Sustained Regeneration of Soft Tissue Defects

软组织缺损的持续再生

• 批准号: 8314234
• 负责人: Jonathan August Kluge
• 金额: $ 15万
• 依托单位: SPECTRASILK, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2013-08-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314234
• 关键词: Address; Adipose tissue; Animals; Biocompatible; Biocompatible Materials; Biological; Blood Vessels; Cell Adhesion; Cell Communication; Cells; Clinical; Clinical Trials; Collagen; Data; Defect; Disease; Drug or chemical Tissue Distribution; FDA approved; Fatty acid glycerol esters; Fibroins; Filler; Glycolates; Goals; Growth Factor; Human; Implant; Laminin; Measurement; Mechanics; Mus; Natural regeneration; Normal tissue morphology; Operative Surgical Procedures; Outcome; Outcome Assessment; Phase; Platelet-Derived Growth Factor; Polymers; Porosity; Positioning Attribute; Preparation; Process; Proteins; Rattus; Repeat Surgery; Role; Running; Sampling; Scaffolding Protein; Shapes; Silk; Site; Source; Structure; Supporting Cell; Surface; Surgical Flaps; System; Time; Tissues; Transplantation; Trauma; Vascular Endothelial Growth Factors; Vascularization; base; cancer surgery; clinically relevant; design; image processing; improved; in vivo; in vivo regeneration; lipid biosynthesis; meetings; polycaprolactone; preclinical study; programs; regenerative; restoration; scaffold; soft tissue; subcutaneous; time use; tissue reconstruction; tissue regeneration; vasculogenesis

DESCRIPTION (provided by applicant): Summary There is no clinical option to restore large soft tissue defects to normal tissue structure and function. Lipoaspriates and fat transfers offer some benefits, but retention of volume and avoidance of recurring repeats of the surgeries is a major problem for large defects, such as those from surgery and trauma. Thus, sustained (retention of volume during remodeling in vivo to normal restored tissue states) soft tissue reconstruction is a major unmet clinical need, with origins in disease, surgeries and trauma. All current clinical approaches, including surgical flaps, artificial fillers, and free fat transplant ll present significant limitations. In particular, these options fail to restore native tissue size, sape and function over extended time frames; losing volume within three months of surgery. Therefore there is a critical need for new options in the field that would restore large soft tissu defects in terms of retention of volume for at least one year during tissue integration and regeneration in vivo. To address this need, we propose to implement a 3D porous silk-based protein biomaterial scaffold system in combination with lipoaspirate. The unique features of the system include the ability to stabilize the silk protein matrix used in vivo for more than a year yt achieve full native tissue regeneration over time, the ability to support cells and promote adipogenesis and vasculogenesis, the mechanical robustness of the scaffold system to support tissue structure and volume over time, and the use of a biocompatible, FDA approved, biomaterial (silk) in the process. The hypothesis is that a biomaterial system can be designed for soft tissue reconstruction needs where size and shape at the implant site can be retained for at least one year during vascularized adipose formation, and allow full integration with native tissue with complete remodeling over time. Our comprehensive preliminary data support the feasibility of the plan and the aim is designed to demonstrate the best path forward in a three month in vivo mouse study. We will assess variables of cell adhesion sites (RGD), and the role of lipoaspirate in the process. Unseeded control scaffolds will also be studied. Outcomes will include assessments against other commonly considered biodegradable polymeric materials (collagen, PLGA, PCL): (a) retention of size and shape for 3 months in vivo, and (b) vascularized adipose tissue distribution in the scaffold, and (c) integration with surrounding tissue. At the end of the study we anticipate being in a position to pursue long term large animal studies and then human clinical trials. PUBLIC HEALTH RELEVANCE: The need for stable soft tissue reconstruction is large and growing due to severe trauma, diseases such as cancer and surgery. However, current clinical options are limited. The proposed program will address this need and fill the current gap in available clinical options in terms of retention of volume and shape of the defect site during tissue regeneration.

描述（由申请人提供）：总结没有将大的软组织缺损恢复到正常组织结构和功能的临床选择。脂肪移植和脂肪转移提供了一些好处，但保留体积和避免反复重复手术是大缺陷的主要问题，如手术和创伤。因此，持续的（在体内重塑至正常恢复的组织状态期间保持体积）软组织重建是主要未满足的临床需求，其起源于疾病、手术和创伤。目前所有的临床方法，包括外科皮瓣、人工填充物和游离脂肪移植都存在明显的局限性。特别是，这些选择无法在延长的时间范围内恢复天然组织大小，sape和功能;在手术后三个月内失去体积。因此，本领域迫切需要在体内组织整合和再生期间在体积保留方面恢复大的软组织缺损至少一年的新选择。为了满足这一需求，我们建议结合脂肪抽吸物实施3D多孔丝基蛋白质生物材料支架系统。该系统的独特特征包括稳定体内使用的丝蛋白基质超过一年的能力，随着时间的推移实现完全的天然组织再生，支持细胞和促进脂肪生成和血管生成的能力，支架系统随着时间的推移支持组织结构和体积的机械稳健性，以及在该过程中使用生物相容性的FDA批准的生物材料（丝）。假设生物材料系统可以设计用于软组织重建需求，其中在血管化脂肪形成期间植入部位的尺寸和形状可以保持至少一年，并且允许与天然组织完全整合，随着时间的推移完全重塑。我们全面的初步数据支持该计划的可行性，其目的是在为期三个月的体内小鼠研究中展示最佳前进路径。我们将评估细胞粘附位点（RGD）的变量，以及脂肪抽吸物在该过程中的作用。还将研究未接种的对照支架。结果将包括对其他通常认为的可生物降解聚合物材料（胶原、PLGA、PCL）的评估：（a）在体内3个月内保持尺寸和形状，（B）支架中血管化脂肪组织分布，以及（c）与周围组织的整合。在研究结束时，我们预计能够进行长期的大型动物研究，然后进行人体临床试验。 公共卫生关系：由于严重的创伤、癌症等疾病和手术，对稳定的软组织重建的需求很大，并且不断增长。然而，目前的临床选择有限。拟议的计划将满足这一需求，并填补目前的差距，在现有的临床选择方面的保留体积和形状的缺损部位在组织再生。