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.

项目摘要 由于关节软骨的愈合能力有限，因此需要进行临床干预以防止 进一步的关节软骨损伤和退化性骨关节炎的早期发作。当前手术 程序导致维修不足，由于整合不良的透明软骨 并形成纤维网状，而不是正常的透明软骨。最常用的修复 膝盖关节软骨的小症状病变的治疗是微裂缝的，其中有多个 在软骨下骨中制成孔，使从骨髓中的干细胞迁移到关节 表面并促进修复。但是，从长远来看，此方法并不能替代 正常的透明软骨。这里描述的方法是结合手术治疗 微裂缝将提供能够为缺陷部位提供软骨发生的内源细胞， 在开发过程中模仿软骨细胞外基质的新型脚手架以促进 软骨发生和软骨组织形成。在软骨开发过程中，主要矩阵 成分是胶原蛋白和蛋白聚糖，其中主要的糖胺聚糖（gags） 蛋白聚糖是软骨素-6-硫酸盐和硫酸肝素。硫酸的模式和程度 这些和其他插科打在提供增长的必要功能/生物活性方面起着不可或缺的作用 软骨发育中的因子相互作用。典型的合成生物材料缺乏功能位点 启用这种互动。这项研究将研究一种新型的半合成衍生物，纤维素是 最丰富的天然材料之一。硫酸钠硫酸钠（NACS），水溶性和 模拟插科打术的结构将被制成脚手架，并与微裂缝结合为 软骨修复的新型策略。在我们迄今为止的研究中，完全硫化的NACS在 促进软骨发生并加速骨软骨缺损的修复。我们假设这一点 NACS将赋予类似于插科打的功能质量，直接软骨发生和软骨组织 形成。在拟议的补充剂中，将解决两个具体目标，以补充正在进行的 在父母赠款中进行研究。 AIM 1将研究针对含NACS的支架的软骨发生和 体外脚手架整合。此目的的目的是评估软骨组织的形成和整合 在软骨外植体模型中带有周围的主机软骨。 AIM 2将研究体外软骨发生 使用微流体设备在生理上与生理相关的条件下的脚手架整合。调查结果也将 在修复软骨病变时，提供对含有支架的NAC的进一步机械理解。