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Updated: Jul 19, 2025
Intramyocardial Transplantation of MSC-Loading Injectable Hydrogels after Myocardial Infarction in a Murine Model
Published on: September 20, 2020
A Double Cross-Linked Injectable Hydrogel Derived from Muscular Decellularized Matrix Promotes Myoblast Proliferation
Zhao Huang1, Jianwen Cheng1, Wei Su1
1Department of Orthopedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Abstract:
Injectable hydrogels possess tremendous merits for use in muscle regeneration; however, they still lack intrinsic biological cues (such as the proliferation and differentiation of myogenic cells), thus considerably restricting their potential for therapeutic use. Herein, we developed a double cross-linked injectable hydrogel composed of methacrylamidated oxidized hyaluronic acid (MOHA) and muscular decellularized matrix (MDM). The chemical composition of the hydrogel was confirmed using 1H NMR and Fourier transform infrared spectroscopy. To achieve cross-linking, the aldehyde groups in MOHA were initially reacted with the amino groups in MDM through a Schiff-based reaction. This relatively weak cross-linking provided the MOHA/MDM hydrogel with satisfactory injectability. Furthermore, the methacrylation of MOHA facilitated a second cross-linking mechanism via UV irradiation, resulting in improved gelation ability, biomechanical properties, and swelling performance. When C2C12 myogenic cells were loaded into the hydrogel, our results showed that the addition of MDM significantly enhanced myoblast proliferation compared to the MOHA hydrogel, as demonstrated by live/dead staining and Cell Counting Kit-8 assay after seven days of in vitro cultivation. In addition, gene expression analysis using quantitative polymerase chain reaction indicated that the MOHA/MDM hydrogel promoted myogenic differentiation of C2C12 cells more effectively than the MOHA hydrogel, as evidenced by elevated expression levels of myogenin, troponin T, and MHC in the MOHA/MDM hydrogel group. Moreover, after four to eight weeks of implantation in a full-thickness abdominal wall-defect model, the MOHA/MDM hydrogel could promote the reconstruction and repair of functional skeletal muscle tissue with enhanced tetanic force and tensile strength. This study provides a new double cross-linked injectable hydrogel for use in muscular tissue engineering.
