The Optimization Research Of Bone Tissue Engineering Application Value

Objective: Study the construction strategy and implant manner of tissue engineering bone graft,to improve the construction efficacy of tissue engineering bone graft and the bone regeneration efficiency of seed cells;Investigate the feasibility of repair bone defect using off-the-shelf bone tissue engineering technique under pathological condition like osteoporosis,diabetes,and agedness,to extend its application range.Methods: 1.DBM microcarriers were prepared by smashing,sieving,freeze drying in sequence.Then Rat BMSCs were dynamicly seeded onto DBM-MC and commercial microcarriers Cytodex 3 in bioreactors.After dynamicly expanded and osteo-induced,both two microcarriers were mixed with calcium alginate and injected subcutaneously into rat.Finally,the constructed micro TEBG based on DBM-MC were injected into rat cranial defects to test its osteogenesis ability.2.Fetal rabbit BMSCs were expanded in vitro and mixed with alginate and 3D printing PCL scaffolds to repair the rabbit radius defects,being wrapped with 3D pringting PCL membranes to prevent fibrous tissue taking up defect area.Then osteodifferentiated BMSCs were injected into defect area under X ray.3.Rabbit osteoporosis mode was estabilished using hydrocortisone.28 days old fetal rabbit BMSCs were isolated,expanded and then seeded onto DBM.After osteodifferetiation,radius defect was created in castrate rabbits and repaired by TEBG.4.Fetal goat BMSCs,goat umlibical core MSC,Adult goat BMSCs were separated respectively,then seeded onto DBM.9-10 years old goats were bought and having cranial defect repair treatment.5.Diabetes Rat mode was made by intraperitoneal injection of STZ.IFG>11.1M rats were selected as diabetes rats.Then new borned SD rats BMSC were isolated and seed onto DBM.Femur defect mode was created and repaired with these TEBG.Results: 1.Compared with cytodex 3,DBM-MC have similar cell expansion ability.And its well osteogenesis as TEBG scaffolds was investigated in ectopic bone formatin mode.Meanwhile,micro TEBG based on DBM-MC could be used as injectable treatment to repair rat cranial defects.2.At 1 month time point,there is clear bony connection in 3+3 group,while 6+0 group have no shadows in defect area in X ray images.At 3 months,radius defects were succssefully repaired in 3+3 group and 6+0 group?The average bone volume of 3+3 group is higher than 6+0 group,yet with no significance was found.3.At 3months,OVX group have a compromise repair effect while non-OVX group regenerated more bone volume.\ 4.At 6months,all young goats` cranial defects were entirely repaired with all three seed cells.But there is hardly any bony tissue found in aged goats` cranial defects.5.At 3 months,only non-diabetes rats formed bony tissue in defect area;While at 6 months,diabetes rats groups showed bony tissue formed,.Conclusion: 1.The integrated construction strategy based on DBM-MC was a potential novel method for injectable bone tissue engineering.2.The two-step tissue engineering bone construction method is feasible.And large bone defect could be repaired using this method.3.The off-the-shelf bone tissue engineering strategy could be used to treat bone defects under osteoporosis.However,the repair effllsect was compromised.4.All TEBG constructed by different seed cells could fully repair the young goat cranial defects,but failed to repair aged goats defects.5.The repair of diabetes rat femur defects is slower than non-diabetes group using TEBG.