In skeletal-muscle regeneration, it is critical to promote efferocytosis of immune cells and differentiation of satellite cells/postnatal muscle stem cells at the damaged sites. With the optimized poloxamer 407 composition gelled at body temperature, the drugs can be delivered locally. The purpose of this study is to develop a topical injection therapeutic agent for muscle regeneration, sarcopenia, and cachexia. Herein, we construct an injectable, in situ hydrogel system consisting of CD146, IGF-1, collagen I/III, and poloxamer 407, termed CIC gel. The secreted CD146 then binds to VEGFR2 on the muscle surface and effectively induces efferocytosis of neutrophils and macrophages. IGF-1 promotes satellite cell differentiation, and biocompatible collagen evades immune responses of the CIC gel. Consequently, these combined molecules activate muscle regeneration via autophagy and suppress muscle inflammation and apoptosis. Conclusively, we provide an applicable concept of the myogenesis-activating protein formulation, broadening the thermoreversible hydrogel to protein therapeutics for damaged muscle recovery.
|Number of pages||11|
|Journal||ACS Applied Bio Materials|
|Publication status||Published - 2021 Sept 20|
Bibliographical noteFunding Information:
This study was supported by a grant from the Korea Research Institute of Bioscience and Biotechnology Research Initiative Program (KGM3141824 and OGM4391913), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C0001), and National Research Foundation of Korea (NRF) grants funded by the Ministry of Science and ICT (NRF-2018R1A2B3004266 and NRF-2018R1C1B6005379).
All Science Journal Classification (ASJC) codes
- Biochemistry, medical
- Biomedical Engineering