Kang Moon Sung, Yu Yeuni, Park Rowoon, Heo Hye Jin, Lee Seok Hyun, Hong Suck Won, Kim Yun Hak, Han Dong-Wook
Department of Cogno-Mechatronics Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan, 46241, Republic of Korea.
Medical Research Institute, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.
Nanomicro Lett. 2024 Jan 4;16(1):73. doi: 10.1007/s40820-023-01293-1.
Current therapeutic approaches for volumetric muscle loss (VML) face challenges due to limited graft availability and insufficient bioactivities. To overcome these limitations, tissue-engineered scaffolds have emerged as a promising alternative. In this study, we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone) integrated with collagen and TiCT MXene nanoparticles (NPs) (PCM matrices), and explored their myogenic potential for skeletal muscle tissue regeneration. The PCM matrices demonstrated favorable physicochemical properties, including structural uniformity, alignment, microporosity, and hydrophilicity. In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts. Moreover, in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury. Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices, leading to elevated intracellular Ca levels in myoblasts through the activation of inducible nitric oxide synthase (iNOS) and serum/glucocorticoid regulated kinase 1 (SGK1), ultimately promoting myogenic differentiation via the mTOR-AKT pathway. Additionally, upregulated iNOS and increased NO contributed to myoblast proliferation and fiber fusion, thereby facilitating overall myoblast maturation. These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.
由于移植物可用性有限和生物活性不足，目前针对容积性肌肉损失（VML）的治疗方法面临挑战。为了克服这些限制，组织工程支架已成为一种有前途的替代方案。在本研究中，我们开发了由聚（丙交酯-共-ε-己内酯）与胶原蛋白和TiCT MXene纳米颗粒（NPs）整合而成的排列整齐的三元纳米纤维基质（PCM基质），并探索了它们在骨骼肌组织再生中的成肌潜力。PCM基质表现出良好的物理化学性质，包括结构均匀性、排列、微孔性和亲水性。体外试验表明，PCM基质促进了C2C12成肌细胞的细胞行为和成肌分化。此外，体内实验表明，在VML损伤后用PCM基质治疗的小鼠中，肌肉重塑和恢复得到增强。下一代测序的机制见解表明，MXene NPs促进了PCM基质内蛋白质和离子的可用性，通过诱导型一氧化氮合酶（iNOS）和血清/糖皮质激素调节激酶1（SGK1）的激活导致成肌细胞内Ca水平升高，最终通过mTOR-AKT途径促进成肌分化。此外，iNOS的上调和NO的增加促进了成肌细胞的增殖和纤维融合，从而促进了成肌细胞的整体成熟。这些发现强调了负载在高度排列基质中的MXene NPs作为促进骨骼肌组织恢复的治疗剂的潜力。
