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）：此处评估了纳米技术驱动的组织工程策略，以开发针对软组织移植物生物学固定的创新方法。具体而言，我们专注于肌腱到骨整合在肩袖修复和增强方面的挑战。肩袖撕裂是最常见的肩部受伤，在美国，每年进行75,000多次维修程序。我们的生物固定方法集中在肌腱和骨骼之间的解剖插入位点的再生上。鉴于细胞类型的特征空间变化，矩阵组成和天然插入位点固有的矿物含量，预计接口再生将需要多种细胞类型和一个分层的支架，能够支撑多组织形成。因此，我们已经开发了用于肌腱骨整合的仿生的，纳米纤维的双相支架，每个相都设计用于形成天然插入位点的非矿物化和矿化区域。该建议的目的是优化用于界面再生和多组织形成的多细胞培养和仿生脚手架设计参数。 AIM 1将检验以下假设：基于纳米纤维的支架上的成纤维细胞和成骨细胞反应将由纳米纤维的几何形状和矿物质含量控制。 AIM 2将集中于通过成纤维细胞和成骨细胞的共文化以及在体内的这些独特区域的维持中，形成了双相支架上非钙化和钙化组织区域的独特但连续区域。作为肩袖修复的一部分，我们为重新生成解剖纤维电界界面的努力代表了针对重大临床挑战的创新解决方案。此外，此处提出的基于纳米纤维的多相脚手架设计和共培养方法是高度原始的。预计拟议研究的成功完成将有助于开发新一代的综合固定装置，并证明纳米技术对工程复杂的肌肉骨骼组织系统的潜力，这些肌肉骨骼组织系统可以与人体无缝集成。肩袖肌腱移植物的生物固定对骨骼构成了重大临床挑战。该项目的重点是基于纳米纤维的脚手架的设计和优化，用于促进肌腱到骨的整合后袖口修复，重点是通过多个基于多型的caffold Design和成纤维细胞 - 稳定的copteo coplasts进行对成纤维细胞和成骨细胞分布的空间控制和成骨细胞的分布和多issue形成。由于全国和全球执行的大量肩袖修复程序，计划研究的结果将对公共卫生产生重大影响。此外，该项目可以通过彼此以及与宿主环境相互整合以及通过移植物的整合来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翻译中产生广泛的影响。

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.

• 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.