Interface Tissue Engineering for Soft Tissue-to-Bone Integration

软组织与骨整合的界面组织工程

• 批准号: 8271269
• 负责人: HELEN H LU
• 金额: $ 29.37万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8271269
• 关键词: Anatomy; Anterior Cruciate Ligament; Articular ligaments; Biochemical; Biological; Biomimetics; Cell Culture Techniques; Cells; Characteristics; Chondrocytes; Clinical; Coculture Techniques; Collaborations; Complex; Development; Devices; Environment; Fibroblasts; Fibrocartilages; Generations; Heterogeneity; Histocompatibility Testing; In Vitro; Knee; Lead; Ligaments; Maintenance; Mechanics; Mediating; Methods; Minerals; Modeling; Natural regeneration; Nature; Operative Surgical Procedures; Osteoblasts; Osteogenesis; Phase; Phenotype; Procedures; Property; Public Health; Qualifying; Research; Research Personnel; Site; Spatial Distribution; Stimulus; Stress; System; Technology; Tendon structure; Testing; Tissue Engineering; Tissues; Translations; Variant; Work; anterior cruciate ligament reconstruction; base; bone; calcium phosphate; cell type; design; experience; graft failure; hamstring; implantation; in vivo; in vivo Model; injured; innovation; insight; mineralization; novel; public health relevance; reconstruction; sample fixation; scaffold; soft tissue; success

DESCRIPTION (provided by applicant): The anterior cruciate ligament (ACL) is the most frequently injured knee ligament, with over 100,000 reconstruction surgeries performed annually. Currently, the biological fixation of soft tissue-based grafts for ACL reconstruction poses a significant clinical challenge. Our approach to biological fixation centers on the regeneration of the anatomic insertion site between soft tissue and bone. Given the characteristic spatial variation in cell type, matrix composition and mineral content inherent at the enthesis, it is expected that interface regeneration will require multiple cell types and a stratified scaffold capable of supporting multi-tissue formation. Therefore, we have developed a biomimetic, multi-phased scaffold consisting of three distinct yet continuous phases, each designed for the formation of the ligament, fibrocartilage or bone regions found at the ACL-to-bone insertion. The objective of this proposal is to optimize multi-cell culture and scaffold design parameters for interface regeneration and multi-tissue formation. Aim 1 will test the hypothesis that osteoblast-fibroblast interactions can promote chondrocyte-mediated fibrocartilage formation on the scaffold. Aim 2 will optimize scaffold phase-specific mineral content and distribution. Aim 3 will focus on the formation of four distinct yet continuous tissue regions (ligament, non-mineralized fibrocartilage, mineralized fibrocartilage, and bone) through the tri-culture of fibroblasts, chondrocytes and osteoblasts on the stratified scaffold. Aim 4 will determine whether these biomimetic tissue regions formed in vitro can be maintained in vivo. Our effort to regenerate the anatomic fibrocartilage interface on ACL reconstruction grafts represents an innovative departure from the traditional focus on the non-physiologic fibrocartilage found within the bone tunnel. Moreover, the multi-phased scaffold design and tri-culture methods proposed here for multi-tissue formation are highly original. It is anticipated that the successful completion of our studies will facilitate the development of a new generation of integrative fixation devices, and our findings can be applied to many other conditions in which soft tissue-to-bone integration is also critical. PUBLIC HEALTH RELEVANCE: Biological fixation of soft tissue-based grafts for Anterior Cruciate Ligament (ACL) reconstruction poses a significant clinical challenge. We propose that the regeneration of the soft tissue-to-bone interface is a prerequisite for the functional integration of biological and synthetic grafts for ACL reconstruction. This project focuses on the design and optimization of a novel biomimetic scaffold for interface tissue engineering, using both in vitro and in vivo studies. Findings from the planned studies will have a significant impact on public health due to the large number of ACL reconstruction procedures performed nationally and worldwide. In addition, this project can have broad impact for the translation of tissue engineered grafts to the clinical setting, by enabling the formation of complex tissue systems through graft integration with each other as well as with the host environment.

描述（由申请人提供）：前交叉韧带（ACL）是最常见的膝盖韧带，每年进行100,000多次重建手术。目前，用于ACL重建的软组织基于软组织的移植物的生物学固定构成了重大的临床挑战。我们的生物固定方法集中在软组织和骨骼之间的解剖插入部位的再生上。鉴于细胞类型的特征空间变化，矩阵组成和感情固有的矿物含量，预计接口再生将需要多种细胞类型和能够支撑多组织形成的分层支架。因此，我们开发了一个由三个不同但连续的阶段组成的仿生，多型脚手架，每个相都是为了形成韧带的形成，纤维球杆菌或ACL到骨插入处的骨骼区域。该建议的目的是优化界面再生和多组织形成的多细胞培养和脚手架设计参数。 AIM 1将检验以下假设：成骨细胞 - 成纤维细胞相互作用可以促进支架上的软骨细胞介导的纤维球杆菌形成。 AIM 2将优化脚手架特异性矿物含量和分布。 AIM 3将通过成纤维细胞，软骨细胞和分层的辅助剂的三个培养物，通过成纤维细胞，软骨细胞和成骨细胞的三个文化，将四个不同但连续的组织区域（韧带，非矿化纤维球杆菌，矿化纤维球杆菌和骨骼）形成。 AIM 4将确定是否可以在体内保持体外形成的这些仿生组织区域。我们在ACL重建移植物上再生解剖纤维球界界面的努力代表了与传统对骨隧道中发现的非生理纤维球病的关注。此外，这里提出的用于多组织形成的多型脚手架设计和三个文化方法是高度原始的。预计我们的研究的成功完成将有助于开发新一代的综合固定设备，我们的发现可以应用于软组织到骨整合也至关重要的许多其他条件。 公共卫生相关性：针对前交叉韧带（ACL）重建的软组织基于软组织的移植物的生物学固定构成了重大的临床挑战。我们建议，软组织到骨界面的再生是生物和合成移植物进行ACL重建的功能整合的先决条件。该项目着重于使用体外和体内研究的新型仿生支架的设计和优化。由于全国和全球执行的大量ACL重建程序，计划中的研究结果将对公共卫生产生重大影响。此外，该项目可以通过通过彼此以及与宿主环境形成复杂组织系统的形成，可以使组织工程移植物转换为临床环境产生广泛的影响。