Large-sized cranial bone defect repair presents a great challenge in the clinic.The ideal cranioplasty materials to realize the functional and cosmetic recovery of the defect must have sufficient mechanical support,ex...Large-sized cranial bone defect repair presents a great challenge in the clinic.The ideal cranioplasty materials to realize the functional and cosmetic recovery of the defect must have sufficient mechanical support,excellent biocompatibility,good osseointegration and biodegradability as well.In this study,a high-strength mineralized collagen(MC)bone scaffold was developed with biomimetic composition,microstructure and mechanical properties for the repair of sheep largesized cranial bone defects in comparison with two traditional cranioplasty materials,polymethyl methacrylate and titanium mesh.The compact MC scaffold showed no distinct pore structure and therefore possessed good mechanical properties.The strength and elastic modulus of the scaffold were much higher than those of natural cancellous bone and slightly lower than those of natural compact bone.In vitro cytocompatibility evaluation revealed that the human bone marrow mesenchymal stem cells(hBMSC)had good viability,attachment and proliferation on the compact MC scaffold indicating its excellent biocompatibility.An adult sheep cranial bone defect model was constructed to evaluate the performances of these cranioplasty materials in repairing the cranial bone defects.The results were investigated by gross observation,computed tomography scanning as well as histological assessments.The in vivo evaluations indicated that compact MC scaffold showed notable osteoconductivity and osseointegration with surrounding cranial bone tissues by promoting bone regeneration.Our results suggested that the compact MC scaffold has a promising potential for large-sized cranial bone defect repair.展开更多
Purpose: Low intensity pulsed ultrasound stimulation (LIPUS) has been clinically applied to promote bone fracture healing in the orthopedic field. Thus, it is likely that LIPUS also stimulates bone regeneration in bon...Purpose: Low intensity pulsed ultrasound stimulation (LIPUS) has been clinically applied to promote bone fracture healing in the orthopedic field. Thus, it is likely that LIPUS also stimulates bone regeneration in bone defects in the cranial-maxillofacial area. However, this has not been clearly proved. Furthermore, optimal time point and period of the application after the surgery has not been reported. The purpose of the present study was to evaluate the effect of LIPUS on bone regeneration in the rat parietal bone defects especially focusing on time and period of the application. Materials and Methods: Eighteen Wistar rats (14 weeks old) were divided into 6 groups: 5 experimental groups and a control group. Bone defect of 5 mm diameter was prepared on each side of the parietal bone and customized gelatin membranes were placed over the bone defects. LIPUS (160 mW/cm2, 15 min/day) was applied to the defect area with an active transducer externally in the experimental groups according to the schedules of the applications: Group 1 (day 6 - 12), group 2 (day 13 - 19), group 3 (day 20 - 26), group 4 (day 6 - 19) and group 5 (day 6 - 26). All the animals were sacrificed at 28 days. The defects were analyzed with micro CT and then histologically. Results: In Group 1, new bone formation was significantly promoted and the newly-formed bone was thick and matured compared to the one of the control group. In other experimental groups there were tendencies of stimulation of new bone formation;however, they were not statistically significant. Discussion and Conclusion: The present study demonstrated that amount of new bone formation in the bone defect depended on the time and period of LIPUS application. It has been suggested that application of LIPUS at an early healing period, the second week after the surgery, effectively accelerated new bone formation.展开更多
目的观察以胶原缓释重组人骨形成蛋白2(recom b inan t hum an bone m orphogenetic prote in 2,rhBM P-2)复合骨髓间充质干细胞(m arrow m esenchym a l stem ce lls,M SC s)及珊瑚构建的组织工程骨修复兔颅骨极限缺损的能力。方法新...目的观察以胶原缓释重组人骨形成蛋白2(recom b inan t hum an bone m orphogenetic prote in 2,rhBM P-2)复合骨髓间充质干细胞(m arrow m esenchym a l stem ce lls,M SC s)及珊瑚构建的组织工程骨修复兔颅骨极限缺损的能力。方法新西兰大白兔40只,制备颅骨极限缺损,按植入的修复物不同随机分为5组,每组8只。Ⅰ组:自体髂骨,为阳性对照组;Ⅱ组:珊瑚,为阴性对照组;Ⅲ组:rhBM P-2+珊瑚;Ⅳ组:胶原+rhBM P-2+珊瑚;Ⅴ组:M SC s+胶原+rhBM P-2+珊瑚。将其分别植入兔颅骨极限缺损处,术后8、16周行大体观察、X线片、HE染色及M asson三色染色法观察比较骨缺损修复的情况。结果术后Ⅴ组材料与Ⅰ组修复颅骨极限缺损的效果相近,缺损区大体标本可见骨样组织充填,硬度与周边骨质相近,并与周边骨质形成明显骨融合;X线阻射程度高,16周时达80.45%±2.52%;组织学观察为板层状结构的新骨组织,空白孔隙区较少。Ⅳ组修复效果次之,Ⅲ组材料成骨能力较弱,Ⅱ组大部为半透明的纤维薄膜,缺损区界限清晰。结论胶原是rhBM P-2适宜的缓释载体,胶原及M SC s对促进复合支架材料修复骨缺损有重要意义。以M SC s+胶原+rhBM P-2+珊瑚构建的组织工程骨可成为一种良好的骨缺损修复材料。展开更多
Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widel...Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widely proven to promote bone regeneration,their weak mechanical properties limit the clinical applications in cranioplasty.Herein,we applied two previously developed mineralized collagen-based bone scaffolds(MC),porous MC(pMC)and compact MC(cMC)to construct a biphasic MC composite bone scaffold(bMC)to repair the large-sized cranial bone defect in developing sheep.A supporting frame composed of cMC phase in the shape of tic–tac–toe structure was fabricated first and then embedded in pMC phase.The two phases had good interfacial bond,attributing to the formation of an interfacial zone.The in vivo performance of the bMC scaffold was evaluated by using a cranial bone defect model in 1-month-old sheep.The computed tomography imaging,X-ray scanning and histological evaluation showed that the pMC phase in the bMC scaffold,similar to the pMC scaffold,was gradually replaced by the regenerative bone tissues with comprehensively increased bone mineral density and complete connection of bone bridge in the whole region.The cMC frame promoted new bone formation beneath the frame without obvious degradation,thus providing appropriate mechanical protection and ensuring the structural integrity of the implant.In general,the sheep with bMC implantation exhibited the best status of survival,growth and the repair effect.The biphasic structural design may be a prospective strategy for developing new generation of cranioplasty materials to regenerate cranial bone defect in clinic.展开更多
基金supported by National Natural Science Foundation of China(No.51572144,81360164 and 81660214)111 Project(No.B17026)Beijing Nova Program(Z161100004916051)。
文摘Large-sized cranial bone defect repair presents a great challenge in the clinic.The ideal cranioplasty materials to realize the functional and cosmetic recovery of the defect must have sufficient mechanical support,excellent biocompatibility,good osseointegration and biodegradability as well.In this study,a high-strength mineralized collagen(MC)bone scaffold was developed with biomimetic composition,microstructure and mechanical properties for the repair of sheep largesized cranial bone defects in comparison with two traditional cranioplasty materials,polymethyl methacrylate and titanium mesh.The compact MC scaffold showed no distinct pore structure and therefore possessed good mechanical properties.The strength and elastic modulus of the scaffold were much higher than those of natural cancellous bone and slightly lower than those of natural compact bone.In vitro cytocompatibility evaluation revealed that the human bone marrow mesenchymal stem cells(hBMSC)had good viability,attachment and proliferation on the compact MC scaffold indicating its excellent biocompatibility.An adult sheep cranial bone defect model was constructed to evaluate the performances of these cranioplasty materials in repairing the cranial bone defects.The results were investigated by gross observation,computed tomography scanning as well as histological assessments.The in vivo evaluations indicated that compact MC scaffold showed notable osteoconductivity and osseointegration with surrounding cranial bone tissues by promoting bone regeneration.Our results suggested that the compact MC scaffold has a promising potential for large-sized cranial bone defect repair.
文摘Purpose: Low intensity pulsed ultrasound stimulation (LIPUS) has been clinically applied to promote bone fracture healing in the orthopedic field. Thus, it is likely that LIPUS also stimulates bone regeneration in bone defects in the cranial-maxillofacial area. However, this has not been clearly proved. Furthermore, optimal time point and period of the application after the surgery has not been reported. The purpose of the present study was to evaluate the effect of LIPUS on bone regeneration in the rat parietal bone defects especially focusing on time and period of the application. Materials and Methods: Eighteen Wistar rats (14 weeks old) were divided into 6 groups: 5 experimental groups and a control group. Bone defect of 5 mm diameter was prepared on each side of the parietal bone and customized gelatin membranes were placed over the bone defects. LIPUS (160 mW/cm2, 15 min/day) was applied to the defect area with an active transducer externally in the experimental groups according to the schedules of the applications: Group 1 (day 6 - 12), group 2 (day 13 - 19), group 3 (day 20 - 26), group 4 (day 6 - 19) and group 5 (day 6 - 26). All the animals were sacrificed at 28 days. The defects were analyzed with micro CT and then histologically. Results: In Group 1, new bone formation was significantly promoted and the newly-formed bone was thick and matured compared to the one of the control group. In other experimental groups there were tendencies of stimulation of new bone formation;however, they were not statistically significant. Discussion and Conclusion: The present study demonstrated that amount of new bone formation in the bone defect depended on the time and period of LIPUS application. It has been suggested that application of LIPUS at an early healing period, the second week after the surgery, effectively accelerated new bone formation.
文摘目的观察以胶原缓释重组人骨形成蛋白2(recom b inan t hum an bone m orphogenetic prote in 2,rhBM P-2)复合骨髓间充质干细胞(m arrow m esenchym a l stem ce lls,M SC s)及珊瑚构建的组织工程骨修复兔颅骨极限缺损的能力。方法新西兰大白兔40只,制备颅骨极限缺损,按植入的修复物不同随机分为5组,每组8只。Ⅰ组:自体髂骨,为阳性对照组;Ⅱ组:珊瑚,为阴性对照组;Ⅲ组:rhBM P-2+珊瑚;Ⅳ组:胶原+rhBM P-2+珊瑚;Ⅴ组:M SC s+胶原+rhBM P-2+珊瑚。将其分别植入兔颅骨极限缺损处,术后8、16周行大体观察、X线片、HE染色及M asson三色染色法观察比较骨缺损修复的情况。结果术后Ⅴ组材料与Ⅰ组修复颅骨极限缺损的效果相近,缺损区大体标本可见骨样组织充填,硬度与周边骨质相近,并与周边骨质形成明显骨融合;X线阻射程度高,16周时达80.45%±2.52%;组织学观察为板层状结构的新骨组织,空白孔隙区较少。Ⅳ组修复效果次之,Ⅲ组材料成骨能力较弱,Ⅱ组大部为半透明的纤维薄膜,缺损区界限清晰。结论胶原是rhBM P-2适宜的缓释载体,胶原及M SC s对促进复合支架材料修复骨缺损有重要意义。以M SC s+胶原+rhBM P-2+珊瑚构建的组织工程骨可成为一种良好的骨缺损修复材料。
基金financial support from the National Key R&D Program of China(2020YFC1107602)Shandong Province Key R&D Program of China(2019JZZY011106)the National Natural Science Foundation of China(No.81660214,81960238,82160250).
文摘Appropriate mechanical support and excellent osteogenic capability are two essential prerequisites of customized implants for regenerating large-sized cranial bone defect.Although porous bone scaffolds have been widely proven to promote bone regeneration,their weak mechanical properties limit the clinical applications in cranioplasty.Herein,we applied two previously developed mineralized collagen-based bone scaffolds(MC),porous MC(pMC)and compact MC(cMC)to construct a biphasic MC composite bone scaffold(bMC)to repair the large-sized cranial bone defect in developing sheep.A supporting frame composed of cMC phase in the shape of tic–tac–toe structure was fabricated first and then embedded in pMC phase.The two phases had good interfacial bond,attributing to the formation of an interfacial zone.The in vivo performance of the bMC scaffold was evaluated by using a cranial bone defect model in 1-month-old sheep.The computed tomography imaging,X-ray scanning and histological evaluation showed that the pMC phase in the bMC scaffold,similar to the pMC scaffold,was gradually replaced by the regenerative bone tissues with comprehensively increased bone mineral density and complete connection of bone bridge in the whole region.The cMC frame promoted new bone formation beneath the frame without obvious degradation,thus providing appropriate mechanical protection and ensuring the structural integrity of the implant.In general,the sheep with bMC implantation exhibited the best status of survival,growth and the repair effect.The biphasic structural design may be a prospective strategy for developing new generation of cranioplasty materials to regenerate cranial bone defect in clinic.
