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 股骨头坏死（ONFH）是一种潜在的衰弱性疾病，发病率正在上升 国际吧仅在美国，每年诊断出约20，000例ONFH病例。高达 在美国，18%的全髋关节置换术（THR）是ONFH的结果。在ONFH的早期阶段， 已经尝试了各种保留髋关节的药物和手术治疗，但成功有限。这是由于 维持患者自身股骨头需要机械和生物策略 以承受间歇性载荷，同时重建坏死的股骨头段。我们 长期目标是使用组织工程方法改善ONFH的治疗。我们的整体 一种假设是，仿生功能分级支架（FGS）和预处理或 具有抗炎、成骨和血管生成作用的基因修饰（GM）间充质干细胞（MSC） 促进信号将提供增强的机械和生物学线索以重建骨坏死 在ONFH的部分。为了验证这些假设，我们建立了具有骨科手术专业知识的团队， 生物材料和组织工程提出了以下具体目标：目标1是建立 FGS用于激素诱导的ONFH的股骨头重建。目的2是确定以下上级疗效： 与未修饰的MSC相比，增强的、预处理的或GM MSC用于在骨中重建骨， 激素诱导的股骨头坏死。目的3是证实FGS和增强的组合 MSC比治疗或治疗更大程度地优化了ONFH的机械和生物学特性 单独进行核心减压这一直接翻译项目将彻底改变和显着改善 通过引入两种新的连续疗法治疗ONFH， 与预处理或GM MSC一起用于股骨头重建和保存。 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