Development of engineered fasciocutaneous skin flaps

工程筋膜皮瓣的开发

基本信息

批准号：
10715063
负责人：
Basak Elif Uygun
金额：
$ 36.74万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-15 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10715063
关键词：
3-Dimensional Accounting Allografting Anatomy Animal Model Architecture Autologous Binding Biomaterials Research Blood Blood Vessels Blood capillaries Cell Density Cell fusion Cell-Matrix Junction Cells Chemicals Clinic Clinical Clinical Trials Complex Congenital Abnormality Cues Data Defect Deformity Dermal Development Elastin Endothelial Cells Endothelium Engineering Environment Extracellular Matrix Extravasation Face Feedback Fibroblasts Fibronectins Goals Growth Growth Factor Histologic Histology Immune Immunosuppression Inflammation Legal patent Liquid substance Malignant Neoplasms Medical Methods Modeling Molecular Morbidity - disease rate Patients Peptides Physiological Population Proliferating Protocols documentation Reconstructive Surgical Procedures Research Safety Scanning Shapes Site Skin Structure System Techniques Testing Tissue Engineering Tissues Transplantation Trauma Trees Vascularization Whole Blood Work X-Ray Computed Tomography blood perfusion cell growth cell type clinical translation clinically relevant design disability-adjusted life years dosage ex vivo perfusion global health immunogenicity in vivo keratinocyte novel protein aminoacid sequence public health relevance recruit repaired restoration scaffold soft tissue synergism thrombogenesis translational study vascular tissue engineering

项目摘要

ABSTRACT Deformities created by birth defects, trauma, inflammation, and medical conditions including cancer constitute a significant global health burden accounting for 11% of worldwide disability-adjusted life years and can be corrected by reconstructive surgery. Standard reconstructive techniques include autologous, pedicled or vascularized tissue flaps to replace moderate to severe composite tissue defects. Limitation of these methods include donor-site morbidity and difficulty in shaping the graft to restore complex three-dimensional anatomy. In the case of fasciocutaneous flaps, both factors are limiting – and a significant portion of such defects cannot be treated with current techniques. In the longer term, Vascularized composite allografts (VCAs) have potential to revolutionize the treatment of complex soft tissue absence by providing an anatomically exact tissue unit enabling like-for-like restoration, but is impractical as long as the recipient requires toxic immunosuppression which limited the number of VCA transplants to about 150 over the last 2 decades. Our long-term goal is to engineer vascular composite allografts using patient specific cells for repairing composite tissue defects. The goal of this project is to develop a novel protocol for creating fasciocutaneous flaps (FCF) that are vascularized and blood compatible, which would provide a straightforward path to treating some currently unfixable defects clinically in the short-term, while laying the groundwork for building more complex tissues in the long term. The rationale of the study is that while most past biomaterials research has focused on producing the ideal scaffold from the ground up using synthetic materials, the native extracellular matrix (ECM), de facto contains much of necessary architecture and environmental cues absent from synthetic matrices, and hence presents a promising, more realistic alternative approach for producing engineered tissue substitutes, which can vertically advance the field of tissue engineering.

抽象的由出生缺陷、创伤、炎症和癌症等医疗状况造成的畸形构成重大的全球健康负担，占全球残疾调整生命年的 11%，可以通过重建手术来矫正，标准重建技术包括自体重建、带蒂重建。或血管组织瓣来替代中度至重度复合组织缺陷。方法包括供体部位发病率和塑造移植物以恢复复杂三维的困难对于筋膜皮瓣来说，这两个因素都是限制因素——而且其中很大一部分因素是有限的。从长远来看，血管复合同种异体移植物无法治疗缺陷。（VCA）有可能通过提供一种治疗方法彻底改变复杂软组织缺失的治疗解剖学上精确的组织单元可以实现类似的修复，但只要接受者需要毒性免疫抑制，这将过去 2 年间 VCA 移植的数量限制在 150 例左右几十年。我们的长期目标是利用患者特异性细胞设计血管复合同种异体移植物进行修复该项目的目标是开发一种用于创建筋膜皮肤的新方案。有血管且血液相容的皮瓣（FCF），这将提供一种直接的治疗途径一些目前在临床上短期内无法修复的缺陷，同时为构建更多缺陷奠定基础该研究的基本原理是，虽然大多数过去的生物材料研究都具有长期的复杂组织。专注于使用合成材料（天然细胞外材料）从头开始生产理想的支架矩阵（ECM），事实上包含合成中缺少的许多必要的架构和环境线索基质，因此提出了一种有前途的、更现实的替代方法来生产工程组织替代品，可以垂直推进组织工程领域。