Timmer Mark D, Shin Heungsoo, Horch R Adam, Ambrose Catherine G, Mikos Antonios G
Department of Bioengineering, Rice University, MS-142, Houston, Texas 77251-1892, USA.
Biomacromolecules. 2003 Jul-Aug;4(4):1026-33. doi: 10.1021/bm0300150.
This study evaluates the in vitro biocompatibility of an injectable and biodegradable polymeric network based on poly(propylene fumarate) (PPF) and the cross-linking agent PPF-diacrylate (PPF-DA). Using a methyl tetrazolium (MTT) assay, the effect of the concentrations of PPF and PPF-DA on the cytotoxicity of its unreacted macromers, cross-linked networks, and degradation products was examined. The influence of network structure properties on cell viability and attachment to the cross-linked material was also investigated. The unreacted macromers exhibited a time- and dose-dependent cytotoxic response that increased with more PPF-DA in the mixture. Conversely, the cross-linked networks formed with more PPF-DA did not demonstrate an adverse response because increases in conversion and cross-linking density prevented the extraction of toxic products. Fibroblast attachment was observed on the PPF/PPF-DA networks with the highest double bond conversions. The degradation products, obtained from the complete breakdown of the networks in basic conditions, displayed a dose-dependent cytotoxic response. These results show that there are concerns regarding the biocompatibility of injectable, biodegradable PPF/PPF-DA networks but also sheds light onto potential mechanisms to reduce the cytotoxic effects.
本研究评估了一种基于聚富马酸丙二醇酯（PPF）和交联剂PPF - 二丙烯酸酯（PPF - DA）的可注射且可生物降解的聚合物网络的体外生物相容性。使用甲基噻唑基四氮唑（MTT）测定法，研究了PPF和PPF - DA浓度对其未反应的大分子单体、交联网络及降解产物细胞毒性的影响。还研究了网络结构性质对细胞活力以及与交联材料附着的影响。未反应的大分子单体表现出时间和剂量依赖性的细胞毒性反应，混合物中PPF - DA含量越高，反应越强烈。相反，含有更多PPF - DA形成的交联网络未表现出不良反应，因为转化率和交联密度的增加阻止了有毒产物的析出。在双键转化率最高的PPF/PPF - DA网络上观察到了成纤维细胞的附着。在碱性条件下网络完全分解得到的降解产物显示出剂量依赖性的细胞毒性反应。这些结果表明，可注射、可生物降解的PPF/PPF - DA网络的生物相容性存在问题，但也揭示了降低细胞毒性作用的潜在机制。
