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.

项目概要 由于关节软骨的愈合能力有限，需要临床干预来预防 进一步的关节软骨损伤和退行性骨关节炎的早期发作。目前手术 手术导致修复不充分，与周围透明软骨融合不良 并形成纤维软骨而不是正常的透明软骨。最常用的修复方法 膝关节软骨小症状病变的治疗方法是微骨折，其中多个 在软骨下骨上打孔，使骨髓中的干细胞迁移到关节 表面并便于修复。但从长远来看，这种方法并不能取代 正常的透明软骨。这里描述的方法是将手术治疗结合起来 微断裂，这将为缺损部位提供能够软骨形成的内源性细胞， 新型支架在发育过程中模仿软骨细胞外基质，以促进 软骨发生和软骨组织形成。在软骨发育过程中，主要基质 成分是胶原蛋白和蛋白聚糖，其中主要的糖胺聚糖（GAG） 蛋白多糖是6-硫酸软骨素和硫酸肝素。硫酸化的模式和程度 这些和其他 GAG 在提供生长所需的功能/生物活性方面发挥着不可或缺的作用 软骨发育过程中因素的相互作用。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纤维素半合成衍生物，它是 最丰富的天然材料之一。纤维素硫酸钠 (NaCS) 是水溶性的， 模仿GAG的结构，将被制作成支架并与微断裂相结合作为 软骨修复的新策略。在我们迄今为止的研究中，完全硫酸化的 NaCS 在 促进软骨形成，加速骨软骨缺损的修复。我们假设 NaCS 将赋予与 GAG 类似的功能品质、直接软骨形成和软骨组织 形成。在拟议的补充中，将解决两个具体目标，以补充正在进行的 在家长补助金中学习。目标 1 将研究含 NaCS 的支架上的软骨形成和 体外支架整合。该目的的目的是评估软骨组织的形成和整合 软骨外植体模型中的周围宿主软骨。目标 2 将研究体外软骨形成 以及使用微流体装置在生理相关条件下进行支架整合。调查结果还将 进一步了解含有 NaCS 的支架修复软骨损伤的机制。