DEVELOPMENT OF AN IN VITRO WOUND HEALING MODEL

这项研究项目的长期目标是增进我们对 伤口愈合的可能性。多学科的体外和体内研究将 描述细胞-基质相互作用及其在调节 皮肤修复。研究将集中在机制上。 再上皮化和纤维增生症。在接下来的5年里，我们的目标是 以下问题： 1.表皮黏附的激活是否受基底膜和 增长因素？我们将分析在表达式中发生的更改 表皮激活过程中的特异性整合素黏附受体 黏附和迁移。我们将确定基底膜和 转化生长因子-β调节表皮的活化 细胞黏附。 2.细胞黏附蛋白和生长因子对细胞生长的影响 收缩对结缔组织生物发生的调节？我们会 使用长期补充抗坏血酸的成纤维细胞培养作为体外培养 新型结缔组织生物发生模型。我们将研究监管的问题。 细胞外基质收缩对组织生物发生的影响 黏附蛋白(纤维连接蛋白和玻璃体连接蛋白)和血小板的释放 因子(转化生长因子-β和血小板衍生生长因子)。 3.收缩的胶原蛋白凝胶从张力中释放出来是如何调节的 细胞生长和生物合成活性？收缩的胶原蛋白凝胶 成纤维细胞将通过机械操作从张力中释放出来。 细胞形态和生物合成活性的后续变化将是 量过了。 4.含精氨酸-甘氨酸-谷氨酸(Arg-Gly-Glu，RGE)的胶原肽是否抑制伤口 宫缩？与I型胶原相对应的含RGE的多肽 将测试它们抑制胶原胶原凝胶的能力 体外收缩。最具活性的多肽将进行测试，以了解 它能在体内抑制全层伤口收缩。 5.黏附蛋白在伤口中的分布和活性 流质的？我们将使用几种类型的伤口液体：吸入性水泡，慢性 皮肤溃疡、烧伤和外科手术(乳房切除术)。粘附力的分布 不同创面液体中的蛋白质和纤维连接蛋白在创面组织中的蛋白分解 将对伤口进行分析。

The long term goal of this research project is to enhance our understanding of wound healing. Multidisciplinary, in vitro and in vivo studies will describe cell-matrix interactions and their function in the regulation of cutaneous repair. Research will focus on the mechanisms of re-epithelization and fibroplasia. During the next 5 years we aim to answer the following questions: 1. Is activation of epidermal adhesion regulated by basement membrane and growth factors? We will analyze changes that occur in the expression of specific integrin adhesion receptors during activation of epidermal adhesion and migration. We will determine if basement membrane and transforming growth factor beta (TGF-BETA) regulate activation of epidermal cell adhesion. 2. What are the effects of cell adhesion proteins and growth factors on contraction-mediated regulation of connective tissue biogenesis? We will use long term, ascorbate-supplemented, fibroblast cultures as an in vitro model of new connective tissue biogenesis. We will study the regulation of tissue biogenesis by extracellular matrix contraction under the influence of adhesion proteins (fibronectin and vitronectin) and platelet released factors (TGF-BETA and PDGF). 3.How does the release of contracted collagen gels from tension regulate cell growth and biosynthetic activity? Collagen gels contracted by fibroblasts will be released from tension by mechanical manipulation. Subsequent changes in cell morphology and biosynthetic activity will be measured. 4. Do arg-gly-glu (RGE)-containing collagen peptides inhibit wound contraction? RGE-containing peptides that correspond to collagen type I sequences will be tested for their ability to inhibit collagen gel contraction in vitro. The most active peptide will be tested to learn if it inhibits full thickness wound contraction in vivo. 5. What is the distribution and activity of adhesion proteins in wound fluid? We will use several types of wound fluid: suction blister, chronic skin ulcer, burn, and surgical (mastectomy). The distribution of adhesion proteins in the various wound fluids and proteolysis of fibronectin in the wounds will be analyzed.