PEGylated poly(glycerol sebacate)-modified calcium phosphate scaffolds with desirable mechanical behavior and enhanced osteogenic capacity
PEGylated poly(glycerol sebacate)-modified calcium phosphate scaffolds with desirable mechanical behavior and enhanced osteogenic capacity
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聚乙二醇化聚癸二酸甘油酯修饰的磷酸钙支架具有理想的机械性能和增强的成骨能力
DOI：
10.1016/j.actbio.2016.08.023
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发表时间：
2016-10-15
影响因子：
9.7
通讯作者：
Liu, Changsheng
中科院分区：
文献类型：
--
作者：
Ma, Yifan;Zhang, Wenjing;Liu, Changsheng
磷酸钙（CaP）支架材料作为骨移植替代材料已得到广泛应用，但其力学性能和生物活性不理想，严重影响了其临床应用。为了解决这些问题，聚乙二醇化聚（癸二酸甘油酯）（PEGS），一种亲水性弹性体，在这项研究中，用于修改模型磷酸钙骨水泥（CPC）支架骨再生。合成了PEG含量为0%~ 40%的PEGS预聚物，并通过渗透和热交联的方法将其涂覆到CPC支架上。CPC/PEGS复合支架的抗压强度和韧性（定义为CPX/Y，X指PEGS中的PEG含量，Y指最终支架中的PEGS含量）随着涂层量和PEG含量的增加而有效地调整，CPX/Y表现出最佳的抗压强度为3.82 MPa，断裂伸长率为13.20%，与CPC相比提高了约5倍和3倍。以骨髓基质细胞为模型的体外细胞实验表明，包被和PEG修饰以剂量依赖的方式同步促进细胞贴壁和增殖。特别是，PEGS/CPC支架上的BMSCs的成骨分化强烈增强，尤其是对于CP 20/18。进一步的体内实验证实，PEGS/CPC诱导促进成骨，与CPC和PGS/CPC形成鲜明对比。结果表明，PEGS/CaP复合支架（涂层量为18%左右，PEG含量为20%~ 40%）具有良好的力学性能和细胞反应性，是一种理想的骨组织工程支架材料。本文以磷酸钙骨水泥（CPC）为模型材料，采用聚乙二醇化聚乙二醇（PEGS）聚合物对CPC进行改性。首次探索了PEGS和CaP基质多孔支架的这种仿生组合，而不影响其多孔结构。在这项研究中，CPC支架被赋予了强大的机械性能和促进生物活性，同时优化的聚合物涂层的量和PEG含量的PGS。在大鼠颅骨缺损修复中，PEGS/CPC的成骨效果进一步证明了其在骨组织再生中的应用潜力。本研究所提出的设计概念可能为未来组织工程材料的发展提供新的见解。(C)2016 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Calcium phosphate (CaP) scaffolds have been widely used as bone graft substitutes, but undesirable mechanical robustness and bioactivity greatly hamper its availability in clinic application. To address these issues, PEGylated poly (glycerol sebacate) (PEGS), a hydrophilic elastomer, was used to modify a model calcium phosphate cement (CPC) scaffold for bone regeneration in this study. The PEGS pre-polymer with PEG content from 0% to 40% was synthesized and was subsequently coated onto the pre-fabricated CPC scaffolds by facile infiltration and thermal-crosslink process. Compression strength and toughness of the CPC/PEGS composite scaffold (defined as CPX/Y, X referred to the PEG content in PEGS and Y referred to PEGS amount in final scaffold) were effectively tailored with increasing coating amount and PEG content, and CPX/Y exhibited an optimal compressive strength of 3.82 MPa and elongation at break of 13.20%, around 5-fold and 3-fold enhancement compared to the CPC. In vitro cell experiment with BMSCs as model indicated that coating and PEG-modified synchronously facilitated cell attachment and proliferation in a dose-dependent manner. Particularly, osteogenic differentiation of BMSCs on PEGS/CPC scaffold was strongly enhanced, especially for CP20/18. Further in vivo experiments confirmed that PEGS/CPC induced promoted osteogenesis in striking contrast to CPC and PGS/CPC. Collectively, hybrids scaffolds (around 18% coating amount and PEG content from 20% to 40%) with the combination of enhanced mechanical behavior and up-regulated cellular response were optimized and PEGS/CaP scaffolds can be deemed as a desirable option for bone tissue engineering.Statement of SignificanceInsufficient mechanical robustness and bioactivity still limit the availability of calcium phosphate (CaP) scaffolds in clinic application. Herein, calcium phosphate cement (CPC) scaffold, as a model CaP-matrix material, was modified with PEGylated PGS (PEGS) polymers by facile infiltration and thermal-crosslink process. Such biomimetic combination of PEGS and CaP-matrix porous scaffold was first explored, without affecting its porous structure. In this study, CPC scaffold was endowed with robust mechanical behavior and promoted bioactivity by simultaneously optimizing the amount of polymer coating and the PEG content in PGS. In rat critical-sized calvarial defects repairing, osteogenic efficacy of PEGS/CPC further demonstrated the potential for application in bone tissue regeneration. The design concept proposed in this study might provide new insights into the development of future tissue engineering materials. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.