Department of Bioengineering, Rice University, 6500 Main Street, Houston, TX 77030, United States of America.
Department of Statistics, Rice University, 6100 Main Street, Houston, TX 77005, United States of America.
J Control Release. 2020 Dec 10;328:710-721. doi: 10.1016/j.jconrel.2020.09.048. Epub 2020 Sep 30.
This work investigated the effect of poly(l-lysine) (PLL) molecular weight and concentration on chondrogenesis of cocultures of mesenchymal stem cells (MSCs) and articular chondrocytes (ACs) in PLL-loaded hydrogels. An injectable dual-network hydrogel composed of a poly(N-isopropylacrylamide)-based synthetic thermogelling macromer and a chondroitin sulfate-based biological network was leveraged as a model to deliver PLL and encapsulate the two cell populations. Incorporation of PLL into the hydrogel did not affect the hydrogel's swelling properties and degradation characteristics, nor the viability of encapsulated cells. Coculture groups demonstrated higher type II collagen expression compared to the MSC monoculture group. Expression of hypertrophic phenotype was also limited in the coculture groups. Histological analysis indicated that the ratio of MSCs to ACs was an accurate predictor of the degree of long-term chondrogenesis, while the presence of PLL was shown to have a more substantial short-term effect. Altogether, this study demonstrates that coculturing MSCs with ACs can greatly enhance the chondrogenicity of the overall cell population and offers a platform to further elucidate the short- and long-term effect of polycationic factors on the chondrogenesis of MSC and AC cocultures.
本研究考察了聚赖氨酸(PLL)分子量和浓度对骨髓间充质干细胞(MSCs)和关节软骨细胞(ACs)共培养物在 PLL 负载水凝胶中软骨形成的影响。利用一种可注射的双网络水凝胶,由基于聚(N-异丙基丙烯酰胺)的合成温敏大分子和基于硫酸软骨素的生物网络组成,作为递送 PLL 和包封两种细胞群的模型。PLL 的掺入不会影响水凝胶的溶胀性能和降解特性,也不会影响包封细胞的活力。共培养组与 MSC 单培养组相比,Ⅱ型胶原蛋白表达更高。肥大表型的表达也在共培养组中受到限制。组织学分析表明,MSC 与 AC 的比例是长期软骨形成程度的准确预测因子,而 PLL 的存在显示出更显著的短期效果。总的来说,这项研究表明,将 MSCs 与 AC 共培养可以极大地提高整体细胞群体的软骨形成能力,并为进一步阐明阳离子因素对 MSC 和 AC 共培养物软骨形成的短期和长期影响提供了一个平台。