Repair of Soft Tissue Defects with Engineered Fat Grafts

描述(申请人提供)：这项研究的长期目标是开发一种临床可翻译的策略来修复由癌症、创伤、先天性畸形和感染引起的软组织缺陷。用组织工程化脂肪移植修复软组织缺损是避免目前重建手术中许多局限性的理想解决方案。然而，工程脂肪移植物如何存活的根本问题在很大程度上仍然没有答案。这项提议的直接目标是解决阻碍脂肪组织工程进展的三个基本问题。我们假设，工程脂肪的成功移植与移植物的细胞成分有关，移植物受体部位的微环境也进行了测试。利用综合的、多学科的方法研究这一假说有三个具体目标。目的1重点是确定注射器吸入的人类脂肪的细胞组成，作为用于处理采集的脂肪以供植入的技术的函数。流式细胞术被用来鉴定和量化细胞群体。在目标2中，我们确定了工程化脂肪移植物体积与局部血供的关系。这一关键的设计参数是使用定量组织形态计量学和异种移植模型来阐明的，该模型结合了具有自身带蒂血供的脂肪结构。目标3集中于确定招募常驻脂肪前体和干细胞的必要作用。工程脂肪移植物的发展将广泛影响与癌症、创伤、先天性畸形和感染引起的软组织缺陷相关的医疗保健。了解脂肪移植物所涉及的细胞群和脂肪移植物对血液供应的依赖性是影响工程脂肪移植物设计的关键机制。此外，脂肪移植部位成脂细胞的存在可能会影响脂肪移植的存活率。一旦了解了这些基本问题，就有可能为新的生物启发技术模仿或调整这些活动。

DESCRIPTION (provided by applicant): The long-term objective of this research is to develop a clinically translatable strategy to repair soft tissue defects resulting from cancer, trauma, congenital abnormalities, and infections. Repair of soft tissue defects with tissue engineered fat grafts are the ideal solution to obviate many current limitations in reconstructive surgery. However, the fundamental question of how engineered fat grafts survive remains largely unanswered. The immediate objective of this proposal is to address three fundamental issues that hinder the progress of adipose tissue engineering. We hypothesize that successful grafting of engineered fat is linked to the cellular composition of the graft and the microenvironment of the graft's recipient site is tested. Three specific aims investigate this hypothesis utilizing an integrated, multidisciplinary approach. Aim 1 focuses on defining the cellular composition of syringe-aspirated human fat as a function of the techniques used to process harvested fat for implantation. Flow cytometry is employed to identify and quantify cell populations. In Aim 2, we determine the relationship between engineered fat graft volume and local blood supply. This critical design parameter is elucidated using quantitative histomorphometry and a xenograft model that incorporates a fat construct possessing its own pedicled blood supply. Aim 3 concentrates on determining the requisite role of the recruitment of resident fat precursor and stem cells. The development of an engineered fat graft will broadly impact health care related to soft tissue defects caused by cancer, trauma, congenital abnormalities, and infections. Understanding the cell populations involved in fat grafting and blood supply dependence of fat grafts are critical mechanisms that affect the design of an engineered fat graft. Moreover, the involvement of resident adipogenic cells at the site of fat grafting may modulate the survival of fat grafting. These fundamental issues, once understood, offer the potential to mimic or modulate these activities for novel bioinspired technologies.