Thermosensitive Hydrogel Harboring CD146/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration

Wonhwa Lee; Jae Young Lee; Han Sol Lee; Youngbum Yoo; Hyosoo Shin; Hyelim Kim; Do Sik Min; Jong Sup Bae; Young Kyo Seo

doi:10.1021/acsabm.1c00688

Thermosensitive Hydrogel Harboring CD146/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration

Wonhwa Lee, Jae Young Lee, Han Sol Lee, Youngbum Yoo, Hyosoo Shin, Hyelim Kim, Do Sik Min, Jong Sup Bae, Young Kyo Seo

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	7070-7080
Number of pages	11
Journal	ACS Applied Bio Materials
Volume	4
Issue number	9
DOIs	https://doi.org/10.1021/acsabm.1c00688
Publication status	Published - 2021 Sept 20

Bibliographical note

Funding 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).

Publisher Copyright:
©

All Science Journal Classification (ASJC) codes

Biochemistry, medical
Chemistry(all)
Biomedical Engineering
Biomaterials

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title = "Thermosensitive Hydrogel Harboring CD146/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration",

abstract = "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.",

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note = "Funding 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). Publisher Copyright: {\textcopyright} ",

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AU - Kim, Hyelim

AU - Min, Do Sik

AU - Bae, Jong Sup

AU - Seo, Young Kyo

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PY - 2021/9/20

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N2 - 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.

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Thermosensitive Hydrogel Harboring CD146/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration

Abstract

Bibliographical note

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