In vitro cytocompatibility evaluation of poly(octamethylene citrate) monomers toward their use in orthopedic regenerative engineering  

作　　者：Chuying Ma Ethan Gerhard Qiaoling Lin Silun Xia April Dawn Armstrong Jian Yang 

机构地区：[1]Department of Biomedical Engineering,Materials Research Institute,The Huck Institutes of the Life Sciences,The Pennsylvania State University,University Park,PA 16802,USA [2]CATS College,Canterbury,Kent CT13LQ,UK [3]Department of Orthopaedics and Rehabilitation,College of Medicine,The Pennsylvania State University,Hershey,PA 17033,USA

出　　处：《Bioactive Materials》2018年第1期19-27,共9页生物活性材料（英文）

摘　　要：Citrate based polymer poly(octamethylene citrate)(POC)has shown promise when formulated into composite material containing up to 65 wt%hydroxylapatite(HA)for orthopedic applications.Despite significant research into POC,insufficient information about the biocompatibility of the monomers 1,8-Octanediol and Citrate used in its synthesis is available.Herein,we investigated the acute cytotoxicity,immune response,and long-term functionality of both monomers.Our results showed a cell-type dependent cytotoxicity of the two monomers:1,8-Octanediol induced less acute toxicity to 3T3 fibroblasts than Citrate while presenting comparable cytotoxicity to MG63 osteoblast-like cells;however,Citrate demonstrated enhanced compatibility with hMSCs compared to 1,8-Octanediol.The critical cytotoxic concentration values EC30 and EC50,standard for comparing cytotoxicity of chemicals,were also provided.Additionally,Citrate showed slower and less inhibitory effects on long-term hMSC cell proliferation compared with 1,8-Octanediol.Furthermore,osteogenic differentiation of hMSCs exposure to Citrate resulted in less inhibitory effect on alkaline phosphatase(ALP)production.Neither monomer triggered undesired pro-inflammatory responses.In combination with diffusion model analysis of monomer release from cylindrical implants,based on which the maximum concentration of monomers in contact with bone tissue was estimated to be 2.2
104 mmol/L,far lower than the critical cytotoxic concentrations as well as the 1,8-Octanediol concentration(0.4 mg/mL or 2.7 mmol/L)affecting hMSCs differentiation,we provide strong evidence for the cytocompatibility of the two monomers degraded from citrate-based composites in the orthopedic setting.

关 键 词：Biodegradable Poly(octamethylene citrate) CITRATE 1 8-Octanediol CYTOCOMPATIBILITY Osteogenic differentiation Surface erosion 

分 类 号：R32[医药卫生—人体解剖和组织胚胎学]