Hydrogel Scaffolds with Engineered Dynamically Tunable Topographies for hMSC Diff

描述（由申请人提供）：临床外科医生在重建先天性异常、创伤、感染和/或肿瘤切除导致的骨缺损时，选择的数量有限。目前的骨移植技术和材料都有局限性。出于这个原因，我的目标是通过研究人类间充质干细胞（hMSCs）如何从其微环境中接收信息，来改进从周围组织中招募细胞并促进成骨分化（自然骨再生过程的一部分）的植骨材料。地形线索已被证明影响细胞粘附、运动、增殖、蛋白质表达、基因调控和hMSCs的分化。Bowman-Anseth实验室开发的一种基于硫醇的光聚合方案将用于制造含有细胞粘附模拟物和酶和光可降解连接的生物材料，这种生物材料允许使用精确的空间侵蚀来创建地形。提出的研究旨在通过研究如何将地形线索纳入包含细胞粘附模拟物和酶降解连接的聚合物支架中来影响成骨分化，从而设计改进的植骨材料。我假设分化将取决于微环境的动态变化，这将通过光致化学来实现。本文概述了两个具体目标：目标1：确定促进间充质干细胞成骨分化的巯基聚合物支架的地形特征和空间排列。目的2：研究实时改变地形特征的空间排列对成骨分化的影响。这些目标的完成将大大促进我们对地形如何诱导MSC分化的机制的理解。这种聚合物系统和方法的多功能性使我们能够对hMSC培养进行独特的实验，并提高我们对材料系统的理解，这些材料系统可以很容易地用于基于干细胞传递或归巢的组织再生应用。

DESCRIPTION (provided by applicant): Clinical surgeons have a limited number of options when reconstructing bone defects that result from congenital anomalies, trauma, infection and/or oncologic resection. Current bone-graft implantation techniques and materials each have limitations. For this reason, I aim to improve bone grafting materials that will recruit cells from the surrounding tissue and promote osteogenic differentiation, part of the natural bone regeneration process, by investigating how human mesenchymal stem cells (hMSCs) receive information from their microenvironments. Topographic cues have been shown to influence cell adhesion, motility, proliferation, protein expression, gene regulation and differentiation of hMSCs. A thiol-ene based photopolymerization scheme developed in the Bowman-Anseth laboratories will be used to create biomaterials containing cell adhesion mimics and enzymatically and photo-degradable linkages that allow for the creation of topographies using precise spatial erosion. The proposed research aims to engineer improved bone grafting materials by investigating how incorporating topographic cues into a polymer scaffold that contains cell adhesion mimics and enzymatically degradable linkages influences osteogenic differentiation. I hypothesize that differentiation will depend on dynamic changes in their microenvironment that will be achieved through the photolabile chemistry. Two specific aims are outlined: Aim 1: Identify topographic features and spatial arrangements in thiol-ene polymer scaffolds that promote osteogenic differentiation of hMSCs. Aim 2: Examine the effects of changing the spatial arrangement of topographic features in real-time on osteogenic differentiation. Completion of these aims will significantly advance our understanding of the mechanisms for how topography induces MSC differentiation. The versatility of this polymer system and approach allows us to conduct unique experiments for hMSC culture and improve our understanding of material systems that can be easily tailored for tissue regeneration applications based on stem cell delivery or homing.