Hybrid Composite Scaffolds for Cartilage Tissue Engineering

描述（由申请人提供）：骨关节炎形式的关节软骨的损伤和随后的退化代表了全球的主要健康问题，并且目前的估计报告称，到2020年，超过5900万美国人将被诊断患有关节炎。由于治疗软骨病变的治疗选择很少，成功率也有限，晚期疾病需要全关节置换。虽然已得到公认，但手术的有限寿命使得这种治疗对于年轻或更活跃的个体是不可接受的，因为翻修涉及每次关节置换的逐渐复杂的治疗。本研究的目的是开发一种组织工程关节置换术，该关节置换术由成人干细胞通过皮下脂肪吸脂获得，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，以取代髋关节的整个表面。我们将结合联合收割机一种新的三维（3D）纤维编织技术与人类脂肪来源的成体干细胞和一种新的混合生物基质来源于关节软骨，以创造一层活软骨，可用于完全取代受损的关节表面。我们将使用一种3D编织支架，该支架几乎复制了最初细胞接种时关节软骨的承重机械性能，从而允许快速植入，而无需延长体外培养期或使用生物反应器。该技术的主要进展是开发了一种软骨诱导剂，其来源于关节软骨同种异体移植物的物理处理;该材料导致体外ASC快速合成软骨大分子。本研究的最终目标是开发可应用于具有复杂生物力学特性的各种组织的功能性组织工程的技术。作为第一步，我们将展示3D支架可以与软骨衍生基质组合以形成纤维增强复合材料，并且细胞接种构建体的生物学和机械性质将在早期和晚期培养中匹配关节软骨的复杂机械性质。其次，我们将评估纤维增强支架在体外培养期间保持模制形状的能力，以表明可以定制我们的植入物以匹配复杂的体内轮廓和几何形状。生物力学功能水平的提高将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：该一期SBIR项目的目标是开发一种新的混合技术，用于生物人工关节表面置换，作为髋关节骨关节炎的治疗。技术基础涉及通过抽脂从皮下脂肪中提取的成体干细胞的组合，以及在纤维增强支架中使用重建的天然组织细胞外基质来调节干细胞生长和分化。这项研究的最终目标是开发组织工程技术，最终可用于治疗骨关节炎和其他关节疾病。

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.