PDGF-BB/SA/Dex injectable hydrogels accelerate BMSC-mediated functional full thickness skin wound repair by promoting angiogenesis

被引：32
作者：
Zhang, Zhenkun [1 ]
Li, Zhe [1 ]
Wang, Yingying [1 ]
Wang, Qianqian [1 ]
Yao, Minghao [1 ]
Zhao, Liang [2 ]
Shi, Jijing [3 ]
Guan, Fangxia [1 ,3 ]
Ma, Shanshan [1 ]
机构：
[1] Zhengzhou Univ, Sch Life Sci, 100 Sci Ave, Zhengzhou 450001, Henan, Peoples R China
[2] Henan Inst Populat & Reprod Hlth, Natl Hlth Commiss, Key Lab Birth Defects Prevent, Zhengzhou 450002, Henan, Peoples R China
[3] First Peoples Hosp Zhengzhou, Key Med Lab Stem Cell Transformat & Applicat, Zhengzhou 450000, Henan, Peoples R China
来源：
JOURNAL OF MATERIALS CHEMISTRY B | 2021年 / 9卷 / 31期
基金：
中国国家自然科学基金;
关键词：
MESENCHYMAL STEM-CELLS; ENDOTHELIAL-CELLS; VESSEL FORMATION; INJURY; SYSTEM; BETA;
D O I：
10.1039/d1tb00952d
中图分类号：
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号：
0805 ; 080501 ; 080502 ;
摘要：
Wound healing is a well-orchestrated dynamic and interactive process, which needs a favorable microenvironment and suitable angiogenesis. Platelet derived growth factor-BB (PDGF-BB) plays a crucial role in wound healing. However, the short half-life of PDGF-BB limits its efficacy. In the present study, we successfully synthesized an injectable hydrogel with sodium alginate (SA) and dextran (Dex) as a delivery system to simultaneously deliver PDGF-BB and bone marrow-derived mesenchymal stem cells (BMSCs) in the wound. Our work demonstrates that the PDGF-BB protein enhanced the survival, migration and endothelial cell (EC) differentiation of BMSCs in vitro. The PDGF-BB/SA/Dex hydrogels could sustainably release PDGF-BB with excellent biocompatibility in vitro and in vivo. Besides, these composite hydrogels loaded with BMSCs could accelerate wound healing by improving epithelialization and collagen deposition. In addition, the PDGF-BB/SA/Dex hydrogels promoted the EC-differentiation of transplanted BMSCs and proliferation of hair follicle stem cells in the wound. Furthermore, the expressions of angiogenesis-specific markers, PDGFR-beta, p-PI3K, p-Akt, and p-eNOS, were obviously increased in the PDGF-BB/SA/Dex/BMSCs group. In conclusion, the PDGF-BB/SA/Dex injectable hydrogels could accelerate BMSC-mediated skin wound healing by promoting angiogenesis via the activation of the PDGF-BB/PDGFR-beta-mediated PI3K/Akt/eNOS pathway, which may provide a new therapeutic strategy for stem cell therapy in wound healing.
引用
收藏
页码：6176 / 6189
页数：14
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