Engineering skeletal muscle using a humanoid bioreactor platform

使用人形生物反应器平台工程骨骼肌

• 批准号: 2886432
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2886432
• 关键词: Engineering; skeletal; muscle; using; humanoid

Skeletal muscle is the largest organ system in the body by mass and is necessary to generate forces for movement and locomotion. Unlike tendons and ligaments, muscle tissue can easily regenerate itself when subjected to minor injuries. However, irreversible loss of muscle tissue affects thousands of patients per year in the UK alone and can be caused by severe conditions such as myopathy, large trauma (e.g. blast injuries) and removal of cancer tissue. Muscle injuries and diseases are becoming more frequent as our population is aging, which causes an increasing societal and economic burden. As current repair strategies are not satisfactory, the awareness of the need for new repair approached is increasing in academia, in industry and also for end users. Tissue engineering is a promising repair strategy for skeletal muscle. This approach involves the use of biomaterials, cells and bioreactor systems, the combination of which allow control of cell culture conditions to provide physical stimulation to the cell-biomaterial constructs to engineer muscle in vitro. Both mechanical and electrical stimulation are relevant to muscle tissue engineering and have been shown to improve the improve cell proliferation and differentiation.Our research group has extensive experience of biomaterial development and testing, including use of decellularized biological tissues, hydrogels and electrospun materials. We have also recently developed a unique bioreactor system that uses a musculoskeletal humanoid robotic arm to mimic the motion and forces observed at the human shoulder joint and actuate cell-biomaterial constructs (EPSRC-funded Humanoid Bioreactor project, EP/S003509/1). Musculoskeletal humanoids can replicate the inner structures, such as muscles, tendons or bones, and the biomechanics of the human body using strings actuated by electric motors. To develop the humanoid bioreactor platform, we combined these robots with soft, flexible bioreactor chambers that host the cell-biomaterial constructs and maintain them alive for long periods of time. While our efforts have so far been focused on tendon tissue engineering for rotator cuff repair applications, the same platform can be applied to engineer skeletal muscle.This PhD project will focus on applying the humanoid bioreactor system to skeletal muscle tissue engineering. The aim is to determine the importance of physiologically-relevant mechanical stimulation and electrical stimulation for muscle tissue engineering. This will contribute to generating better quality muscle grafts. If such an approach is successful, it will provide a reliable and unlimited source of muscle autografts which would translate into safer and more cost-effective patient care.To achieve this goal, a scaffold able to support skeletal muscle tissue growth will need to be developed, either through muscle decellularization or hydrogel approaches. The existing soft chamber of the humanoid bioreactor, currently employed for tendon tissue engineering, will be adapted to host the novel muscle scaffold, allowing both its mechanical and electrical stimulation. The impact of such stimulations on the colonization of the scaffold by skeletal muscle cells will be investigated. The functionality of the engineered muscles will then need to be evaluated. This highly multidisciplinary project involves various aspects of bioengineering, biology, bioelectronics and biomechanics. Although the end application proposed here is to support the regeneration of large muscle defects, other areas in science could benefit from this project. The development of scaffold or biomaterials using this more physiological platform will be of significant interest to other researchers in the field of tissue engineering, as the strategy could be applied to other tissues. Additionally, this project will contribute to the development of bio-actuators, which would benefit developments in bio-robotics and soft robotics.

骨骼肌是体内最大的器官系统，对于产生运动和运动的力是必要的。与肌腱和韧带不同，肌肉组织在受到轻伤时很容易再生。但是，仅在英国，肌肉组织的不可逆转丧失就会影响每年数千名患者，可能是由于严重的疾病，例如肌病，大创伤（例如爆炸损伤）和去除癌症组织。随着我们的人口衰老，肌肉损伤和疾病变得越来越频繁，这会导致社会和经济负担不断增加。由于当前的维修策略并不令人满意，因此学术界，行业以及最终用户的新维修需求的认识正在增加。组织工程是骨骼肌的有前途的修复策略。这种方法涉及使用生物材料，细胞和生物反应器系统，其组合可以控制细胞培养条件，从而为细胞生物材料构建体提供了体外工程肌肉的物理刺激。机械和电刺激都与肌肉组织工程有关，并已证明可以改善细胞的增殖和分化。您的研究组在生物材料发育和测试方面具有丰富的经验，包括使用脱细胞生物组织，水凝胶和电气传播材料。我们最近还开发了一种独特的生物反应器系统，该系统使用肌肉骨骼类人形体机器人臂来模仿人肩关节和动作细胞生物材料构建体（EPSRC资助的人形生物反应器项目，EP/S003509/1）。肌肉骨骼类人形生物可以使用电动机作用的弦来复制内部结构，例如肌肉，肌腱或骨骼，以及人体的生物力学。为了开发类人形生物反应器平台，我们将这些机器人与柔软的柔性生物反应室结合在一起，可容纳细胞生物材料构建体，并长期保持其活性。迄今为止，我们的努力集中在用于肩袖修复应用的肌腱组织工程上，但可以将同一平台应用于工程师的骨骼肌。该博士学位项目将专注于将人形生物反应器系统应用于骨骼肌组织工程。目的是确定与生理相关的机械刺激和对肌肉组织工程的电刺激的重要性。这将有助于产生更好的肌肉移植物。如果这种方法成功，它将提供可靠且无限的肌肉自体源来源，这些肌肉自体能够转化为更安全，更具成本效益的患者护理。目前用于肌腱组织工程的类人生物反应器的现有软室将适应新型的肌肉支架，从而允许其机械和电刺激。将研究这种刺激对骨骼肌细胞支架定植的影响。然后需要评估工程肌肉的功能。这个高度多学科的项目涉及生物工程，生物学，生物电子学和生物力学的各个方面。尽管此处提出的最终申请是支持大肌肉缺陷的再生，但科学的其他领域可能会从该项目中受益。使用这种更生理的平台的脚手架或生物材料的发展将引起组织工程领域的其他研究人员的重大兴趣，因为该策略可以应用于其他组织。此外，该项目将有助于生物激活者的发展，这将有益于生物界和软机器人技术的发展。