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，临床干预是必要的。 进一步的关节软骨损伤和退行性骨关节炎的早期发病。当前外科手术 手术导致修复不充分，与周围透明软骨整合不良 纤维软骨的形成取代了正常的透明软骨。最常用的修复剂 膝关节软骨小症状性病变的治疗是微骨折，其中多发性 软骨下骨上会打洞，让骨髓中的干细胞迁移到关节上。 表面平整，便于维修。然而，从长远来看，这种方法并不会导致 正常的透明软骨。这里所描述的方法是结合手术治疗 微骨折，这将提供内源性细胞能够向缺损处形成软骨，具有 新型支架在发育过程中模拟软骨细胞外基质促进 软骨生成和软骨组织形成。在软骨发育过程中，主要基质 成分是胶原蛋白和蛋白多糖，其中主要的糖胺聚糖(GAG)在 蛋白多糖是软骨素-6-硫酸盐和硫酸肝素。硫酸盐化的方式和程度 这些GAG和其他GAG在为生长提供必要的功能/生物活性方面发挥着不可或缺的作用 软骨发育中的因素相互作用。典型的合成生物材料缺乏功能位点， 启用此交互。这项研究将研究一种新型的半合成纤维素衍生物，它是 最丰富的天然材料之一。纤维素硫酸钠(NaCS)，可溶于水和 模拟GAG的结构，将被组装成支架并与微压裂相结合作为 软骨修复的新策略。在我们到目前为止的研究中，完全硫酸盐化的NAC在 促进软骨生成，加速骨软骨缺损修复。我们假设 NAC将提供类似于GAG、直接软骨生成和软骨组织的功能特性 队形。在拟议的补编中，将阐述两个具体目标，以补充正在进行的 父母助学金中的学习。AIM 1将研究含有NaCS的支架上的软骨生成和 支架体外整合。这个目标是评估软骨组织的形成和整合。 在软骨移植模型中与周围的宿主软骨。AIM 2将研究体外软骨形成 以及使用微流控装置在生理相关条件下整合支架。调查结果还将 提供对含有支架的NaCS修复软骨损伤的进一步的机制理解。