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

被引：0

作者：

Zhong, Qiang ^{[1
]}

Wang, Ding ^{[1
]}

Mai, Huaming ^{[1
]}

Chen, Rong ^{[1
]}

Xu, Yixin ^{[1
]}

Lei, Mingyuan ^{[1
]}

Xie, Jiajun ^{[1
]}

Tang, Zinan ^{[1
]}

Fu, Jinlang ^{[1
]}

Chen, Yuhang ^{[1
]}

Wang, Jian ^{[1
]}

Shi, Zhanjun ^{[1
]}

Cheng, Hao ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Orthoped, 1838 Guangzhou North Ave, Guangzhou 510515, Guangdong, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2024年 / 271卷

基金：

中国国家自然科学基金;

关键词：

Bone regeneration; Injectable thermo-responsive hydrogel; Biomimetic programmed release; MESENCHYMAL STEM-CELLS; INFLAMMATION; HYDROGEL; REPAIR; MICROENVIRONMENT; ACTIVATION; LIPOSOME; BIOLOGY; GROWTH;

D O I：

10.1016/j.ijbiomac.2024.132742

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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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页数：15