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: 10629168
• 负责人: Lesley W Chow
• 金额: $ 19.25万
• 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 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629168
• 关键词: 3D Print; Address; Adult; Affect; Age; American; BMP2 gene; Binding; 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; 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; Reaction; Repeat Surgery; Replacement Arthroplasty; Research; Resolution; Second Look Surgery; Surface; Techniques; Testing; Therapeutic; Time; Tissue Engineering; Tissue constructs; Tissues; Transforming Growth Factor beta; Transforming Growth Factors; United States; Work; adult stem cell; articular cartilage; biodegradable scaffold; bone; cartilage development; cartilage regeneration; cartilage repair; clinically relevant; debilitating pain; design; drug discovery; functional improvement; human old age (65+); improved; in vitro Model; innovation; joint destruction; joint function; knowledge integration; 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.

项目总结