Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo.
Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo.
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DOI：
10.1016/j.biomaterials.2011.05.033
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发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
--
作者：
Bian, Liming;Zhai, David Y.;Tous, Elena;Rai, Reena;Mauck, Robert L.;Burdick, Jason A.
间充质干细胞（MSCs）被认为是软骨修复的一种可行的细胞来源，转化生长因子 -β（TGF -β）超家族成员是MSC软骨形成的关键介质。虽然TGF -β介导的MSC软骨形成在体外颗粒或水凝胶培养中已得到充分证实，但临床转化将需要在体内有效地递送TGF -β。在此，我们研究了将含有TGF -β3的藻酸盐微球与人MSCs共同包封在透明质酸（HA）水凝胶中，以开发用于软骨修复的可植入构建体。与未涂层的微球相比，纳米膜涂层的藻酸盐微球中包封的TGF -β3显示出初始突释显著减少，释放时间延长至6天。接种有MSCs和含TGF -β3微球的HA水凝胶构建体与在培养基中持续补充TGF -β3的构建体相比，具有相当的力学性能和软骨基质含量，而将TGF -β3直接包封在凝胶中而无微球的构建体性能较差。当皮下植入裸鼠时，含有TGF -β3微球的构建体比不含TGF -β3或直接将TGF -β3添加到凝胶中的组形成更优的软骨基质。然而，皮下植入8周后，在植入的构建体中观察到钙化。为了防止这种情况，我们尝试将甲状旁腺激素相关蛋白（PTHrP）与TGF -β3共同递送至藻酸盐微球中，结果钙化部分减少。这项研究表明，TGF -β3的局部控制递送对于MSC形成新软骨至关重要，并且需要进一步优化以避免软骨诱导的MSCs向肥大表型分化。
Mesenchymal stem cells (MSCs) are being recognized as a viable cell source for cartilage repair and members of the transforming growth factor-beta (TGF-β) superfamily are a key mediator of MSC chondrogenesis. While TGF-β mediated MSC chondrogenesis is well established in in vitro pellet or hydrogel cultures, clinical translation will require effective delivery of TGF-βs in vivo. Here, we investigated the co-encapsulation of TGF-β3 containing alginate microspheres with human MSCs in hyaluronic acid (HA) hydrogels towards the development of implantable constructs for cartilage repair. TGF-β3 encapsulated in alginate microspheres with nanofilm coatings showed significantly reduced initial burst release compared to uncoated microspheres, with release times extending up to 6 days. HA hydrogel constructs seeded with MSCs and TGF-β3 containing microspheres developed comparable mechanical properties and cartilage matrix content compared to constructs supplemented with TGF-β3 continuously in culture media, whereas constructs with TGF-β3 directly encapsulated in the gels without microspheres had inferior properties. When implanted subcutaneously in nude mice, constructs containing TGF-β3 microspheres resulted in superior cartilage matrix formation to groups without TGF-β3 or with TGF-β3 added directly to the gel. However, calcification was observed in implanted constructs after 8 weeks of subcutaneous implantation. To prevent this, the co-delivery of parathyroid hormone-related protein (PTHrP) with TGF-β3 in alginate microspheres was pursued, resulting in partially reduced calcification. This study demonstrates that the controlled local delivery of TGF-β3 is essential to neocartilage formation by MSCs and that further optimization is needed to avert the differentiation of chondrogenically induced MSCs towards a hypertrophic phenotype.
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发表时间：
2009-02-20
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
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作者：
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影响因子：
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发表时间：
2000-06-01
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