Design of polymers and bioreactors in the development of a tissue engineering strategy for degenerative disc disease

在拟议计划中解决的主要挑战是设计，合成和测试新的聚合物生物材料和生物反应器，用于开发退行性椎间盘疾病的新治疗方法。椎间盘是脊柱椎骨之间的结缔组织。它将椎骨固定在一起，吸收压缩载荷，并允许脊柱旋转、弯曲和扭转。椎间盘退变是40岁以上人群慢性疼痛和生活质量下降的常见原因。在北美，每年约有1200万患者被诊断患有这种疾病。治疗通常是姑息性的;然而，在这些患者中，约10%的患者最终需要手术。目前的手术方法提供了暂时的缓解，并且不能修复受损的椎间盘。提出了一种治疗方法，该方法包括去除变性组织，并用在聚合物生物材料内递送的再生细胞替代变性组织，该聚合物生物材料可以形成细胞支持性储库，同时为受损的椎间盘提供机械支持。再生细胞将最终产生替代组织，而同时聚合物生物材料降解。再生细胞将从脂肪中分离的干细胞中获得。这些干细胞将在基于椎间盘的细胞和组织生物学设计的生物反应器中被诱导成为椎间盘中心的典型细胞（髓核细胞）。用于递送细胞的聚合物生物材料将被设计为支持和证实转化的干细胞转化为髓核细胞，同时最终降解为生物相容性和容易从体内消除的产物。

The major challenge addressed in the proposed program is the design, synthesis, and testing of new polymeric biomaterials and bioreactors to be used for the development of a new treatment for degenerative intervertebral disc disease. The intervertebral disc is the connective tissue between the vertebral bones of the spine. It holds the verterbrae together, absorbs compressive loads, and allows the spine to rotate, bend, and twist. Degeneration of the intervertebral disc is a common source of chronic pain and reduced quality of life in people over the age of 40. About 12 million patients are diagnosed with this condition annually in North America. Treatment is typically palliative; however, in ~ 10% of these patients, surgery is ultimately necessary. Current surgical methods provide temporary relief, and do not repair the damaged disc. A treatment methodology is proposed that involves removing the degenerating tissue, and replacing it with regenerative cells delivered within a polymer biomaterial that can form a cell supportive depot while providing mechanical support to the damaged disc. The regenerative cells will ultimately produce replacement tissue while at the same time the polymer biomaterial degrades. The regenerative cells will be obtained from stem cells isolated from fat. These stem cells will be induced to become cells typical of the centre of the intervertebral disc (nucleus pulposus cells) in a bioreactor for this purpose designed based on the cell and tissue biology of the disc. The polymer biomaterials used to deliver the cells will be designed to support and substantiate the transformed stem cells into nucleus pulposus cells while ultimately degrading into products that are biocompatible and readily eliminated from the body.