Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90064, USA.
Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, Los Angeles, CA, 90095, USA.
Macromol Biosci. 2023 Dec;23(12):e2300276. doi: 10.1002/mabi.202300276. Epub 2023 Aug 17.
Several microfabrication technologies have been used to engineer native-like skeletal muscle tissues. However, the successful development of muscle remains a significant challenge in the tissue engineering field. Muscle tissue engineering aims to combine muscle precursor cells aligned within a highly organized 3D structure and biological factors crucial to support cell differentiation and maturation into functional myotubes and myofibers. In this study, the use of 3D bioprinting is proposed for the fabrication of muscle tissues using gelatin methacryloyl (GelMA) incorporating sustained insulin-like growth factor-1 (IGF-1)-releasing microparticles and myoblast cells. This study hypothesizes that functional and mature myotubes will be obtained more efficiently using a bioink that can release IGF-1 sustainably for in vitro muscle engineering. Synthesized microfluidic-assisted polymeric microparticles demonstrate successful adsorption of IGF-1 and sustained release of IGF-1 at physiological pH for at least 21 days. Incorporating the IGF-1-releasing microparticles in the GelMA bioink assisted in promoting the alignment of myoblasts and differentiation into myotubes. Furthermore, the myotubes show spontaneous contraction in the muscle constructs bioprinted with IGF-1-releasing bioink. The proposed bioprinting strategy aims to improve the development of new therapies applied to the regeneration and maturation of muscle tissues.
已经有几种微制造技术被用于构建类似天然的骨骼肌组织。然而,成功地开发肌肉仍然是组织工程领域的一个重大挑战。肌肉组织工程旨在将肌肉前体细胞排列在高度组织化的 3D 结构中,并结合对支持细胞分化和成熟为功能性肌管和肌纤维至关重要的生物因素。在这项研究中,提出了使用 3D 生物打印技术来制造肌肉组织,使用含有持续释放胰岛素样生长因子-1(IGF-1)的明胶甲基丙烯酰(GelMA)和肌母细胞的微球。本研究假设,使用能够持续释放 IGF-1 的生物墨水进行体外肌肉工程,将更有效地获得功能成熟的肌管。合成的微流控辅助聚合物微球成功地吸附了 IGF-1,并在生理 pH 下至少持续释放 21 天的 IGF-1。将释放 IGF-1 的微球掺入 GelMA 生物墨水中有助于促进肌母细胞的排列和向肌管的分化。此外,在含有释放 IGF-1 的生物墨水中生物打印的肌肉构建体中,肌管显示出自发的收缩。所提出的生物打印策略旨在改善应用于肌肉组织再生和成熟的新疗法的发展。