Enhanced Maturation of 3D Bioprinted Skeletal Muscle Tissue Constructs Encapsulating Soluble Factor‐Releasing Microparticles
Natan Roberto de Barros, Mohammad Ali Darabi, Xin Ma, Sibel Emi̇r Di̇ltemi̇z, Menekşe Ermis, Alireza Hassani Najafabadi, Sara Nadine, Ethan A. Banton, Kalpana Mandal, Reza Abbasgholizadeh, Natashya Falcone, João F. Mano, Rohollah Nasiri, Rondinelli Donizetti Herculano, Yangzhi Zhu, Serge Ostrovidov, Junmin Lee, Han‐Jun Kim, Vahid Hosseini, Mehmet R. Dokmeci, Samad Ahadian, Ali Khademhosseini
Abstract
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.