Arginine Contained Poly(Ester Urea) Urethanes And Their Halloysite Nanocomposites In Bone Repair

Thermoplastic polyurethanes(PUs)with segmented stuctures,are of excellent mechanical properties and good processability,applied in many fields like artificial blood vessels,pericardial patches and other substitutes for adjustable performance.But poor biodegradability,hydrophilicity and cytocompatibility are still exits which impedes the application as bone tissue repair or regenerative medicine materials.In this study,an amino-terminated bis(L-arginine)alkylene diester extender(L-Arg-x,x=2,4 6,8)was synthesized and biodegradable poly(ester urea)urethanes(PEUUs)with different content of arginine groups were designed,synthesized and characterized to improve the biodegradability,hydrophilicity and cytocompatibility of hydrophobic thermoplastic polyurethanes(TPUs)with PCL as soft segments.Halloysite Nanotubes(HNTs)were further composited to the polymers to further induce osteogenesis.The yields were increased as the x in L-Arg-x rising(yields increased from 17.63%to67.30%)and L-Arg-6 and L-Arg-8 were finally used for the polymeriazation of PEUUs.The resuls show that water contact angele decreased from 109.67±3.92~o to 59.10±0.61~o and Zeta potential increased from-20 mV to 130 mV(pH~7)as L-Arg-x increased.Besides,degradation was also improved,after a 60-day degradation,the weight loss increased to6%~30%rather than almost no degradation that showed in PU-BDO(<1%).None nontoxicity of all the synthesized polymers were confimed and Cytocompatibility was also improved that PEUU materials A8-1.2 and A8-1.6 were found to be suitable for human dental pulp stem cells(hDPSCs)to adhere,grow and proliferate on in vitro.aaterials A8-1.2 also induced proliferation and migration.Besides,their potential application for bone repair was also revealed by increased gene and protein levels of COL1 and BMP4.The compositon of PEUU and HNT improve mechanical properties of materials and well distribution was observed by a scanning electron microscope.The results also reveled that adding of HNTs could further enhance mineralization and osteogenic differentiation of hDPSCs in vitro,levels of COL1,BMP4 and RUNX2 remarkably increased on A8-1.2/6%HNTs.A rat cranial defect model was also built to assess the bone repair in vivo,osteointegration and repair were promoted in PEUUs implanted groups and 6%w/w HNT composited A8-1.2 showed best bone repair,BV/TV=(71.65±11.40)%.Macrophages were co-cultured with PEUUs and their HNTs composites,the changes in morphology and a variety of factors were evaluated to ensure the materials would not induce powerful immune responses that do harm to the bone repair process.The results showed no raised TNF-?level but increased IL-6,OSM and BMP2.Hence,in this study,amino-terminated bis(L-arginine)alkylene diesters and biodegradable Arg-PEUUs were successfully obtained.Biodegradability,hydrophilicity and cytocompatibility were effectively improved.The newly developed PEUU/HNT composites had ability to promote bone regeneration and might unlimite potential for bone repair.