CULTURED EPIDERMAL GRAFTS FOR BURN PATIENTS

我们实验室的研究集中在基础和临床方面 表皮生物学 研究的临床领域集中在 对世界内部内在因素的理解 可以促进或抑制正常伤口愈合的床。 我们有 还表明，培养的表皮同种异体移植物（CEA）可以成功地 冷冻保存用于长期储存，随后取回并用于 增强伤口愈合。 我们的基本工作集中在定义 表皮纤溶酶原激活物抑制剂-1（派-1）的作用 基质完整性和细胞与基质粘附的调节剂， 正常人角质形成细胞（NHK）在创伤后和创伤期间的迁移 再生成熟 我们发现在再生成熟过程中 派-1表达仅限于参与不同的细胞亚群， 表皮细胞，通过次级反应途径上调， 这种诱导是生长因子和底物依赖性的。 是 假设生长因子介导的派-1基因重编程 表达对正常的伤口修复过程至关重要。 的 我们联合研究的最终目的是了解 人角质形成细胞迁移和分化的机制 以应对伤害，并利用我们的知识来设计更多 最佳的生物伤口敷料，以进一步加强双方的愈合 部分和全层烧伤创面。 为此，我们将解决 以下目标：一。 为了评估动力学和分子机制 在人角质形成细胞中潜在的诱导派-1基因转录 对实验性单层创伤后特异性生长因子的反应。 二. 特异性干扰派-1合成的动力学和程度 在人类角质形成细胞中通过分子遗传操作， 评估派-1表达与确定的表皮细胞生长的相关性 与体外和体内“愈合”相关的状态转变; III. 进行一项关于使用CEA加速 全层损伤中3：1网状移植物间隙的愈合， 四. 目的：优化复合皮片移植技术， 猪模型，以进一步增强CEA在以下背景下的效用： 全厚度将愈合。

Studies in our laboratories have centered on basic and clinical aspects of epidermal biology. The clinical areas of investigation have focused on developing an understanding of the intrinsic factors within the would bed that can either enhance or inhibit normal wound healing. We have also shown that cultured epidermal allografts (CEAs) can be successfully cryopreserved for long term storage, subsequently retrieved and used to enhance the would healing. Our basic efforts focused on defining the role of epidermal plasminogen activator inhibitor type-1 (PAI-1), a regulator of matrix integrity and cell-to-matrix adhesion, in directed migration of normal human keratinocytes (NHKs) post-wounding and during regenerative maturation. We showed that during regenerative maturation PAI-1 expression is confined to participate subpopulations of distinct epidermal cells, is upregulated via a secondary response pathways and that this induction is growth factor and substrate-dependent. It is hypothesized that growth factor-mediated reprogramming of PAI-1 gene expression is critical to the normal process of would repair. The ultimate aim of our combined studies is to develop an understanding of the mechanisms governing human keratinocyte migration and differentiation in response to wounding and to utilize our knowledge to design more optimal biological would dressings to further enhance the healing of both partial and full thickness burn wounds. To do this, we will address the following aims: I. To assess both the kinetics and molecular mechanisms underlying induced PAI-1 gene transcription in human keratinocytes in response to specific growth factors upon experimental monolayer wounding. II. To specifically perturb the kinetics and extent of PAI-1 synthesis in human keratinocytes via molecular genetic manipulations in order to assess the relevance of PAI-1 expression to defined epidermal cell growth state transitions associated with 'healing' in vitro and in vivo; III. To conduct a randomized clinical study on the use of CEAs to accelerate the healing of 3:1 meshed graft interstices in full thickness injuries, IV. To optimize composite skin grafting techniques in a pre-clinical porcine model to further enhance the utility of CEAs in the context of full thickness would healing.