Borax-loaded injectable alginate hydrogels promote muscle regeneration in vivo after an injury

[EN] Muscle tissue possess an innate regenerative potential that involves an extremely complicated and synchronized process on which resident muscle stem cells play a major role: activate after an injury, differentiate and fuse originating new myofibers for muscle repair. Considerable efforts have been made to design new approaches based on material systems to potentiate muscle repair by engineering muscle extracellular matrix and/or including soluble factors/cells in the media, trying to recapitulate the key biophysical and biochemical cues present in the muscle niche. This work proposes a different and simple approach to potentiate muscle regeneration exploiting the interplay between specific cell membrane receptors. The simultaneous stimulation of borate transporter, NaBC1 (encoded by SLC4A11gene), and fibronectin-binding integrins induced higher number and size of focal adhesions, major cell spreading and actin stress fibers, strengthening myoblast attachment and providing an enhanced response in terms of myotube fusion and maturation. The stimulated NaBC1 generated an adhesion-driven state through a mechanism that involves simultaneous NaBC1/?5?1/?v?3 co-localization. We engineered and characterized borax-loaded alginate hydrogels for an effective activation of NaBC1 in vivo. After inducing an acute injury with cardiotoxin in mice, active-NaBC1 accelerated the muscle regeneration process. Our results put forward a new biomaterial approach for muscle repair. PR acknowledges support from the Spanish Ministry of Science, Innovation and Universities (RTI2018096794) , and Fondo Europeo de Desarrollo Regional (FEDER) . CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors wish to thank also the intellectual and technical assistance from the ICTS "NANBIOSIS", more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/EHU) . The authors are grateful to A. Miralles for the credit of image of the mouse included in the graphical abstract. Ciriza, J.; Rodriguez-Romano, A.; Nogueroles, I.; Gallego-Ferrer, G.; Martín Cabezuelo, R.; Pedraz, JL.; Rico Tortosa, PM. (2021). Borax-loaded injectable alginate hydrogels promote muscle regeneration in vivo after an inju