Hybrid Composite Scaffolds for Cartilage Tissue Engineering

描述(申请人提供)：骨关节炎形式的关节软骨损伤和随后的退化是全球主要的健康问题，目前的估计报告称，到2020年，超过5900万美国人将被诊断为关节炎。由于软骨损伤的治疗选择很少，而且成功的程度有限，晚期疾病需要全关节置换术。尽管已有成熟的治疗方法，但该手术的有限寿命使得这种治疗方法对于更年轻或更活跃的个体来说是不可接受的，因为每次关节置换的翻修都涉及到逐渐复杂的治疗。本研究的目标是开发一种由成人干细胞通过皮下脂肪吸脂获得的组织工程化关节置换，结合工程生物材料支架和新型生物诱导基质形成软骨组织来替代髋关节的整个表面。我们将把一种新的三维(3D)纤维编织技术与人类脂肪来源的成人干细胞和一种来自关节软骨的新型杂交生物基质相结合，创造出一层可用于完全修复受损关节表面的活软骨层。我们将使用一种3D编织支架，它几乎复制了最初细胞种植时关节软骨的承载力学性能，因此可以快速植入，而不需要延长体外培养时间或使用生物反应器。这项技术的主要进展是开发了一种来自同种异体关节软骨移植物理处理的软骨诱导剂；这种材料导致了ASCs在体外快速合成软骨大分子。这项研究的最终目标是开发能够应用于具有复杂生物力学特性的各种组织的功能组织工程的技术。作为第一步，我们将展示3D支架可以与软骨衍生基质结合形成纤维增强复合材料，并且细胞种植结构的生物和机械性能将与关节软骨在早期和晚期培养时的复杂力学性能相匹配。其次，我们将评估纤维增强支架在体外培养期间保持成型形状的能力，以表明定制我们的植入物以匹配体内复杂的轮廓和几何形状是可能的。生物力学功能水平的提高有望提高肌肉骨骼系统以及身体其他器官系统的各种组织的工程修复的成功水平。公共卫生相关性：这个第一阶段SBIR项目的目标是开发一种用于生物人工关节表面处理的新型混合技术，作为治疗髋关节骨性关节炎的方法。技术基础包括结合成人干细胞，通过吸脂从皮下脂肪中提取，并在纤维增强的支架中使用重组的天然组织细胞外基质来调节干细胞的生长和分化。这项研究的最终目标是开发最终可用于治疗骨关节炎和其他关节疾病的组织工程技术。

DESCRIPTION (provided by applicant): Damage and subsequent degeneration of articular cartilage in the form of osteoarthritis represents a major health issue globally, and current estimates report that by the year 2020, over 59 million Americans will be diagnosed with arthritis. As treatment options for the treatment of cartilage lesions are few in number and success is somewhat limited, advanced disease requires total joint replacement. Though well-established, the finite life span of the procedure makes this treatment unacceptable for younger or more active individuals as revisions involve progressively complicated treatment with each joint replacement. The goal of this study is to develop a tissue engineered joint replacement from adult stem cells, derived via liposuction from subcutaneous fat, in combination with an engineered biomaterial scaffold, and a novel bioinductive matrix to form cartilaginous tissue to replace the entire surface of the hip joint. We will combine a novel three-dimensional (3D) fiber weaving technology with human adipose derived adult stem cells and a novel hybrid biomatrix derived from articular cartilage to create a layer of living cartilage that can be used to completely replace a damaged joint surface. We will use a 3D woven scaffold that nearly replicates the load-bearing mechanical properties of articular cartilage at the time of initial cell seeding, thus allowing rapid implantation without a prolonged in vitro culture period or use of a bioreactor. The primary advance of this technology is the development of a chondrogenic inducing agent derived from physical processing of articular cartilage allograft; this material results in rapid synthesis of cartilage macromolecules by ASCs in vitro. The ultimate goal of this study is to develop technologies that can be applied to functional tissue engineering of a variety of tissues that possess complex biomechanical properties. As a first step, we will show that the 3D scaffold can be combined with the cartilage-derived matrix to form a fiber reinforced composite and that the biological and mechanical properties of the cell- seeded constructs will match the complex mechanical properties of articular cartilage both in early and late culture. Secondly, we will assess the ability of the fiber reinforced scaffold to maintain the molded shape over the in vitro culture period to show that it is possible to customize our implants to match complex in vivo contours and geometries. An improved level of biomechanical function will hopefully increase the level of success in the engineered repair of various tissues of the musculoskeletal system as well as other organ systems of the body. PUBLIC HEALTH RELEVANCE: The goal of this Phase I SBIR project is to develop a novel hybrid technology for bioartificial joint resurfacing as a treatment for hip osteoarthritis. The technologic basis involves a combination of adult stem cells, retrieved from subcutaneous fat via liposuction and the use of reconstituted native tissue extracellular matrix in a fiber-reinforced scaffold to regulate stem cell growth and differentiation. The ultimate goal of this study is to develop tissue engineering technologies that can eventually be used to treat osteoarthritis and other joint diseases.