John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Nat Mater. 2023 Feb;22(2):249-259. doi: 10.1038/s41563-022-01396-x. Epub 2022 Nov 10.
While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and rehabilitation has been limited by the availability of suitable devices. Here we present a mechanically active gel-elastomer-nitinol tissue adhesive (MAGENTA) that generates and delivers muscle-contraction-mimicking stimulation to a target tissue with programmed strength and frequency. MAGENTA consists of a shape memory alloy spring that enables actuation up to 40% strain, and an adhesive that efficiently transmits the actuation to the underlying tissue. MAGENTA activates mechanosensing pathways involving yes-associated protein and myocardin-related transcription factor A, and increases the rate of muscle protein synthesis. Disuse muscles treated with MAGENTA exhibit greater size and weight, and generate higher forces compared to untreated muscles, demonstrating the prevention of atrophy. MAGENTA thus has promising applications in the treatment of muscle atrophy and regenerative medicine.
虽然机械刺激已被证实可在细胞和组织水平上调节广泛的生物学过程,但由于缺乏合适的装置,其在组织再生和康复方面的医学应用受到限制。在这里,我们提出了一种机械活性凝胶弹性体镍钛诺组织粘合剂(MAGENTA),它可以产生并以预定的强度和频率向目标组织输送类似于肌肉收缩的刺激。MAGENTA 由形状记忆合金弹簧组成,可实现高达 40%的应变驱动,以及一种可将驱动有效地传递到下面组织的粘合剂。MAGENTA 激活了涉及 yes 相关蛋白和心肌相关转录因子 A 的机械感觉途径,并增加了肌肉蛋白合成的速度。与未经处理的肌肉相比,接受 MAGENTA 治疗的废用肌肉的体积和重量更大,产生的力量也更高,这表明 MAGENTA 可以预防萎缩。因此,MAGENTA 在肌肉萎缩和再生医学的治疗中有很好的应用前景。
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