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.

由于癌症引起的创伤或切除后，经常需要骨骼肌组织重建手术， 申请人研究的长期目标是再生功能性颅面骨骼肌。这 在组织工程中，直接机械刺激受损的肌肉组织的作用在很大程度上被忽略了 尽管肌肉的机械作用和反应性明确，但迄今为止的再生医学努力。 我们最近证明，环状机械压缩极大地增强了肌肉 再生，导致在直接肌肉的小鼠模型中严重受伤后迅速恢复 受伤和缺血。尽管这些作用的基础机制尚不清楚，但 对再生的机械刺激与肌肉免疫细胞浸润的改变相关。 此外，在损伤部位直接操纵局部免疫细胞活性会增强功能性肌肉 再生。指导该应用的特定假设是通过A施加的环状机械应变 软机器人装置通过改变伤害部位的免疫细胞库来增强肌肉再生。 该假设将以以下目的解决：1。优化机械刺激的状态 通过开发新的软机器人系统应用于受伤的肌肉，该系统可以同时使用 与控制幅度，频率和刺激持续时间的控制同行治疗多动物。 2。描述机械驱动的再生的基础机制，重点是 受损组织中的免疫细胞。 3。重建没有机械的免疫细胞活性的类似特征 刺激并研究对肌肉再生的影响。这些目标的成功完成将导致 一种新的策略，用于再生并恢复受损的肌肉组织的功能。这项工作将有 在颅面重建手术中有很大的相关性，也适用于肌肉的再生 整个身体。从广义上讲，本提案中探讨的概念可能是广泛的 适用于体内其他组织和器官。