Biphasic Nanofiber-based Scaffold for Tendon-to-Bone Integration

用于肌腱与骨整合的双相纳米纤维支架

• 批准号: 7645643
• 负责人: HELEN H LU
• 金额: $ 17.31万
• 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 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7645643
• 关键词: Address; Age; Alkaline Phosphatase; Anabolism; Anatomy; Arts; Biochemical; Biological; Biomimetics; Calcified; Cell Culture Techniques; Cell-Matrix Junction; Cells; Characteristics; Clinical; Coculture Techniques; Collaborations; Collagen; Complex; Dental Inlays; Development; Devices; Engineering; Environment; Exercise; Failure; Fiber; Fibroblasts; Fibrocartilages; Generations; Growth; Healed; Heterogeneity; Histocompatibility Testing; Hydroxyapatites; In Vitro; Incidence; Inferior; Injury; Knowledge; Lead; Maintenance; Mechanics; Methodology; Methods; Minerals; Modeling; Morphology; Musculoskeletal; Nanotechnology; Natural regeneration; Nature; Nude Rats; Orthopedic Fixation Devices; Osteoblasts; Phase; Phenotype; Physiological; Procedures; Property; Public Health; Publishing; Qualifying; Reporting; Research; Research Personnel; Rotator Cuff; Rupture; Shoulder; Site; Solutions; Stimulus; System; Tendon structure; Testing; Tissue Engineering; Tissue Grafts; Tissues; Translations; United States; Variant; Work; base; biodegradable polymer; bone; bone healing; calcium phosphate; cell type; design; healing; high risk; humerus; in vivo; injured; innovation; mineralization; nanofiber; nanoparticle; poly(lactide); repaired; response; sample fixation; scaffold; soft tissue; subcutaneous; supraspinatus muscle

DESCRIPTION (provided by applicant): Nanotechnology-driven tissue engineering strategies are evaluated here for the development of innovative methods aimed at the biological fixation of soft tissue grafts. Specifically, we focus on the challenge of tendon-to-bone integration for Rotator Cuff repair and augmentation. Rotator cuff tear is the most common shoulder injury, with over 75,000 repair procedures performed annually in the US. Our approach to biological fixation centers on the regeneration of the anatomic insertion site between tendon and bone. Given the characteristic spatial variation in cell type, matrix composition and mineral content inherent at the native insertion site, it is expected that interface regeneration will require multiple cell types and a stratified scaffold capable of supporting multi-tissue formation. We have therefore developed a biomimetic, nanofiber-based biphasic scaffold for tendon-bone integration, with each of the phases designed for the formation of the non-mineralized and mineralized regions of the native insertion site. The objective of this proposal is to optimize multi-cell culture and biomimetic scaffold design parameters for interface regeneration and multi-tissue formation. Aim 1 will test the hypothesis that fibroblast and osteoblast response on the nanofiber-based scaffold will be governed by nanofiber geometry and mineral content. Aim 2 will focus on the formation of distinct yet continuous regions of non-calcified and calcified tissue regions on the biphasic scaffold through co-culture of fibroblasts and osteoblasts, as well as the maintenance of these distinct regions in vivo. Our effort to regenerate the anatomic fibrocartilage interface as part of rotator cuff repair represents an innovative solution to a significant clinical challenge. Moreover, the nanofiber-based multiphasic scaffold design and co-culture methods proposed here are highly original. It is anticipated that the successful completion of the proposed studies will facilitate the development of a new generation of integrative fixation devices, as well as demonstrating the potential of nanotechnology for engineering complex musculoskeletal tissue systems that can integrate seamlessly with the body. Biological fixation of the Rotator Cuff tendon grafts to bone poses a significant clinical challenge. This project focuses on the design and optimization of a biomimetic, nanofiber-based scaffold for promoting tendon-to-bone integration post cuff repair, focusing on exercising spatial control of fibroblasts and osteoblasts distribution and multi-tissue formation through multi-phased scaffold design and fibroblast-osteoblast co-culture. Findings from the planned studies will have a significant impact in public health due to the large number of Rotator Cuff repair procedures performed nationally and worldwide. In addition, this project can have broad impact in 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）：纳米技术驱动的组织工程策略在这里进行评估，以开发创新的方法，旨在生物固定软组织移植物。具体来说，我们关注肌腱-骨整合对肩袖修复和增强的挑战。肩袖撕裂是最常见的肩部损伤，在美国每年有超过75,000例修复手术。我们的生物固定方法集中在肌腱和骨之间解剖插入部位的再生。考虑到细胞类型、基质组成和天然插入部位固有的矿物质含量的特征空间变化，预计界面再生将需要多种细胞类型和能够支持多种组织形成的分层支架。因此，我们开发了一种用于肌腱-骨整合的仿生纳米纤维双相支架，每个阶段都设计用于形成原生插入部位的非矿化和矿化区域。本研究的目的是优化多细胞培养和仿生支架设计参数，用于界面再生和多组织形成。目的1将验证成纤维细胞和成骨细胞对纳米纤维支架的反应将由纳米纤维几何形状和矿物质含量决定的假设。Aim 2将重点关注通过成纤维细胞和成骨细胞的共培养，在双相支架上形成不同但连续的非钙化和钙化组织区域，以及这些不同区域在体内的维持。我们努力重建解剖纤维软骨界面，作为肩袖修复的一部分，代表了一种创新的解决方案，以应对重大的临床挑战。此外，本文提出的基于纳米纤维的多相支架设计和共培养方法具有很强的创新性。预计这些研究的成功完成将促进新一代综合固定装置的发展，并展示纳米技术在工程复杂肌肉骨骼组织系统方面的潜力，这些系统可以与身体无缝集成。生物固定肩袖肌腱移植物骨是一个重大的临床挑战。本项目重点设计和优化一种促进袖带修复后肌腱-骨融合的仿生纳米纤维支架，重点通过多阶段支架设计和成纤维-成骨细胞共培养，对成纤维细胞和成骨细胞分布和多组织形成进行空间控制。由于在国家和世界范围内进行了大量的肩袖修复手术，计划研究的结果将对公共卫生产生重大影响。此外，该项目可以通过移植物相互结合以及与宿主环境结合形成复杂的组织系统，从而在组织工程移植物向临床环境的转化方面产生广泛的影响。

项目成果

Engineering complex orthopaedic tissues via strategic biomimicry.

• DOI: 10.1007/s10439-014-1190-6
• 发表时间: 2015-03
• 期刊: Annals of biomedical engineering
• 影响因子: 3.8
• 作者: Qu D;Mosher CZ;Boushell MK;Lu HH
• 通讯作者: Lu HH

Tissue engineering strategies for the regeneration of orthopedic interfaces.

• DOI: 10.1007/s10439-010-0046-y
• 发表时间: 2010-06
• 期刊: ANNALS OF BIOMEDICAL ENGINEERING
• 影响因子: 3.8
• 作者: Lu, Helen H.;Subramony, Siddarth D.;Boushell, Margaret K.;Zhang, Xinzhi
• 通讯作者: Zhang, Xinzhi

Polymer fiber-based models of connective tissue repair and healing.

• DOI: 10.1016/j.biomaterials.2016.10.013
• 发表时间: 2017-01
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Lee NM;Erisken C;Iskratsch T;Sheetz M;Levine WN;Lu HH
• 通讯作者: Lu HH

The guidance of stem cell differentiation by substrate alignment and mechanical stimulation.

通过底物比对和机械刺激对干细胞分化的引导。

• DOI: 10.1016/j.biomaterials.2012.11.012
• 发表时间: 2013-03
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Subramony, Siddarth D.;Dargis, Booth R.;Castillo, Mario;Azeloglu, Evren U.;Tracey, Michael S.;Su, Amanda;Lu, Helen H.
• 通讯作者: Lu, Helen H.