Fundamental and clinical experts from Japan,Korea and China,warmly gathered on the beautiful ice and snow city—Changchun,the capital of Jilin Province,China—during 23-26 January 2015,to present their research findings and participated in discussion relating to progress in biomaterials,stem cells and bone tissue engineering.The International Symposium on Recent Trend of Biomaterials and Stem Cells for Bone Tissue Engineering(BTE 2015)was hosted by the Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,and co-organized by the Department of Orthopaedics,China-Japan Union Hospital,Jilin University.
In order to architecturally and functionally mimic native Extracellular Matrix (ECM), a novel micro/nano-fibrous scaffold of hydroxyapetite/poly(lactide-co-glycolide) (HA/PLGA) composite was successfully prepared by melt-spinning method. A porous three-dimensional scaffold fabricated by melt-molding particulate-leaching method was used as control. This kind of scaffold comprising both nanofiber and microfiber had an original structure including a nano-network favorable for cell adhe- sion, and a micro-fiber providing a strong skeleton for support. The microfibers and nanofibers were blended homogeneously in scaffold and the compression strength reached to 6.27 MPa, which was close to human trabecular bone. The typical mi- cro/nano-fibrous structure was more benefcial for the proliferation and differentiation of Bone Mesenehymal Stem Cells (BMSCs). The calcium deposition and Alkaline Phosphatase (ALP) activity were evaluated by the differentiation of BMSCs, and the results indicated that the temporary ECM was very beneficial for the differentiation of BMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, micro/nano-fibrous scaffold was used for the purpose of rapid bone remodeling in the defect area. The results showed that a distinct bony callus of bridging was observed at 12 weeks post-surgery and the expression of osteogenesis-related genes (bone-morphogenetic protein-2, Osteonectin, collagen-I) increased because of the ECM-like structure. Based on the results, the novel micro/nano-fibrous scaffold might be a promising candidate for bone tissue engi- neering.
The biodegradable porous composite scaffold, composed of poly(lactide-co-glycolide) (PLGA) and hydroxyapatite nanoparticles (n-HAP) surface-grafted with poly(L-lactide) (PLLA) (g-HAP) (g-HAP/PLGA), was fabricated using the solvent casting/particulate leaching method, and its in vivo degradation behavior was investigated by the intramuscular implantation in rabbits. The composite of un-grafted n-HAP/PLGA and neat PLGA were used as controls. The scaffolds had interconnected pore structures with average pore sizes between 137 μm and 148 μm and porosities between 83% and 86%. There was no significant difference in the pore size and porosity among the three scaffolds. Compared with n-HAP/PLGA, the thermo-degradation temperature (Tc) of g-HAP/PLGA decreased while its glass transition temperature (Tg) increased. The weight change, grey value analysis of radiographs and SEM observation showed that the composite scaffolds of g-HAP/PLGA and n-HAP/PLGA showed slower degradation and higher mineralization than the pure PLGA scaffold after the intramuscular implantation. The rapid degradation of PLGA, g-HAP/PLGA and n-HAP/PLGA occurred at 8-12 weeks, 12-16 weeks and 16-20 weeks, respectively. Compared with n-HAP/PLGA, g-HAP/PLGA showed an improved absorption and biomineralization property mostly because of its improved distribution of HAP nanoparticles. The levels of both calcium and phosphorous in serum and urine could be affected to some extent at 3-4 weeks after the implantation of g-HAP/PLGA, but the biochemical detection of serum AST, ALT, ALP, and GGT as well as BUN and CRE showed no obvious influence on the functions of liver and kidney.
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.