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/α₅β₁/α_vβ₃ 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.

肌肉组织具有先天的再生潜力，涉及一个极其复杂和同步的过程，其中驻留的肌肉干细胞发挥着重要作用：受伤后激活，分化和融合产生新的肌纤维以进行肌肉修复。人们已经做出了大量努力来设计基于材料系统的新方法，通过工程肌肉细胞外基质和/或在培养基中包含可溶性因子/细胞来增强肌肉修复，试图概括肌肉生态位中存在的关键生物物理和生化线索。这项工作提出了一种不同且简单的方法，利用特定细胞膜受体之间的相互作用来增强肌肉再生。同时刺激硼酸转运蛋白、NaBC1（由SLC4A11基因编码）和纤连蛋白结合整合素可诱导更多数量和大小的粘着斑、主要细胞扩散和肌动蛋白应力纤维，从而加强成肌细胞附着并增强肌管融合的反应和成熟。_{受刺激的 NaBC1 通过涉及同时 NaBC1/α 5} β ₁ /α _v β ₃共定位的机制产生粘附驱动状态。我们设计并表征了负载硼砂的藻酸盐水凝胶，以在体内有效激活 NaBC1 。在用心脏毒素诱导小鼠急性损伤后，活性 NaBC1 加速了肌肉再生过程。我们的研究结果提出了一种用于肌肉修复的新生物材料方法。