HCFs enhances the viability and decreases the apoptosis of condylar chondrocytes through the integrin-FAK-ERK/PI3K pathway.