Engineering Skeletal Muscle WIth Biodegradable Hydrogels

用可生物降解水凝胶工程骨骼肌

• 批准号: 9894440
• 负责人: David J Mooney
• 金额: $ 2.97万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-12 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9894440
• 关键词: Address; Animals; Biocompatible Materials; Cells; Cues; Development; Disease; Engineering; Environment; Excision; Frequencies; Funding; Goals; Hydrogels; Immune; Immune system; Infiltration; Injury; Ischemia; Malignant Neoplasms; Mechanical Stimulation; Mechanics; Muscle; Muscle satellite cell; Muscular Atrophy; Natural regeneration; Organ; Patients; Periodicity; Reconstructive Surgical Procedures; Recovery; Regenerative Medicine; Regulation; Research; Role; Site; Skeletal Muscle; T-Lymphocyte; Technology; Tissue Engineering; Tissues; Trauma; Work; craniofacial; cytokine; injured; macrophage; morphogens; mouse model; muscle regeneration; muscle transplantation; reconstitution; robotic device; robotic system; spatiotemporal; success; tissue regeneration

Skeletal muscle tissue is often required in reconstructive surgery following trauma or resection due to cancer, and the long-term goal of the applicants' research is to regenerate functional craniofacial skeletal muscle. The role of direct mechanical stimulation of damaged muscle tissue has largely been ignored in tissue engineering and regenerative medicine efforts to date, in spite of the clear mechanical role and responsiveness of muscle. We have recently demonstrated that cyclic mechanical compression dramatically enhances muscle regeneration, leading to rapid recovery following serious injury in a mouse model of combined direct muscle injury and ischemia. While the mechanism(s) underlying these effects remain unclear, the impact of mechanical stimulation on regeneration correlates to alterations in immune cell infiltration of the muscle; further, direct manipulation of local immune cell activity at the injury site enhances functional muscle regeneration. The specific hypothesis guiding this application is that cyclic mechanical strain imposed via a soft robotic device enhances muscle regeneration via alteration of the immune cell repertoire at the injury site. The hypothesis will be addressed with the following aims: 1. Optimize the regime of mechanical stimulation applied to injured muscle via the development of a new soft robotic system that allows one to simultaneously treat multiple animals in parallel with control over the amplitude, frequency, and duration of stimulation. 2. Delineate the mechanism(s) underlying the mechanically-driven regeneration, focusing on the role of immune cells in the damaged tissue. 3. Reconstitute a similar profile of immune cell activity without mechanical stimulation, and study the impact on muscle regeneration. The successful completion of these aims will lead to a new strategy for the regeneration and return to function of damaged muscle tissue. This work will have significant relevance in craniofacial reconstructive surgery, and also apply to the regeneration of muscle throughout the body. In a broader sense, the concepts explored in this proposal are likely to be broadly applicable to other tissues and organs in the body.

骨骼肌组织通常需要在创伤或癌症切除后的重建手术中， 申请人研究的长期目标是再生功能性颅面骨骼肌。的 在组织工程中，直接机械刺激受损肌肉组织的作用在很大程度上被忽视 和再生医学的努力，尽管明确的机械作用和肌肉的反应。 我们最近已经证明，循环机械压缩显着提高肌肉 再生，导致在小鼠模型中严重损伤后的快速恢复， 损伤和局部缺血。虽然这些影响背后的机制尚不清楚，但 对再生的机械刺激与肌肉的免疫细胞浸润的改变相关; 此外，直接操纵损伤部位的局部免疫细胞活性， 再生指导本申请的具体假设是，通过机械应变施加的循环机械应变是由机械应变引起的。 软机器人装置通过改变损伤部位的免疫细胞库来增强肌肉再生。 该假设将解决以下目标：1。优化机械刺激方案 通过开发一种新的软机器人系统， 平行治疗多只动物，同时控制刺激的幅度、频率和持续时间。 2.描述机械驱动再生的机制，重点是 受损组织中的免疫细胞3.重建类似的免疫细胞活性谱， 刺激，并研究对肌肉再生的影响。这些目标的成功实现将导致 一种新的策略，用于受损肌肉组织的再生和恢复功能。这项工作将有 在颅面重建手术中有显著相关性，也适用于肌肉再生 在整个身体。从更广泛的意义上说，本提案中探讨的概念可能广泛地 适用于身体的其他组织和器官。