A Novel Glycosaminoglycan Mimetic Scaffold for Cartilage Repair - diversity supplement

用于软骨修复的新型糖胺聚糖模拟支架 - 多样性补充

• 批准号: 10406732
• 负责人: Treena Lynne Arinzeh
• 金额: $ 6.54万
• 依托单位: NEW JERSEY INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406732
• 关键词: Address; Adult; Affect; American; Biocompatible Materials; Bone Marrow Stem Cell; CSPG6 gene; Cartilage; Cells; Cellulose; Chondrogenesis; Clinical; Collagen; Complement; Defect; Degenerative polyarthritis; Development; Extracellular Matrix; Fibrocartilages; Glycosaminoglycans; Goals; Growth Factor Interaction; Heparin; Hyaline Cartilage; In Vitro; Intervention; Joints; Knee; Lesion; Methods; Microfluidic Microchips; Modeling; Operative Surgical Procedures; Pattern; Physiological; Play; Proteoglycan; Role; Site; Sodium; Structure; Sulfate; Surface; Tissues; Water; articular cartilage; cartilage development; cartilage repair; cellulose sulfate; early onset; healing; mimetics; novel; novel strategies; osteochondral repair; parent grant; prevent; repaired; scaffold; subchondral bone

Project Summary With the limited healing capability of articular cartilage, clinical intervention is necessary to prevent further articular cartilage damage and early onset of degenerative osteoarthritis. Current surgical procedures result in inadequate repair suffering from poor integration with surrounding hyaline cartilage and the formation of fibrocartilage instead of normal hyaline cartilage. The most frequently used reparative treatment for small symptomatic lesions of articular cartilage of the knee is microfracturing, where multiple holes are made in the subchondral bone allowing stem cells from the bone marrow to migrate to the joint surface and facilitate repair. However, in the long-term, this method does not result in the replacement of normal hyaline cartilage. The approach described here is to combine the surgical treatment of microfracturing, which will provide endogenous cells capable of chondrogenesis to the defect site, with a novel scaffold that mimics the cartilage extracellular matrix during development to promote chondrogenesis and cartilage tissue formation. During cartilage development, the major matrix components are collagens and proteoglycans, wherein the predominant glycosaminoglycans (GAGs) in the proteoglycans are chondroitin-6-sulfate and heparin sulfate. The pattern and degree of sulfation in these and other GAGs play an integral role in providing the necessary functionality/bioactivity for growth factor interactions in cartilage development. Typical synthetic biomaterials lack functional sites that would enable this interaction. This study will investigate a novel, semi-synthetic derivative of cellulose, which is one of the most abundant natural materials. Sodium cellulose sulfate (NaCS), which is water soluble and mimics the structure of GAG, will be fabricated into a scaffold and combined with microfracturing as a novel strategy for cartilage repair. In our studies to date, fully sulfated NaCS has shown promise in promoting chondrogenesis and accelerating the repair of osteochondral defects. We hypothesize that NaCS will impart functional qualities that are similar to GAGs, direct chondrogenesis and cartilage tissue formation. In the proposed supplement, two specific aims will be addressed that complement the ongoing studies in the parent grant. Aim 1 will Investigate chondrogenesis on NaCS-containing scaffolds and scaffold integration in vitro. The goal of this aim is to evaluate cartilage tissue formation and integration with surrounding host cartilage in a cartilage explant model. Aim 2 will investigate in vitro chondrogenesis and scaffold integration in physiologically-relevant conditions using a microfluidic device. Findings will also provide further mechanistic understanding of the NaCS containing scaffolds in repairing cartilage lesions.

项目总结