Chondroitin sulfate-fiber hydrogels for cartilage tissue engineering

描述（由申请方提供）：在日常活动期间，类关节的透明软骨承受显著负荷和重复循环。由于高负荷和损伤的创伤，可以形成软骨损伤，并可能导致骨关节炎（OA）。这些软骨损伤的普遍性和软骨有限的修复能力导致了对开发修复软骨损伤的新材料和方法的广泛研究。我们的实验室专注于使用生物材料和细胞进行手术干预，以修复软骨病变。本研究的目的是开发纤维状水凝胶用于软骨病变的组织工程。水凝胶和静电纺丝纤维支架作为软骨组织工程的材料已经进行了广泛的研究。然而，这些材料还没有被研究在共轭彼此。通过将电纺网片并入水凝胶中，我们将能够模拟天然软骨的蛋白聚糖凝胶和胶原纤维。我们假设，通过将由硫酸软骨素（CS）制成的纤维网片掺入我们目前感兴趣的水凝胶聚乙二醇（PEG）中，我们可以使用软骨细胞和软骨分化间充质干细胞实现增强的软骨样组织形成。我们建议使用硫酸软骨素作为电纺纳米纤维的基础材料，因为我们实验室以前的研究表明，与PEG水凝胶相比，在CS水凝胶和纤维水凝胶形式存在下，间充质干细胞的软骨形成增强。除了增强形成的软骨组织，我们相信这些纤维还将在组织修复和整合过程中为支架提供显著的机械稳定性。为了实现这一目标，我们将首先电纺硫酸软骨素为基础的纳米纤维和评估软骨样组织的形成。这将由1执行。）将细胞直接接种到电纺纤维上，和2.）将纤维网掺入PEG水凝胶中，随后分析形成的组织。将使用皮下植入随后植入大鼠髁状突缺损中来验证所开发的纤维水凝胶的体内翻译。相关性：大约65%的60岁以上老年人患有骨关节炎（OA），导致疼痛和可能的行动不便。目前的OA治疗受到组织修复不足的限制，通常需要进一步治疗。因此，有必要设计新的外科干预措施，以加强目前的治疗与生物材料的使用。

DESCRIPTION (provided by applicant): Hyaline cartilage of the diarthroidal joints undergoes significant loading and repetitive cycling during regular daily activity. Due to high loading and trauma from injury, cartilage lesions can form and may lead to osteoarthritis (OA). The prevalence of these cartilage lesions and the limited repair capabilities of cartilage has lead to extensive research in development of new materials and methods of repairing cartilage lesions. Our lab focuses on the use of biomaterials and cells to for surgical interventions to repair cartilage lesions. The objective of this project is to develop fibrous hydrogels for tissue engineering of cartilage lesions. Extensive research has been performed using hydrogels and electrospun fibrous scaffolds independently as materials for cartilage tissue engineering. However, these materials have not been studied in conjugation with each other. By incorporating electrospun meshes into hydrogels we will be able to mimic the proteoglycan gel and collagen fibers of native cartilage. We hypothesize that by incorporating fibrous meshes, made from chondroitin sulfate (CS), into our current hydrogel of interest, poly(ethylene glycol) (PEG), we win achieve enhanced cartilage-like tissue formation using chondrocytes and chondrogenically differentiating mesenchymal stem cells. We are proposing to use chondroitin sulfate as the base material for the electrospun nanofibers because previous research in our lab has shown enhanced chondrogenesis of mesenchymal stem cells in the presence of CS in the form of hydrogels and fiber-hydrogels compared to PEG hydrogels. In addition to enhancing the cartilage tissue formed we believe that these fibers will also lend significant mechanical stability to the scaffold during the process of tissue repair and integration. To achieve this objective we will first electrospin chondroitin sulfate-based nanofibers and evaluate the cartilage-like tissue formation. This will be performed by 1.) seeding the cells directly onto the electrospun fibers and 2.) incorporated the fiber meshes into PEG hydrogels followed by subsequent analysis of the tissue formed. In vivo translation of the developed fibrous hydrogels will be validated using subcultaneous implantation followed by implantations into condyle defects in rats. Relevance: Approximately 65% of those over the age of 60 years old are affected by osteoarthritis (OA) resulting in pain and possible immobility. The current treatments for OA are limited by inadequate tissue repair and typically result in the need for further treatments. Therefore, it is necessary to design new surgical interventions to enhance the current treatments with the use of biomaterials.