Tissue Engineering Approaches for Improved Treatment of Early Stage Osteonecrosis of the Hip

改善早期髋骨坏死治疗的组织工程方法

• 批准号: 10394866
• 负责人: STUART B GOODMAN
• 金额: $ 42.65万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-05 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394866
• 关键词: 3D Print; Affect; Age-Years; Anti-Inflammatory Agents; Area; Arthritis; Biocompatible Materials; Biological; Biomimetics; Blood Vessels; Bone Marrow; Bone Regeneration; Bone necrosis; Bone remodeling; Cartilage; Cell Death; Cell Therapy; Cues; Degenerative polyarthritis; Diagnosis; Disease; Disease Progression; Distal; Early Intervention; Early treatment; Engineering; Etiology; Femur; Genetic Engineering; Goals; Head; Hip Joint; Hip region structure; Implant; Incidence; Individual; Interleukin-4; Joints; Lead; Maintenance; Mechanics; Medical; Mesenchymal Stem Cells; Nature; Necrosis; Operative Surgical Procedures; Orthopedic Surgery; Oryctolagus cuniculus; Osseointegration; Osteogenesis; Pain; Patients; Porosity; Progressive Disease; Property; Race; Signal Transduction; Steroids; Testing; Therapeutic Effect; Time; Tissue Engineering; Total Hip Replacement; United States; Up-Regulation; Weight-Bearing state; articular cartilage; bone; bone healing; caprolactone; cytokine; density; design; implantation; improved; mechanical load; mechanical properties; novel; novel strategies; osteogenic; preconditioning; preservation; prevent; reconstitution; regenerative; repaired; scaffold; stem cell therapy; success; tricalcium phosphate

Project Abstract Osteonecrosis of the femoral head (ONFH) is a potentially debilitating disease that is increasing in incidence worldwide. In the United States alone, approximately 20,000 cases of ONFH are diagnosed each year. Up to 18% of total hip replacements (THR) performed in the USA are a result of ONFH. In the early stages of ONFH, various hip joint preserving medical and surgical treatments have been tried with limited success. This is due to the fact that maintenance of the patient's own femoral head requires both mechanical and biological strategies to withstand intermittent loading and, at the same time, reconstitute the necrotic femoral head segment. Our long-term goal is to improve the treatment of ONFH using a tissue engineering approach. Our overall hypothesis is that the combination of a biomimetic functionally-graded scaffold (FGS), and preconditioned or genetically modified (GM) mesenchymal stem cells (MSCs) with anti-inflammatory, osteogenic and vascular promoting signals will provide enhanced mechanical and biological cues to reconstitute the osteonecrotic segment in ONFH. To test these hypotheses, our established team with expertise in orthopaedic surgery, biomaterials, and tissue engineering proposes the following Specific Aims: Aim 1 is to establish the efficacy of FGS for reconstitution of the femoral head in steroid-induced ONFH. Aim 2 is to establish superior efficacy of enhanced, preconditioned or GM MSCs, compared to unmodified MSCs for reconstitution of bone in the femoral head in steroid-induced ONFH. Aim 3 is to confirm that the combination of the FGS and enhanced MSCs optimizes the mechanical and biological properties in ONFH to a greater degree than either treatment or core decompression alone. This directly translational project will revolutionize and significantly improve the treatment of ONFH by introducing two novel adjunctive therapies consisting of a biomimetic resorbable load- bearing implant together with preconditioned or GM MSCs for femoral head reconstitution and preservation. 1" "

项目摘要 股骨头（ONFH）的骨坏死是一种潜在的使人衰弱的疾病，发生率正在增加 全世界。仅在美国，每年就会诊断出约20,000例ONFH病例。到 在美国执行的总髋关节置换量（THR）的18％是ONFH的结果。在ONFH的早期阶段， 已经尝试了各种髋关节保存医学和手术治疗的方法，取得了有限的成功。这是由于 维持患者自己的股骨头需要机械和生物学策略的事实 为了承受间歇性的负载，并同时重建坏死的股骨头部。我们的 长期目标是使用组织工程方法改善ONFH的处理。我们的整体 假设是仿生型功能分级支架（FGS）和预处理或 具有抗炎，成骨和血管的转基因（GM）间充质干细胞（MSC） 促进信号将提供增强的机械和生物学提示，以重建骨质生物 onfh中的细分。为了检验这些假设，我们成熟的团队具有骨科手术专业知识， 生物材料和组织工程提出以下特定目的：目标1是确定 用于在类固醇引起的ONFH中重建股头的FGS。目标2是建立卓越的功效 与未修改的MSC相比，增强，预处理或GM MSC是重新建立的MSC 类固醇引起的股骨头。 AIM 3是确认FG和增强的组合 MSC比治疗或以下方面优化ONFH中的机械和生物学特性 仅核心减压。这个直接的转化项目将彻底改变并显着改善 通过引入两种新型辅助疗法来治疗ONFH 轴承植入物以及用于股骨头重建和保存的预处理或GM MSC。 1“ “

项目成果

CORR Insights®: CORR® ORS Richard A. Brand Award: Disruption in Peroxisome Proliferator-Activated Receptor- γ (PPARG) Increases Osteonecrosis Risk Through Genetic Variance and Pharmacologic Modulation.

CORR Insights®：CORR® ORS Richard A. 品牌奖：过氧化物酶体增殖物激活受体-γ (PPARG) 的破坏通过遗传变异和药理学调节增加骨坏死风险。

• DOI: 10.1097/corr.0000000000000789
• 发表时间: 2019
• 期刊: Clinical orthopaedics and related research
• 影响因子: 4.2
• 作者: Goodman,StuartB

NFκB sensing IL-4 secreting mesenchymal stem cells mitigate the proinflammatory response of macrophages exposed to polyethylene wear particles.

• DOI: 10.1002/jbm.a.36504
• 发表时间: 2018-10
• 期刊: Journal of biomedical materials research. Part A
• 作者: Lin T;Kohno Y;Huang JF;Romero-Lopez M;Pajarinen J;Maruyama M;Nathan K;Yao Z;Goodman SB
• 通讯作者: Goodman SB

Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model.

• DOI: 10.1186/s13287-023-03260-4
• 发表时间: 2023-04-21
• 期刊: Stem cell research & therapy
• 影响因子: 7.5

Recent advances in 3D bioprinting of musculoskeletal tissues.

• DOI: 10.1088/1758-5090/abc8de
• 发表时间: 2021-03-10
• 期刊: Biofabrication
• 影响因子: 9
• 作者: Potyondy T;Uquillas JA;Tebon PJ;Byambaa B;Hasan A;Tavafoghi M;Mary H;Aninwene GE 2nd;Pountos I;Khademhosseini A;Ashammakhi N
• 通讯作者: Ashammakhi N

Tumor necrosis factor primes and metal particles activate the NLRP3 inflammasome in human primary macrophages.

• DOI: 10.1016/j.actbio.2020.03.017
• 发表时间: 2020-05
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Jämsen E;Pajarinen J;Kouri VP;Rahikkala A;Goodman SB;Manninen M;Nordström DC;Eklund KK;Nurmi K
• 通讯作者: Nurmi K