Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration

Qiao Pan; Ruyi Fan; Rui Chen; Jiayi Yuan; Shixuan Chen; Biao Cheng

doi:10.3389/fbioe.2023.1150819

Weakly acidic microenvironment of the wound bed boosting the efficacy of acidic fibroblast growth factor to promote skin regeneration

Front Bioeng Biotechnol. 2023 Mar 1:11:1150819. doi: 10.3389/fbioe.2023.1150819. eCollection 2023.

Authors

Qiao Pan^{1

2}, Ruyi Fan^{3

4}, Rui Chen³, Jiayi Yuan³, Shixuan Chen³, Biao Cheng^{1

2}

Affiliations

¹ The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
² Department of Burn and Plastic Surgery, General Hospital of Southern Theater Command of PLA, Guangzhou, China.
³ Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, China.
⁴ School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Abstract

The pH value within the wound microenvironment influences indirectly and directly all biochemical reactions taking place in the process of skin wound healing. Currently, it is generally believed that a low pH value, such as it is found on normal skin, is favorable for wound regeneration, while some investigations have shown that in fact alkaline microenvironments are required for some healing processes. The role of growth factors in promoting wound healing requires a specific microenvironment. In wound microenvironments of different pH, growth factors with different isoelectric points may have different effects. To explore whether the application of FGF with different isoelectric points in wounds with different pH values interferes with the healing process to different degrees, GelMA hydrogels with different pH values were prepared to maintain the wounds microenvironment with the same pH values, in which aFGF and bFGF were loaded as well. The results show that GelMA hydrogels of different pH values maintained the same pH of the wound microenvironment sustainably on the 4th day. Moreover, aFGF and bFGF promoted skin wound healing to varying degrees in different pH wound microenvironments. In particular, aFGF significantly promoted wound re-epithelialization in a weak acidic microenvironment, while bFGF promoted collagen synthesis and deposition in the early stage of weak acid wounds. In addition, aFGF plays a superior role in inhibiting inflammation in weak acidic wounds.

Keywords: fibroblast growth factor; inflammation; microenvironment; pH value; wound healing.

Grants and funding

This work was financially supported by the Military Medical Innovation Special Projects(Grant Nos.18CXZ029 to BC), the Shanghai Wang Zhengguo Trauma Medicine Development Foundation(Grant Nos. SZYZTR04 to BC), the National Natural Science Foundation of China (Grant Nos. 82102334 to SC), the Key Foundation of Zhejiang Provincial Natural Science Foundation (Grant Nos. LZ22C100001 to SC), Startup Funding of Wenzhou Institute, University of Chinese Academy of Sciences (Grant No. WIUCASQD2021026 to SC).