Objective: A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapaUte (g-HA)/ poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogene...Objective: A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapaUte (g-HA)/ poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods: A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were ob- served by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results: After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HNPLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HNPLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HNPLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HNPLGA, while only fibrous tissues formed in PLGA. Conclusions: The incorporation of g-HA mainly im- proved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone for- mation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.展开更多
基金Project supported by the National Natural Science Foundation of China(Nos.51473164 and 51273195)the Joint Research Project of Chinese Academy of Sciences and Japan Society for the Promotion of Science(CAS-JSPS+1 种基金No.GJHZ1519)the International Science and Technology Cooperation Program of China(No.2014DFG52510)
文摘Objective: A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapaUte (g-HA)/ poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods: A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were ob- served by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results: After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HNPLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HNPLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HNPLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HNPLGA, while only fibrous tissues formed in PLGA. Conclusions: The incorporation of g-HA mainly im- proved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone for- mation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.