Bioengineering Annulus Fibrosus using Silk Scaffold

使用丝支架的生物工程纤维环

• 批准号: 6960648
• 负责人: RITA A KANDEL
• 金额: $ 13.07万
• 依托单位: SINAI HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6960648
• 关键词: SDS polyacrylamide gel electrophoresis; autoradiography; biodegradable product; bioengineering /biomedical engineering; biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; bioreactors; biotechnology; intervertebral disk; polymerase chain reaction; regeneration; spine disorder; tissue support frame

DESCRIPTION (provided by applicant): Degenerative intervertebral disc disease is a very common problem and currently there is no optimal treatment for individuals who develop persistent back disease as a result of this disease. Although back pain is rarely life-threatening, the annual cost in terms of lost productivity, medical expenses and workers' compensation benefits was estimated at $50 billion in 1998 in the United States. The long term goal of our research is to generate using a bioengineering approach a spinal unit in vitro that has tissue, which structurally and functionally approaches that of a natural intervertebral disc and is suitable as replacement for a damaged disc. Additionally this model can be used to investigate mechanisms regulating disc tissue formation, maintenance, and degeneration in vitro to identify new ways to regenerate disc tissue or new therapeutic agents to treat or prevent the disease. Our immediate aim is to develop a model of a spinal unit consisting of intervertebral disc tissue and cartilage endplate formed on and anchored into a porous bone substitute material. The specific aims of this proposal are: 1) To design a porous biodegradable polymeric scaffold made of silk with an organization to allow guided tissue formation to mimic the in vivo annulus fibrosus organization. 2) To form annulus fibrosus tissue in vitro, utilizing the silk scaffold. Annulus fibrosus cells will be seeded into the scaffold. The cells will be allowed to form tissue in a bioreactor in the presence or absence of a mechanical force (compression and/or shear). An optimal loading regime defined by amplitude and duration offeree application will be determined and the effect of this in vitro mechanical stimulation on tissue composition, collagen organization, and mechanical properties will be determined. 3) To generate a model of portion of a spinal unit composed of in vitro-formed annulus fibrosus tissue surrounding the nucleus pulposus, cartilage integrated with the top surface of a bone substitute (calcium polyphosphate). The viability and mechanical properties of the tissue will be evaluated.

描述（由申请人提供）：退化性椎间盘疾病是一个非常普遍的问题，目前尚无最佳治疗方法，对于由于这种疾病而发展持续性背部疾病的个体。尽管背部疼痛很少威胁生命，但在1998年，估计生产力，医疗费用和工人的薪酬福利损失的年成本估计为500亿美元。我们研究的长期目标是在体外使用生物工程方法生成具有组织的脊柱单元，该方法在结构和功能上接近天然椎间盘的脊柱，并适合替换损坏的椎间盘。此外，该模型可用于调查调节盘状组织形成，维持和变性的机制，以识别新的方法来再生椎间盘组织或新的治疗剂以治疗或预防疾病。我们的直接目的是开发由椎间盘组织和软骨终板组成的脊柱单元的模型，并锚定在多孔骨替代物质中。该提案的具体目的是：1）设计由丝绸与组织制成的多孔生物降解的聚合物支架，以允许指导组织形成以模仿体内纤维纤维组织。 2）利用丝绸支架，在体外形成纤维纤维组织。纤维纤维细胞将被接种到支架中。在存在或不存在机械力（压缩和/或剪切）的情况下，将允许细胞在生物反应器中形成组织。将确定由幅度和持续时间施加量的最佳负载状态，并确定该体外机械刺激对组织组成，胶原蛋白组织和机械性能的影响。 3）生成由底细胞核周围的体外形成的纤维组织组织组成的脊柱单位的模型，该模型与骨替代的顶部表面（钙磷酸钙）集成了软骨。将评估组织的生存力和机械性能。