Injectable muscle-adhesive antioxidant conductive photothermal bioactive nanomatrix for efficiently promoting full-thickness skeletal muscle regeneration

Abstract

The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge. Here, we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-responsive nanomatrix for regulating the myogenic differentiation and promoting the skeletal muscle regeneration in vivo . The multifunctional nanomatrix was composed of polypyrrole@polydopamine (PPy@PDA, 342 ± 5.6 nm) nanoparticles-crosslinked Pluronic F-127 (F127)-polycitrate matrix (FPCP). The FPCP nanomatrix demonstrated inherent multifunctional properties including excellent photothermo-responsive and shear-thinning behavior, muscle-adhesive feature, injectable ability, electronic conductivity (0.48 ± 0.03 S/m) and antioxidant activity and photothermal function. The FPCP nanomatrix displayed better photothermal performance with near-infrared irradiation, which could provide the photo-controlled release of protein (91% ± 2.6% of BSA was released after irradiated 3 times). Additionally, FPCP nanomatrix could significantly enhance the cell proliferation and myogenic differentiation of mouse myoblast cells (C2C12) by promoting the expressions of myogenic genes (MyoD and MyoG) and myosin heavy chain (MHC) protein with negligible cytotoxicity. Based on the multifunctional properties, FPCP nanomatrix efficiently promoted the full-thickness skeletal muscle repair and regeneration in vivo , through stimulating the angiogenesis and myotube formation. This study firstly indicated the vital role of multifunctional PPy@PDA nanoparticles in regulating myogenic differentiation and skeletal muscle regeneration. This work also suggests that rational design of bioactive matrix with multifunctional feature would greatly enhance the development of regenerative medicine.

A Review on Hydrogels with Photothermal Effect in Wound Healing and Bone Tissue Engineering

“…Organic materials with photothermal conversion ability have also received extensive attention because of their good degradation properties and excellent biocompatibility. Research studies on organic photothermal conversion materials focused on dyes such as IR-820 [71,72], IR-780 [73,74], indocyanine green (ICG) [75], and conjugated polymers such as poly-dopamine (PDA) [76,77], poly-pyrrole [78,79], and poly-aniline [80]. Dopamine (DA), as a material with excellent photothermal conversion and adhesion abilities, has attracted increasing attention.…”

Current Strategies for the Regeneration of Skeletal Muscle Tissue

“…In current clinical treatments, the transplantation of allogeneic muscle cells is significantly limited due to rejection reactions, donor site morbidity, and insufficient donor cells [ 121 ]. In addition, the delivery and retention of cells in muscle are inefficient, hindering the sustained regeneration required for sufficient functional improvement [ 122 , 123 ].…”

3D bioprinting of conductive hydrogel for enhanced myogenic differentiation

“…Following the formation and maturation of myotubes, myofilament organization, as well as ECM remodeling, the muscle tissue enters the final phase of the regeneration process [ 21–23 ]. Despite the success in harboring the cells, the growth and function of cells are affected by the required electrical signals in muscle tissues [ 24 , 25 ]. Basically, the bioelectrical character of the applied biomaterial may directly influence the migration and fusion of C2C12 cells.…”

“…Recently, the application of various conductive polymers, such as polyaniline (PANi), polypyrene, and polythiophene, has been widely investigated [ 24 , 25 , 36 , 37 ]. The conductivity of these polymers comes from the conjugated double bonds along the main chain and π electrons in the main chain that can delocalize to form a conductive band [ 38 , 39 ].…”