Enhanced Maturation of 3D Bioprinted Skeletal Muscle Tissue Constructs Encapsulating Soluble Factor-Releasing Microparticles

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.

keywords

GELATIN METHACRYLOYL GELMA; GROWTH-FACTOR-I; PLGA MICROSPHERES; LADEN HYDROGELS; REGENERATION; DIFFERENTIATION; DELIVERY; VITRO

subject category

Biochemistry & Molecular Biology; Materials Science; Polymer Science

authors

de Barros, NR; Darabi, MA; Ma, X; Diltemiz, SE; Ermis, M; Najafabadi, A; Nadine, S; Banton, EA; Mandal, K; Abbasgholizadeh, R; Falcone, N; Mano, JF; Nasiri, R; Herculano, RD; Zhu, YZ; Ostrovidov, S; Lee, JM; Kim, HJ; Hosseini, V; Dokmeci, MR; Ahadian, S; Khademhosseini, A

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

acknowledgements

The authors acknowledge funding from the National Institutes of Health & nbsp;(AR073135, 1R01DK130566-01, and 1R01CA257558-01). S.N. would like to acknowledge the Fundacao para a Ciencia e a Tecnologia: UIDB/50011/2020; UIDP/50011/2020; LA/P/0006/2020. H-J.K. would like to acknowledge the Basic Science Research Program through the National Research Foundation (NRF), funded by the Ministry of Education (RS-2023-00240729) and the MSIT (Ministry of Science and ICT), Korea, under the ITRC (Information Technology Research Center) support program (IITP-2023-RS-2023-00258971) supervised by the IITP (Institute for Information & Communications Technology Planning & Evaluation).