The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis
The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis
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DOI：
10.1016/j.biomaterials.2004.01.066
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发表时间：
2004-11-01
期刊：
影响因子：
14
通讯作者：
Galis, ZS
中科院分区：
文献类型：
--
作者：
Sung, HJ;Meredith, C;Galis, ZS
尽管生物可降解聚合物的降解产物在很大程度上是非细胞毒性的，但关于支架的降解速率相关的酸性副产物效应的详细信息很少。支架的体外和体内降解速率可以区分为快速降解聚合物(如聚D，L-乳酸-乙醇酸共聚物，PLGA，50：50)和慢降解聚合物(如，聚己内酯-聚己内酯，PCL)。我们应用了一种新的方法来制备厚度均匀的10微米厚的高孔支架，并利用盐析方法中盐和水的组合的相变特性，提出了一种带有运动平台的计算机控制的刀片式涂布机。然后，我们通过评估三维支架中培养的原代小鼠主动脉平滑肌细胞的活力，在体外验证了快速降解的效果。我们发现，细胞活力与降解率成反比，并依赖于从播种(上)表面到下表面海冰的深度。用荧光探针法测定培养基中的pH，发现PLGA支架内的pH随时间而降低，与PLGA降解相对应，并与细胞活力密切相关。植入小鼠背部皮下的支架的体内分析显示，PLGA和PCL在炎症和细胞侵袭方面存在显著差异。重要的是，这些与支架内功能性血管生成的程度相关。同样，PLGA支架表现出较少的细胞动员和较少的血管生成，进一步支持了生物相容性聚合物降解所造成的酸性环境的负面影响。(C)2004爱思唯尔有限公司。保留所有权利。
Even though degradation products of biodegradable polymers are known to be largely non-cytotoxic, little detailed information is available regarding the degradation rate-dependent acidic byproduct effect of the scaffold. In vitro and in vivo scaffold degradation rate could be differentiated rising a fast degrading polymer (e.g., poly D, L-lactic-glycolic acid co-polymer, PLGA, 50:50) and a slow degrading polymer (e.g., poly epsilon-caprolactone, PCL). We applied a new method to develop uniform 10 mum thickness of high porous scaffolds rising a computer-controlled knife coater with a motion stage and exploiting phase transition properties of a combination of salts and water in salt-leaching method. We then verified in vitro the effect of fast degradation by assessing the viability of primary Mouse aortic smooth muscle cell Cultured in the three-dimensional scaffolds. We found that cell viability was inversely related to degradation rate and was dependent on the depth from the seeding (upper) surface toward the lower surf ice. The pH measurement of Culture medium using fluorescence probes showed time-dependent decrease in pH in the PLGA scaffolds, corresponding to PLGA degradation, and closely related to cell viability. In vivo analysis of scaffolds implanted subcutaneously into the back of mice, showed significant differences in inflammation and cell invasion into PLGA vs. PCL. Importantly, these were correlated with the degree of the functional angiogenesis within the scaffolds. Again, PLGA scaffolds demonstrated less cell mobilization and less angiogenesis, further supporting the negative effect of the acidic environment created by the degradation of biocompatible polymers. (C) 2004 Elsevier Ltd. All rights reserved.