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的到严重衰弱的都有。这种组织的畸形可能是由于发育异常或创伤性损伤的结果。无论来源如何，骨骼肌的结构缺陷都会在许多不同的层面上影响患者。例如，面部肌肉组织的结构缺陷可能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观缺陷也会产生深刻的心理影响。中轴骨骼肌肉的缺陷会限制活动性，从而降低生活质量。颅面修复的一个被忽视的领域是组织工程骨骼肌假体领域。该提案的目的是设计一种生物植入物，可用于恢复功能失调的骨骼肌的结构和功能。理想情况下，这种假体应该由骨骼肌肌管组成，其排列方式相当于完整肌肉。工程化组织应该是可延展的，以便可以雕刻组织以恢复缺失或受损肌肉的轮廓。在本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一个多层培养的骨骼肌细胞来源于新生儿卫星细胞，表现出三维，组织样的组织模式。我们建议建立在这些初步的实验，以开发一个三维的骨骼肌结构，是预先适应体内环境，是适合移植和修复骨骼肌缺损。 该提案的具体目标是： 1）。生产模拟成人骨骼肌结构和功能并预先适应体内环境的骨骼肌构建体。 2）。采用形态学、生物化学、分子生物学和生理学技术对工程化三维骨骼肌构建体进行完整组织的表征。

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.