调控干细胞募集与分化的皮肤再生材料及其原位诱导毛囊再生性能研究

Skin appendages such as hair follicle and sweat gland are the basis of skin functions. The loss of skin appendages will influence the function of temperature regulation and secretion, and therefore the healing quality of the damaged skin. Therefore, it is the key point in the field of skin regeneration materials to realize the regeneration of skin appendages. Aiming at loss of hair follicle, one of skin appendages, the study of designing a skin regeneration material with the property to regenerate hair follicle is proposed. The skin regeneration material is designed under the principle of tissue induced strategy and the inspiration of the function of endogenous MSC on wound healing. Endowed with the properties of MSC homing and controlled differentiation, a skin regeneration material which can induce the regeneration of hair follicle in situ is constructed. To realize this hypothesis, the techniques to control the loading and release of the homing factors and differentiation factors, as well as the delivery system for the sequence release of the multi-factors to match the development of hair follicle, should be studied. Then, the effects of the chemical-physical properties of the skin regeneration material on the properties of MSC homing and differentiation, as well as the ability to induce the regeneration of hair follicle, are carefully investigated. By this study, the possibility of the tissue induced materials on the regeneration of the complex organ is proved.

附属器官（如毛囊、汗腺）是皮肤体温调节、分泌排汗等功能的基础，其缺失严重影响损伤皮肤的再生与重建，如何再生附属器官是皮肤再生材料研究的难点与关注重点。本项目针对皮肤毛囊（重要附属器官之一）缺失难题，以组织诱导再生为核心理念，以内源性MSC在创面修复过程中的作用机制为启示，提出以内源性MSC为诱导调控目标的材料设计思想。通过赋予材料对内源性MSC的高效募集和诱导分化性能，构建一种可原位诱导毛囊再生的新型皮肤再生材料，探索组织诱导再生材料在实现皮肤高层次再生的可行性。围绕内源性MSC的高效募集与可控诱导分化难题，建立募集因子和诱导分化因子的可控传递和活性保持技术，实现二者在材料中的一体化负载以及匹配毛囊再生过程的顺序释放，阐明材料组成与结构对内源性MSC募集和分化行为的关系及调控规律，制备兼具干细胞募集和诱导分化性能的新型皮肤再生材料，实现含附属器官（毛囊）皮肤的原位诱导再生。

近年来，具有多分化潜能的干细胞等被广泛应用于组织修复。间充质干细胞（MSCs）因其来源丰富、分离和培养方法成熟以及具有降低免疫排斥等优势，被认为是实现组织再生的重要干细胞之一。MSCs批量扩增是应用外源性MSCs组织修复的基础。然而，体外扩增干细胞存在复杂耗时、免疫原性、干性丢失和植入后存活率低等不足，极大地限制了外源性MSCs的应用。因此，发展基于内源性MSCs的新一代高性能组织诱导再生材料具有重要意义。. 结合前期研究基础，本项目针对组织缺损难题，以组织诱导再生为核心理念，以内源性MSCs在创面修复过程中的作用机制为启示，以内源性MSCs为诱导目标。本项目建立了趋化因子基质细胞衍生因子（SDF-1α）的活性保持和可控释放纳米拆开体系；筛选了2种干细胞特异性粘附和捕获分子，包括多肽EPLQLKM（E7）、核酸适配体Aptamer 19S（Apt19S），建立了特异性粘附分子的可控修饰技术。系统研究材料表面可控修饰干细胞特特异性粘附分子对干细胞原位捕获和干性维持性能的影响。发展了复合干细胞和基因活性物质的一体化皮肤修复材料，实现了含汗腺附属器官皮肤的原位诱导再生。构建了集募集、特异性捕获一体化的E7多肽和SDF-1α修饰的复合胶原支架，通过对内源性间充质干细胞的有效募集和高效特异性捕获，实现了子宫内膜再生和生育力重建，具有重要的临床价值。