TISSUE ENGINEERING OF SKELETAL MUSCLE

描述(由申请人提供)： 骨骼肌的结构缺陷从相对良性到严重衰弱不等。这种组织的畸形可能是发育异常或创伤性损伤的结果。无论来源如何，骨骼肌的结构性缺陷都会在许多不同的层面上影响患者。例如，面部肌肉系统的结构性缺陷可能会对患者的生存能力产生轻微影响。然而，即使是一个微小的外表缺陷也可能产生深远的心理影响。中枢性骨骼的肌肉缺陷会限制活动能力，从而降低生活质量。一个被忽视的颅面修复领域是组织工程骨骼肌假体领域。这项提议的目标是设计一种生物植入物，可以用来恢复功能失调的骨骼肌的结构和功能。理想情况下，这样的假体应该由骨骼肌肌管组成，排列成与完整肌肉相同的模式。工程组织应该是可塑性的，这样就可以雕刻组织来恢复缺失或受损肌肉的轮廓。在这项提案的初步数据部分，我们提出的证据表明，我们已经成功地构建了来源于新生儿卫星细胞的骨骼肌细胞的多层培养，呈现出三维的组织样模式。我们建议在这些初步实验的基础上开发一种预先适应体内环境并适合于移植和修复骨骼肌缺陷的三维骨骼肌结构。 这项建议的具体目标是： 1)。生产模仿成人骨骼肌结构和功能的骨骼肌结构，并预先适应体内环境。 2)。利用形态、生化、分子和生理学技术，以完整的组织为参照，表征工程化的三维骨骼肌结构。

DESCRIPTION (provided by applicant): Structural defects to skeletal muscle range from the relatively benign to the profoundly debilitating. Malformations of this tissue may evolve as a result of a developmental abnormality or as a consequence of traumatic injury. Regardless of the source, structural defects to the skeletal muscle can affect a patient on a number of different levels. For example, a structural defect to the musculature of the face may have a minor impact on the ability of a patient to survive. However, even a minor cosmetic defect can have profound psychological implications. Defects to the muscles of the axial skeleton can limit mobility and thereby reduce quality of life. An overlooked area of craniofacial repair is the field of tissue engineering skeletal muscle prostheses. The objective of this proposal is to engineer a biological implant that can be used to restore structure and function to dysfunctional skeletal muscle. Ideally, such prosthesis should be composed of skeletal muscle myotubes arranged in a pattern equivalent to intact muscle. The engineered tissue should be malleable so that it is possible to sculpt the tissue to restore the contours of missing or damaged muscle. In the preliminary data section of this proposal, we present evidence that we have successfully constructed a multilayered culture of skeletal myocytes derived from neonatal satellite cells that exhibit a three dimensional, tissue-like pattern of organization. We propose to build upon these preliminary experiments to develop a three-dimensional skeletal muscle construct that is pre-adapted to the in vivo environment and is suitable for transplantation and repair of a skeletal muscle defect. The Specific Aims of this proposal are: 1). To produce skeletal muscle constructs that mimic the structure and function of adult skeletal muscle and are pre-adapted to the in vivo environment. 2). To characterize the engineered three-dimensional skeletal muscle constructs with respect to intact tissue using morphological, biochemical, molecular and physiological techniques.