Loading of erythropoietin on biphasic calcium phosphate bioceramics promotes osteogenesis and angiogenesis by regulating EphB4/EphrinB2 molecules.

Improving osteogenesis and angiogenesis using different cells and drugs is critical in the field of bone tissue engineering. Recent research has found that erythropoietin (EPO) plays an important role in both osteogenesis and angiogenesis. In this study, we grafted polydopamine and EPO onto the surface of biphasic calcium phosphate. The characterization and release property of the modified bioceramics were assessed. Cell proliferation, expression of osteoblastic and endothelial markers, and EphB4/EphrinB2 molecules were investigated while employing co-cultures of two different cells [rat vein endothelial cells (VECs) and rat bone marrow mesenchymal stromal cells (BMSCs)]. The modified bioceramics were finally implanted into the SD rats' femurs and followed by investigating the bone defect repair efficacy and the expression of EphB4/EphrinB2 molecules in vivo. The results indicated that the modified bioceramics could control the release of EPO continuously. The osteogenesis and angiogenesis were improved along with the increased expression of EphB4/EphrinB2 molecules. The expression of EphB4/EphrinB2 molecules was also significantly increased in vivo and the bone defect was repaired effectively. Overall, our findings demonstrated that EPO loading on biphasic calcium phosphate bioceramics could promote both osteogenesis and angiogenesis. The results suggest that EphB4/EphrinB2 may be crucial in the process. Graphical abstract.

Reconstruction of mandibular bone defects using biphasic calcium phosphate bone substitutes with simultaneous implant placement in mini-swine: A pilot in vivo study.

This study aimed to investigate implant osseointegration using a new strategy of biphasic calcium phosphate (BCP) bone substitutes with simultaneous implant placement in mandibular reconstruction. Additionally, the temporal transcriptional profile associated with the early biological processes during osseointegration was determined. BCP and hydroxyapatite (HA) bone substitutes with simultaneous implant placement were grafted into mandibular defects created in mini-swine. Radiographic, histological, and biochemical analyses were applied for evaluation of osseointegration effects at 4 months after the grafting procedure. Bone formation around the implant was assessed by the bone area percentage (BA%) and the bone-implant-contact percentage (BIC%). The biomechanical evaluation was performed by the implant pullout test and the removal torque test. Microarray technology was utilized for gene expression comparison analysis at day 14 postoperatively. Radiographic and histological observation indicated enhanced bone formation in the BCP group compared to the HA group. Histomorphometric analyses of BA% and BIC% as well as biochemical analyses of the maximal pull-out force and the ultimate shear strength were all significantly greater in the BCP group (p < 0.05). Transcriptional analysis at an early stage of osseointegration revealed that genes belonging to biological processes associated with cell proliferation, development, osteogenesis, angiogenesis, and neurogenesis as well as the osteogenesis-related TGF-ß/BMP and WNT signaling pathways were upregulated in the BCP group. In conclusion, the reconstruction of mandibular defects using BCP with simultaneous implant placement resulted in superior osseointegration effects. A number of candidate genes that were differentially expressed may contribute to the superior osseointegration effects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2071-2079, 2019.

Wnt and Notch signaling pathways in calcium phosphate-enhanced osteogenic differentiation: A pilot study.

Calcium phosphate (CaP) ceramics are being increasingly used to repair critical bone defect for biocompatibility, biosafety, porous structure and osteoinduction. Wnt and Notch signaling pathways are conservative and classic signaling pathways regulating osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). In this study, we evaluated the expression of Wnt, Notch signal pathways and osteogenic related genes of BMSCs with and without Wnt pathway inhibitor DKK1 on CaP ceramics in vitro by real-time RT-PCR. Also, we evaluated new bone formation after implantation of CaP ceramics in vivo. The in vitro culture displayed the expression of Wnt, Notch signaling pathways and osteogenic related genes was increased at first and then declined. After adding DKK1 to the culture, the expression was decreased. The in vivo implantation showed significant bone formation on CaP ceramics. These findings reveal that Wnt and Notch signaling pathways play important roles in the CaP-enhanced osteogenic differentiation but the mechanism of synergistic effect needs to be further explored. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 149-160, 2019.

One-Stage treatment for maxillofacial asymmetry with orthognathic and contouring surgery using virtual surgical planning and 3D-printed surgical templates.

PURPOSE: Asymmetry is one of the most common maxillofacial deformities. One-stage treatment for maxillofacial asymmetry with orthognathic and contouring surgery has been rarely reported. This retrospective study aims to investigate the feasibility of simultaneous orthognathic and facial bone contouring surgery with the help of virtual surgical planning and 3D-printed navigation templates for facial asymmetry. PATIENTS AND METHODS: From January 2012 to December 2015, 51 patients diagnosed with maxillofacial asymmetry received treatment of combined orthognathic and contouring surgery under the guidance of virtual surgical planning and 3D-printed templates. Photographs and measurements were taken before and after operation to evaluate the effectiveness of the treatment. RESULTS: Photographs and cephalometric analysis showed the asymmetry was effectively corrected. All patients were satisfied with the aesthetic results. CONCLUSION: This study suggested the clinical feasibility of simultaneous orthognathic and contouring surgery for the treatment of maxillofacial asymmetry. Virtual surgical planning and 3D-printed surgical templates enable the surgeons to plan and carry out the procedure more predictably and achieve satisfactory outcomes.

Virtual Surgical Planning Assisted Management for Three-Dimensional Dentomaxillofacial Deformities.

OBJECTIVE: Treatment of 3-dimensional dentomaxillofacial deformities remains a significant clinical challenge. This retrospective study aims to present the modalities of management for complex 3-dimensional dentomaxillofacial deformities with the assistance of virtual surgical planning (VSP) and 3-dimensional printed navigation templates. STUDY DESIGN: Ten patients diagnosed with complex 3-dimensional dentomaxillofacial deformities received treatment of combined orthodontics and orthognathic surgery. Various surgical techniques as well as bone graft and distraction osteogenesis were used under the guidance of VSP and 3-dimensional printed navigation templates according to the characteristics of each patient. Follow-up included clinical examination and studies of spiral computed tomography preoperatively and for an average of 12 months postoperatively. RESULT: The clinical outcomes of patients showed that VSP was successfully transferred to actual surgery in all the 10 patients. Three-dimensional dentomaxillofacial deformities were corrected significantly. Satisfactory profiles and occlusion were achieved. CONCLUSION: The management of 3-dimensional dentomaxillofacial deformities required comprehensive consideration and detailed surgical planning. Virtual surgical planning serves as a reliable assistance in the management of 3-dimensional dentomaxillofacial deformities.