School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China.
Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
J Control Release. 2017 Sep 10;261:234-245. doi: 10.1016/j.jconrel.2017.07.008. Epub 2017 Jul 8.
Localized and long-term delivery of growth factors has been a long-standing challenge for stem cell-based tissue engineering. In the current study, a polymeric drug depot-anchoring hydrogel scaffold was developed for the sustained release of macromolecules to enhance the differentiation of stem cells. Self-assembling peptide (RADA16)-modified drug depots (RDDs) were prepared and anchored to a RADA16 hydrogel. The anchoring effect of RADA16 modification on the RDDs was tested both in vitro and in vivo. It was shown that the in vitro leakage of RDDs from the RADA16 hydrogel was significantly less than that of the unmodified drug depots (DDs). In addition, the in vivo retention of injected hydrogel-incorporated RDDs was significantly longer than that of hydrogel-incorporated unmodified DDs. A model drug, vascular endothelial growth factor (VEGF), was encapsulated in RDDs (V-RDDs) as drug depot that was then anchored to the hydrogel. The release of VEGF could be sustained for 4weeks. Endothelial progenitor cells (EPCs) were cultured on the V-RDDs-anchoring scaffold and enhanced cell proliferation and differentiation were observed, compared with a VEGF-loaded scaffold. Furthermore, this scaffold laden with EPCs promoted neovascularization in an animal model of hind limb ischemia. These results demonstrate that self-assembling hydrogel-anchored drug-loaded RDDs are promising for localized and sustained drug release, and can effectively enhance the proliferation and differentiation of resident stem cells, thus lead to successful tissue regeneration.
局部和长期的生长因子输送一直是基于干细胞的组织工程的一个长期挑战。在当前的研究中，开发了一种聚合物药物库锚定水凝胶支架，用于大分子的持续释放，以增强干细胞的分化。制备了自组装肽（RADA16）修饰的药物库（RDD）并锚定到 RADA16 水凝胶上。测试了 RADA16 修饰对 RDD 在体外和体内的锚定效果。结果表明，RDD 从 RADA16 水凝胶中的体外泄漏明显少于未修饰的药物库（DD）。此外，体内注射水凝胶结合的 RDD 的保留时间明显长于水凝胶结合的未修饰 DD。将模型药物血管内皮生长因子（VEGF）包封在 RDD（V-RDD）中作为药物库，然后将其锚定到水凝胶上。VEGF 的释放可以持续 4 周。将内皮祖细胞（EPC）培养在 V-RDD 锚定支架上，与负载 VEGF 的支架相比，观察到细胞增殖和分化增强。此外，该支架负载 EPC 可促进动物后肢缺血模型中的新血管生成。这些结果表明，自组装水凝胶锚定的载药 RDD 具有局部和持续释放药物的潜力，并能有效增强驻留干细胞的增殖和分化，从而实现成功的组织再生。
