Repair of Soft Tissue Defects with Engineered Fat Grafts

描述（由申请人提供）：本研究的长期目标是开发一种临床可转化的策略，以修复由癌症、创伤、先天性畸形和感染引起的软组织缺损。组织工程化脂肪移植修复软组织缺损是解决目前重建外科诸多局限性的理想方法。然而，工程脂肪移植物如何存活的基本问题在很大程度上仍然没有答案。该建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，成功移植的工程脂肪与移植物的细胞组成和移植物受体部位的微环境有关。三个具体目标调查这一假设利用综合的，多学科的方法。目标1的重点是定义的细胞组成的活检抽吸的人脂肪作为一个功能的技术，用于处理收获的脂肪植入。流式细胞术用于鉴定和定量细胞群。在目标2中，我们确定了工程化脂肪移植体积与局部血供之间的关系。使用定量组织形态学和异种移植模型阐明了这一关键设计参数，该模型包含具有自身带蒂血液供应的脂肪结构。目标3集中于确定居民脂肪前体细胞和干细胞的募集的必要作用。工程脂肪移植物的发展将广泛影响与癌症、创伤、先天性异常和感染引起的软组织缺陷相关的医疗保健。了解脂肪移植中涉及的细胞群和脂肪移植物的血液供应依赖性是影响工程脂肪移植物设计的关键机制。此外，脂肪移植部位的脂肪形成细胞的参与可能会调节脂肪移植的存活。这些基本问题，一旦理解，提供了潜在的模仿或调节这些活动的新型生物启发技术。

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.