Development of engineered fasciocutaneous skin flaps

工程筋膜皮瓣的开发

• 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
• 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

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.

摘要 由出生缺陷、创伤、炎症和包括癌症在内的医疗条件造成的畸形 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的重建技术包括自体，带蒂 或血管化组织瓣来替换中度至重度复合组织缺损。这些限制 方法包括供体部位的发病率和难以成形移植物以恢复复杂的三维 解剖学在筋膜皮瓣的情况下，这两个因素都是限制性的-并且这种限制性因素的很大一部分 缺陷不能用现有技术处理。从长期来看，带血管的复合同种异体移植物 （VCAs）有可能通过提供一种治疗复杂软组织缺失的方法来彻底改变治疗方法。 解剖学上精确的组织单位，使类似的恢复，但不切实际，只要接受者 需要毒性免疫抑制，这限制了VCA移植的数量，在过去的2年中约为150例 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， 复合组织缺损本项目的目标是开发一种新的协议，创建筋膜皮肤 皮瓣（FCF）是血管化和血液相容，这将提供一个直接的途径，以治疗 一些目前无法修复的缺陷，在临床上在短期内，同时奠定基础，建设更多的 复杂的组织。这项研究的基本原理是，虽然过去的大多数生物材料研究 专注于使用合成材料从头开始生产理想的支架， 基质（ECM），事实上包含了许多必要的架构和环境线索缺乏合成 基质，因此提出了一种有前途的，更现实的替代方法，用于生产工程组织 替代品，这可以垂直推进组织工程领域。