Engineering a Muscle Mimetic Biomaterial

在美国，每年大约有40万例肩袖手术。在运营期间 技术已经改进，肩袖修复后的再破裂率仍然很高(30%-35%)。一个 肌腱再断裂的公认危险因素是肩袖肌肉退行性萎缩。我们建议一个 现成的“现成”生物材料，通过模仿 天然骨骼肌细胞外基质的特性可用于损伤肌肉组织的再生。 为了创造一种组织模拟材料，我们开发了一种创新的方法来捕获分泌的细胞外基质 根据细胞在体外生长过程中的数量。这种方法使我们能够设计出像本地材料一样的材料 组织，完全由细胞衍生的成分组成。这项研究建议的假设是，我们 可以使用这种ECM收集方法构建工程肌肉模拟(EMM)支架，该支架能够 再生受损的骨骼肌。以下具体目标描述了一个发展过程，在这个过程中 Emm支架的设计将以天然肌肉组织的特性为指导。也就是说，骨骼肌 将制备样品并对其进行彻底表征，以作为设计模板(目标1)。我们将利用 我们的细胞外基质收集方法捕获肌肉细胞分泌的细胞外基质并将其组织成肌膜支架 具有肌肉模拟成分和结构(目标2)。我们将测试ECM的再生性能 使用肌肉缺陷模型的支架(目标3)。

Each year approximately 400,000 rotator cuff surgeries are performed in the United States. While operative techniques have improved, the re-rupture rate following rotator cuff repair remains high (30-35%). A recognized risk factor for tendon re-rupture is rotator cuff muscle degenerative atrophy. We suggest that a readily available "off the shelf" biomaterial that provides the appropriate regenerative cues by mimicking the properties of native skeletal muscle extracellular matrix could be used to regenerate damaged muscle tissue. To create a tissue mimetic material we have developed an innovative approach to capture the ECM secreted by populations of cells during growth in-vitro. This approach allows us to engineer materials that, like native tissues, are comprised entirely of cell derived constituents. The hypothesis of this research proposal is that we can use this ECM collection approach to build an engineered muscle mimetic (eMM) scaffold capable of regenerating damaged skeletal muscle. The following specific aims describe a development process in which the design of eMM scaffolds will be guided by the properties of native muscle tissue. Namely, skeletal muscle samples will be prepared and thoroughly characterized to serve as a design template (Aim 1). We will utilize our ECM collection approach to capture and organize the ECM secreted by muscle cells into an eMM scaffold with muscle mimetic composition and structure (Aim 2). We will test the regenerative performance of ECM scaffolds using a muscle defect model (Aim 3).