Self-assembling multidomain peptides tailor biological responses through biphasic release.
Self-assembling multidomain peptides tailor biological responses through biphasic release.
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DOI：
10.1016/j.biomaterials.2015.01.079
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发表时间：
2015-06
期刊：
影响因子：
14
通讯作者：
Hartgerink JD
中科院分区：
文献类型：
--
作者：
Kumar VA;Taylor NL;Shi S;Wickremasinghe NC;D'Souza RN;Hartgerink JD
将小分子和药物递送至组织是多种组织工程策略的支柱。与全身治疗方法相比，专注于局部药物输送的下一代治疗方法为治疗难治性愈合提供了更有效的方法。在这里，我们描述了一种新型多域肽水凝胶，它利用合成肽化学、超分子自组装和细胞因子递送来定制生物反应。这种材料是仿生材料，具有剪切应力恢复能力，并提供隔离细胞因子的纳米纤维基质。细胞因子释放的双相模式导致 THP-1 单核细胞和巨噬细胞的时空激活。此外，巨噬细胞-物质相互作用得到促进，而不会产生促炎环境。可注射支架的皮下植入显示，早在第 3 天，由细胞因子负载决定的巨噬细胞浸润和极化显着增加，第 14 天支架完全吸收。巨噬细胞相互作用和对肽复合物的反应促进了 (i) 单核细胞/巨噬细胞的募集，(ii) 免疫细胞持续驻留直至降解，以及 (iii) 促进促分辨率 M2 环境。我们的结果表明这种可注射细胞因子负载水凝胶支架在各种组织工程应用中的潜在用途。
Delivery of small molecules and drugs to tissues is a mainstay of several tissue engineering strategies. Next generation treatments focused on localized drug delivery offer a more effective means in dealing with refractory healing when compared to systemic approaches. Here we describe a novel multidomain peptide hydrogel that capitalizes on synthetic peptide chemistry, supramolecular self-assembly and cytokine delivery to tailor biological responses. This material is biomimetic, shows shear stress recovery and offers a nanofibrous matrix that sequesters cytokines. The biphasic pattern of cytokine release results in the spatio-temporal activation of THP-1 monocytes and macrophages. Furthermore, macrophage-material interactions are promoted without generation of a proinflammatory environment. Subcutaneous implantation of injectable scaffolds showed a marked increase in macrophage infiltration and polarization dictated by cytokine loading as early as 3 days, with complete scaffold resorption by day 14. Macrophage interaction and response to the peptide composite facilitated the (i) recruitment of monocytes/macrophages, (ii) sustained residence of immune cells until degradation, and (iii) promotion of a pro-resolution M2 environment. Our results suggest the potential use of this injectable cytokine loaded hydrogel scaffold in a variety of tissue engineering applications.