Engineering Spatiotemporal Osteochondral Tissue Formation with Tunable 3D-Printed Scaffolds

使用可调谐 3D 打印支架工程设计时空骨软骨组织形成

• 批准号: 10373762
• 负责人: Lesley W Chow
• 金额: $ 16.69万
• 依托单位: LEHIGH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373762
• 关键词: 3D Print; Address; Adult; Affect; Age; American; BMP2 gene; Biochemical; Biocompatible Materials; Bone Marrow; Cartilage; Cartilage injury; Cell Culture Techniques; Cells; Chemistry; Chondrocytes; Chondrogenesis; Clinical; Clinical Engineering; Cues; Defect; Degenerative polyarthritis; Deposition; Development; Disease; Early treatment; Economic Burden; Engineering; Event; Fibrocartilages; Growth Factor; Healthcare Systems; Human; Implant; In Situ; In Vitro; Inferior; Ink; Intervention; Joints; Knowledge; Life; Location; Mechanics; Medicare; Medicine; Mesenchymal Stem Cells; Natural regeneration; Operative Surgical Procedures; Orthopedics; Osteoblasts; Osteogenesis; Outcome; Pain; Pathology; Patients; Peptides; Polymers; Proteins; Quality of life; Replacement Arthroplasty; Research; Resolution; Surface; Techniques; Testing; Therapeutic; Time; Tissue Engineering; Tissue constructs; Tissues; Transforming Growth Factors; United States; Work; adult stem cell; articular cartilage; base; biodegradable scaffold; bone; cartilage development; cartilage regeneration; cartilage repair; clinically relevant; debilitating pain; design; drug discovery; functional outcomes; human old age (65+); improved; in vitro Model; innovation; joint destruction; joint function; osteochondral tissue; osteogenic; patient mobility; peptidomimetics; prevent; programs; repaired; replacement tissue; response; scaffold; spatiotemporal; stem cell differentiation; stem cells; success

PROJECT SUMMARY Osteoarthritis is a degenerative joint disease that affects 70% of adults over age 65, but the initial cartilage injury usually occurs much earlier in life. Progressive joint degeneration during adulthood continues because cartilage has very limited ability to self-repair. Current surgical interventions to repair cartilage defects at early stages result in low quality tissue with limited long-term success. The new tissue degrades over time, which increases exposure of the underlying bone and leads to debilitating pain. Many patients ultimately seek relief through total joint replacement to regain mobility and improve quality of life. However, over half of all joint replacement patients in the United States are under age 65. These younger patients are expected to outlive their implants and may require one or more revision surgeries over their lifetime. This places a significant burden on the healthcare system, especially the Medicare program. The objective of this project is to develop a promising biomaterials-based approach that addresses a persistent challenge in orthopaedic medicine—the need for long-lasting treatments for early-stage cartilage defects. This work involves an innovative combination of 3D printing and biomaterials design to fabricate biodegradable scaffolds for functional cartilage repair. To achieve this, the scaffolds are engineered to guide regeneration of the entire osteochondral tissue to improve bone-cartilage integration and durability. Scaffolds will be fabricated by 3D printing polymer-based “inks” that include special chemistries to localize specific biochemical cues called peptides. These peptides can be designed to direct formation of bone or cartilage tissue. The inks will be spatially deposited using 3D printing to create distinct bone-promoting and cartilage-promoting regions within a continuous construct. Notably, the bioactive peptides can be introduced over time to mimic compositional changes that occur during articular cartilage development. The proposed research plan includes two specific aims designed to study how human mesenchymal stem cells (adult stem cells found in bone marrow) respond to scaffolds presenting bone-promoting and cartilage-promoting peptides. We hypothesize that spatially presenting these peptides over time to mimic events that occur during development will promote stable osteochondral tissue formation. The first aim will investigate how modifying the presentation of these peptides over time in the presence of stem cells influences their differentiation, or transition, into bone-like or cartilage-like states. The second aim will examine how spatially presenting both peptides in the same scaffold guides local stem cell differentiation into bone-like and cartilage-like tissue regions. The proposed approach is powerful because it exploits high-resolution 3D printing to produce scaffolds with highly tunable compositions designed to direct osteochondral interface regeneration. This is a key requirement for long-term functional cartilage repair. This work will lead to breakthroughs in the ability to engineer clinically relevant tissue replacements that prevent the onset or debilitating progression of osteoarthritis.

项目摘要 骨关节炎是一种退化性关节疾病，影响65岁以上的成年人的70％，但最初的软骨损伤 通常发生在生活中要早得多。在成年期间进行性关节变性，因为软骨 自我修复的能力非常有限。当前的手术干预措施以修复早期的软骨缺陷 导致低质量组织的长期成功。随着时间的推移，新的组织会降解，这会增加 暴露于潜在的骨骼并导致使人衰弱的疼痛。许多患者最终通过总共寻求缓解 关节替代者保持流动性并改善生活质量。但是，超过一半的关节替代患者 在美国，年龄在65岁以下。预计这些年轻患者将超过其乱七八期，可能 一生中需要一项或多项修订手术。这对医疗保健有重大燃烧 系统，尤其是Medicare计划。 该项目的目的是开发一种有前途的基于生物材料的方法，以解决持续 骨科医学中的挑战 - 对早期软骨缺陷的长期治疗的需求。这 工作涉及3D打印和生物材料设计的创新组合以制造可生物降解 功能性软骨修复的脚手架。为了实现这一目标，脚手架经过设计以指导 整个骨软骨组织，以改善骨 - 骨折的整合和耐用性。脚手架将被捏造 通过3D打印聚合物的“墨水”，其中包括特殊化学物质，以定位特定的生化提示称为 肽。这些肽可以设计用于导致骨或软骨组织的形成。墨水将在空间上 使用3D打印沉积以在一个内部创建独特的骨骼和软骨促进区域 连续结构。值得注意的是，随着时间的推移，生物活性宠物可以引入模拟成分 关节软骨发育过程中发生的变化。 拟议的研究计划包括两个特定目的，旨在研究人类间充质干细胞的方式 （在骨髓中发现的成年干细胞）对表现出骨骼和软骨促进的支架的反应 肽。我们假设随着时间的流逝，它们在空间上表现为模仿在 发育将促进稳定的骨软骨组织形成。第一个目标将调查如何修改 在存在干细胞的情况下，这些肽随着时间的推移呈现会影响其分化或过渡 进入骨状或软骨状状态。第二个目的将研究如何在空间上呈现两个宠物 相同的脚手架指导局部干细胞分化为骨状和软骨状组织区域。提议 方法是强大的，因为它利用高分辨率3D打印来产生高度可调的脚手架 旨在引导骨软骨界面再生的组成。这是长期的关键要求 功能软骨修复。这项工作将导致设计与临床相关组织的能力突破 替代骨关节炎的发作或使人衰弱的进展。