Conductive self-healing biodegradable hydrogel based on hyaluronic acid-grafted-polyaniline as cell recruitment niches and cell delivery carrier for myogenic differentiation and skeletal muscle regeneration

Scaffold is one of the most important roles in skeletal muscle tissue engineering. Being capable of mimicking extracellular matrix components, having electrical conductivity, and recruiting cells proactively to meet the cell-free requests are the proper characteristics of tissue engineering scaffolds. In this work, a series of leucine (Leu) loaded self-healing conductive hydrogels based on aminated hyaluronic acid-graft-polyaniline (AHA-PANI) and oxidized hyaluronic (OHA) were prepared for skeletal muscle tissue engineering. Leu can promote skeletal myogenesis and hydrogel can provide a suitable growth environment for cells. They have self-healing properties, antioxidant activity, suitable modulus, good electrical conductivity, high porosity, and proper swelling ratio. Additionally, these hydrogels have good cytocompatibility and can provide a 3D culture environment for C2C12 and hADSC cells. The Leu-loaded hydrogel has recruiting ability of cells and can promote myogenic differentiation of C2C12 cells. Besides, these hydrogels enable sustained cell delivery, and have good in vivo degradability and exhibited promoting effect on skeletal muscle regeneration in the rat tibialis anterior muscle defect model with reduced post-repair inflammatory factor expression and enhanced myogenic differentiation-related gene expression. All the results indicated that these conductive hydrogels as self-healing cell recruitment niches are excellent biomaterial for the treatment of volumetric muscle loss injury.