Injectable thermo-responsive Poloxamer hydrogel/methacrylate gelatin microgels stimulates bone regeneration through biomimetic programmed release of SDF-1a and IGF-1

自愈水凝胶 明胶 化学 再生(生物学) 控制释放 细胞生物学 MAPK/ERK通路 间充质干细胞 间质细胞 生物医学工程 材料科学 生物物理学 激酶 纳米技术 癌症研究 生物化学 生物 医学 高分子化学
作者
Qiang Zhong,Ding Wang,Huaming Mai,Rong Chen,Yixin Xu,Mingyuan Lei,Jiajun Xie,Zinan Tang,Jinlang Fu,Yuhang Chen,Jian Wang,Zhanjun Shi,Hao Cheng
出处
期刊:International Journal of Biological Macromolecules [Elsevier]
卷期号:271: 132742-132742
标识
DOI:10.1016/j.ijbiomac.2024.132742
摘要

Injectable hydrogels, offering adaptable drug delivery of growth factors (GFs), hold promise for treating bone defects. To optimize osteogenic efficacy, the release of GFs should mirror the natural bone healing. We developed an injectable thermo-responsive hydrogel/microgels platform for dual GF delivery for bone regeneration. Stromal cell-derived factor-1 alpha (SDF-1a) and the Methacrylate Gelatin (GelMA) microgels which encapsulated insulin-like growth factor-1 (IGF-1) loaded liposomes (Ls) were introduced into Poloxamer 407 (P407) hydrogel matrix. This system achieved the biomimetic release profile of SDF-1a and IGF-1, which covered the early stage from day 1 to 7 and the continuous stage from day 5 to 21, respectively. In vitro study confirmed the enhanced migration, osteogenic biomarker expression, and matrix mineralization of the bone marrow mesenchymal stem cells (BMSCs) co-cultivated with the dual GFs delivering hydrogel/microgels. Transcriptome sequencing revealed that the potential mechanism was associated with mitogen-activated protein kinase (MAPK) signaling activation and its downstream ribosomal protein S6 kinase 2 (RSK2) upregulation. In a critical-sized calvarial defect model in Sprague-Dawley (SD) rats, the injectable hydrogel/microgels system promoted significant bone regeneration. Collectively, our study suggested the current hydrogel/microgels system with the biomimetic release of SDF-1a and IGF-1 efficiently promoted bone regeneration, informing the future development of GF delivery systems intended for bone regeneration therapies.
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