Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering
Tailoring the degradation of hydrogels formed from multivinyl poly(ethylene glycol) and poly(vinyl alcohol) macromers for cartilage tissue engineering
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DOI：
10.1021/bm025666v
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发表时间：
2003-03-01
影响因子：
6.2
通讯作者：
Anseth, KS
中科院分区：
文献类型：
--
作者：
Martens, PJ;Bryant, SJ;Anseth, KS
调整聚合物细胞载体的降解曲线以匹配细胞和组织的生长是（软骨）组织工程的重要设计参数。在这项研究中，由二乙烯基四官能聚乙二醇（PEG）和多乙烯基多官能聚乙烯醇（PVA）大分子单体制备可降解水凝胶，形成均聚物和共聚物凝胶。这些凝胶的特征在于其体积溶胀比和质量损失曲线作为降解时间的函数。通过改变大分子单体的化学性质和功能，降解时间从均聚物 PVA 凝胶的不到 1 天变为纯 PEG 凝胶的 34 天。此外，降解介质影响质量损失，并且当使用含有胎牛血清的软骨细胞特异性介质时，观察到PEG凝胶的降解时间从34天显着缩短至12天。有趣的是，当形成 PEG 和 PVA 的共聚物凝胶时，PVA 在整个降解过程中释放（通过凝胶渗透色谱法测定），这表明通过与 PEG 大分子共聚促进了网络中 PVA 的共价交联。为了评估这些新型凝胶在软骨组织工程中的应用，将软骨细胞光封装在共聚物网络中并在体外培养长达 6 周。 DNA、糖胺聚糖 (GAG) 和总胶原蛋白含量随着培养时间的延长而增加，并且在 6 周时产生的新软骨组织从组织学角度来看分布均匀。生化分析显示，6 周时，构建体包含 0.66 +/- 0.04 微克 DNA/mg 湿重 (ww)、1.0 +/- 0.05% GAG/ww 和 0.29 +/- 0.07% 总胶原蛋白/ww。此外，随着新软骨组织的进化和凝胶的降解，在培养过程中压缩模量从 7 kPa 增加到 97 kPa。总之，通过 PEG 和 PVA 大分子单体共聚制备水凝胶是封装软骨细胞、控制凝胶降解曲线和生成软骨组织的有效工具。
Tuning the degradation profiles of polymer cell carriers to match cell and tissue growth is an important design parameter for (cartilage) tissue engineering. In this study, degradable hydrogels were fabricated from divinyl, tetrafunctional poly(ethylene glycol) (PEG) and multivinyl, multifunctional poly(vinyl alcohol) (PVA) macromers to form homopolymer and copolymer gels. These gels were characterized by their volumetric swelling ratio and mass loss profiles as a function of degradation time. By variation of the macromer chemistry and functionality, the degradation time changed from less than I day for homopolymer PVA gels to 34 days for pure PEG gels. Furthermore, the degrading medium influenced mass loss, and a marked decrease in degradation time, from 34 to 12 days, was observed with the PEG gels when a chondrocyte-specific medium containing fetal bovine serum was employed. Interestingly, when copolymer gels of PEG and PVA were formed, PVA was released throughout the degradation (as determined by gel permeation chromatography) suggesting that covalent cross-linking of the PVA in the network was facilitated by copolymerizing with the PEG macromer. To assess these novel gels for cartilage tissue engineering applications, chondrocytes were photoencapsulated in the copolymer networks and cultured in vitro for up to 6 weeks. DNA, glycosaminoglycan (GAG), and total collagen contents increased with culture time, and the resulting neocartilaginous tissue at 6 weeks was homogeneously distributed as seen histologically. Biochemical analysis revealed that the constructs were comprised of 0.66 +/- 0.04 mug of DNA/mg wet weight (ww), 1.0 +/- 0.05% GAG/ww, and 0.29 +/- 0.07% total collagen/ww at 6 weeks. Furthermore, the compressive modulus increased during culture from 7 to 97 kPa as the neocartilaginous tissue evolved and the gel degraded. In summary, fabricating hydrogels through the copolymerization of PEG and PVA macromers is an effective tool for encapsulating chondrocytes, controlling gel degradation profiles, and generating cartilaginous tissue.