Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds
Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds
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DOI：
10.1039/c0jm00868k
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
Kohn, Joachim
中科院分区：
文献类型：
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作者：
Magno, Maria Hanshella R.;Kim, Jinku;Kohn, Joachim
由脱氨基酪氨酷基-酪氨酸烷基醋（DTR）、脱氨基酪氨酷基-酪氨酸（DT）和聚（乙二醇）（PEG）的低分子量嵌段组成的聚碳酸醋=元共聚物是一类新的聚合物，其具有良好的工程性质，同时在体内也是可再吸收的。本研究首次评价了其（i）降解行为、（ii）体外细胞毒性和（iii）体内生物相容性。通过溶剂浇铸、致孔剂浸提和相分离技术的组合制备多孔组织工程支架。支架（>90%孔隙率）显示（i）具有小于20 μ m的微孔和200 μ m至400 μ m的大孔的双峰孔分布，（ii）高度互连和开放的孔结构，和（iii）高度组织化的微观结构，其中微孔沿着大孔的壁定向和排列。在体外（PBS，37 ℃）测定分子量（数均，M（n））和质量损失，持续长达28天。所有三种聚合物组合物都快速降解，并且在21天后仅保留其初始分子量的10%，而在28天期间的质量损失是聚合物组合物依赖性的。通过测量MC3T3.E1（亚克隆4）前成骨细胞的代谢活性，确定聚合物支架的体外生物相容性长达14天。结果显示，单层培养的细胞与所有测试的聚合物支架之间没有统计学差异。通过共聚焦显微镜和SEM观察到整个支架体积的稳健细胞附着。在12周时在临界尺寸缺损（CSD）兔颅骨模型中评价了再吸收支架的生物相容性，仅显示出最小的炎症反应。总体而言，本文报道的结果说明了酪氨酸衍生的聚碳酸酯三元共聚物在组织工程支架设计中的潜在效用。
Polycarbonate terpolymers consisting of desaminotyrosyl-tyrosine alkyl esters (DTR), desaminotyrosyl-tyrosine (DT), and low molecular weight blocks of poly(ethylene glycol) (PEG) are a new class of polymers that have good engineering properties while also being resorbable in vivo. This study is the first evaluation of their (i) degradation behavior, (ii) in vitro cytotoxicity, and (iii) in vivo biocompatibility. Porous, tissue engineering scaffolds were prepared by a combination of solvent casting, porogen leaching and phase separation techniques. The scaffolds (>90% porosity) displayed (i) a bimodal pore distribution with micropores of less than 20 mu m and macropores between 200 and 400 mu m, (ii) a highly interconnected and open pore architecture, and (iii) a highly organized microstructure where the micropores are oriented and aligned along the walls of the macropores. Molecular weight (number average, M(n)) and mass loss were determined in vitro (PBS at 37 degrees C) for up to 28 days. All three terpolymer compositions were fast degrading and retained only 10% of their initial molecular weight after 21 days, while mass loss during the 28 days was polymer composition-dependent. In vitro biocompatibility of the polymer scaffolds was determined up to 14 days by measuring metabolic activity of MC3T3.E1 (subclone 4) pre-osteoblasts. The outcome showed no statistical difference between cells cultured in monolayer and all tested polymer scaffolds. Robust cell attachment throughout the scaffold volume was observed by confocal microscopy and SEM. The biocompatibility of resorbing scaffolds was evaluated at 12 week in a critical sized defect (CSD) rabbit calvaria model and showed only a minimal inflammatory response. Overall, the results reported here illustrate the potential utility of tyrosine-derived polycarbonate terpolymers in the design of tissue engineering scaffolds.