Interaction between host cells and multicomponent material matrix

描述（由申请人提供）：生物过程（即治疗）在多组分层次结构中运行。为了加强材料生物相容性和组织工程中细胞过程的基础工程知识，阐明宿主细胞的结构-功能关系和控制机制至关重要。我们的目标是建立一种临床相关的多功能结构，提供几种发育信号，以增强宿主细胞在重建正常组织结构中的理想反应。此外，该结构为我们研究可溶性和固定化生物活性因子影响细胞功能的机制提供了一个微环境平台。材料的物理化学性质对这种介导的细胞行为的作用将与生物活性因子的传递一起确定。我们将使用模型细胞类型来选择宿主对生物材料反应的关键阶段（即，用于炎症的巨噬细胞，用于肉芽和纤维化的成纤维细胞，以及用于正常实质细胞终末期愈合的角化细胞）和模型可溶性和固定化因子（即，生长因子和细胞外基质蛋白衍生肽）作为研究时间依赖性，材料调节的生物反应的平台。我们的具体目标是：(1)开发一种原位光聚合互穿网络（IPN）系统，该系统由改性明胶和聚乙二醇衍生物组成，并含有可溶性（即角质细胞生长因子）和固定化（即纤维连接蛋白衍生的寡肽）生物功能因子。(2)利用单培养和二元细胞培养系统，建立对上述可溶性和固定化因子对模型细胞类型（即人血源性巨噬细胞、真皮成纤维细胞和角质形成细胞）激活的独立和加性作用的机制理解。(3)确定IPN在体内调节宿主反应和愈合的作用。

DESCRIPTION (provided by applicant): Biological processes (i.e., healing) operate at a multi-component hierarchy. To strengthen the fundamental engineering knowledge of cellular processes for material biocompatibility and tissue engineering, the elucidation of structure-function relationships and control mechanisms of host cells is critical. Our objective is to establish a clinically relevant multifunctional construct that provides several developmental signals to enhance the desirable response of host cells in the reestablishment of normal tissue architecture. Furthermore, this construct provides a microenvironment platform for us to study the mechanisms of soluble and immobilized bioactive factors on affecting cell function. The role of material physicochemical properties on this mediated cell behavior will be ascertained in tandem with the delivery of bioactive factors. We will employ model cell types for selected critical stages of host response to biomaterials (i.e., macrophages for inflammation, fibroblasts for granulation and fibrosis, and keratinocytes for end-stage healing by normal parenchymal cells) and model soluble and immobilized factors (i.e:, growth factors and extracellular matrix protein-derived peptides) as a platform in the study of time-dependent, material- modulated biological response. Our specific aims are: (1) To develop an in situ photopolymerizable interpenetrating network (IPN) system that consists of modified gelatin and polyethyleneglycol derivatives and contains soluble (i.e., keratinocyte growth factors) and immobilized (i.e., fibronectin derived oligopeptides) biofunctional factors. (2) To establish a mechanistic understanding of the independent and additive effect of aforementioned soluble and immobilized factors on the activation of model cell types (i.e., human blood-derived macrophages, dermal fibroblasts, and keratinocytes) using monoculture and binary cell culture systems. (3) To ascertain IPN efficacy in vivo in modulating the host reaction and healing.