Optimize Fat Grafting for Craniofacial Soft Tissue

优化颅面软组织脂肪移植

• 批准号: 7026461
• 负责人: Stephen B Baker
• 金额: $ 7.58万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7026461
• 关键词: adipose tissue; angiogenesis; angiogenesis factor; athymic mouse; blood circulation; cell differentiation; clinical research; cytotoxicity; homologous transplantation; human subject; oral facial restoration; therapy design /development; tissue /cell preparation

DESCRIPTION (provided by applicant): Reconstruction of soft tissue defects is the major technical challenge for the craniofacial surgeon in the repair of cleft lip, hemifacial microsomia, and other disfiguring head and face congenital disorders. While free fat grafts are theoretically the ideal solution, their use has been plagued by graft resorption that results in suboptimal and disappointing outcomes. Fat graft resorption rates vary from 30-70%, requiring repetitive surgeries in an effort to reconstruct the child's face. Numerous clinical strategies have been used with inconsistent success to limit fat graft resorption. None of these approaches have yielded improved clinical outcomes; rigorous experimental analysis has not been conducted, and, most importantly, the mechanisms underlying fat graft resorption have never been investigated. We are conducting the first systematic investigation of the underlying biologic mechanism of fat graft resorption and mechanisms that might modulate resorption. Using an established animal model of human adipose tissue implanted into nude mice, our interdisciplinary research group employs immunochemical, molecular biological, and advanced imaging techniques to serially examine graft resorption and the molecular events that drive this process. Our first Aim is to systematically investigate the different clinical techniques available to harvest fat grafts, in order to determine the effects of graft handling on cell viability and biology. Our second Aim is to evaluate our leading hypothesis on fat graft resorption: determining the importance of an adequate blood supply to graft survival. We will investigate whether implanted grafts receive sufficient blood supply to sustain their survival, and then evaluate the effects of pro-angiongenic interventions. Our final Aim is geared to understand the role of adipocyte cell biology in fat graft resorption. Since adipocyte cell lineage differentiation status can change in implanted grafts, we will explore the contribution of this mechanism in graft failure. This project is the first systematic investigation of the mechanisms that underlie a major clinical obstacle in reconstructive surgery. Through this research project we hope to generate data that will seed larger, interdisciplinary research in this field.

描述（由申请人提供）：软组织缺陷的重建是颅面外科医生在修复唇裂，半身微粒细胞感以及其他毁容头和面部先天性疾病方面的主要技术挑战。虽然理论上是理想的解决方案，但自由脂肪移植是由于移植物吸收而困扰着它们的使用，从而导致次优和令人失望的结果。脂肪移植物吸收率从30-70％不等，需要重复手术以重建孩子的脸。许多临床策略已被用于限制脂肪移植吸收的不一致的成功。这些方法均未产生改善的临床结果。严格的实验分析尚未进行，最重要的是，从未研究过脂肪移植物吸收的机制。 我们正在对脂肪移植吸收和可能调节吸收的机制的潜在生物学机制进行首次系统研究。使用植入裸鼠的人脂肪组织的既定动物模型，我们的跨学科研究组采用免疫化学，分子生物学和先进的成像技术来串行检查移植物吸收和驱动该过程的分子事件。我们的第一个目的是系统地研究可用于收获脂肪移植物的不同临床技术，以确定移植物处理对细胞生存能力和生物学的影响。我们的第二个目的是评估我们关于脂肪移植物吸收的主要假设：确定足够的血液供应对移植物生存的重要性。我们将调查植入的移植物是否接受足够的血液供应以维持其生存，然后评估促血管基因干预的影响。我们的最终目标旨在了解脂肪细胞生物学在脂肪移植物吸收中的作用。由于脂肪细胞细胞谱系分化状态可能会改变植入的移植物，因此我们将探讨该机制在移植物衰竭中的贡献。该项目是对重建手术中主要临床障碍的机制的首次系统研究。通过该研究项目，我们希望生成将在该领域播种更大的跨学科研究的数据。