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Thermosensitive Hydrogel Harboring CD146/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2021-08-23 , DOI: 10.1021/acsabm.1c00688
Wonhwa Lee 1, 2 , Jae-Young Lee 3 , Han Sol Lee 3 , Youngbum Yoo 1 , Hyosoo Shin 1 , Hyelim Kim 3 , Do Sik Min 4 , Jong-Sup Bae 2 , Young-Kyo Seo 1
Affiliation  

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.

中文翻译:

含有 CD146/IGF-1 纳米颗粒的热敏水凝胶用于骨骼肌肉再生

在骨骼肌再生中,促进受损部位的免疫细胞胞吐作用和卫星细胞/出生后肌肉干细胞的分化至关重要。通过优化的泊洛沙姆 407 组合物在体温下凝胶化,药物可以局部给药。本研究的目的是开发一种用于肌肉再生、肌肉减少症和恶病质的局部注射治疗剂。在这里,我们构建了一种可注射的原位由 CD146、IGF-1、胶原蛋白 I/III 和泊洛沙姆 407 组成的水凝胶系统,称为 CIC 凝胶。分泌的 CD146 然后与肌肉表面的 VEGFR2 结合,并有效地诱导嗜中性粒细胞和巨噬细胞的胞吐作用。IGF-1 促进卫星细胞分化,生物相容性胶原蛋白逃避 CIC 凝胶的免疫反应。因此,这些组合分子通过自噬激活肌肉再生并抑制肌肉炎症和细胞凋亡。最后,我们提供了肌生成激活蛋白配方的适用概念,将热可逆水凝胶扩展到用于受损肌肉恢复的蛋白质疗法。
更新日期:2021-09-20
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