Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2023; 15(7): 768-780
Published online Jul 26, 2023. doi: 10.4252/wjsc.v15.i7.768
Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing via creating a fetal-like niche
Guo-Kun Zhang, Jing Ren, Ji-Ping Li, Dong-Xu Wang, Sheng-Nan Wang, Li-Yan Shi, Chun-Yi Li
Guo-Kun Zhang, Jing Ren, Ji-Ping Li, Dong-Xu Wang, Sheng-Nan Wang, Chun-Yi Li, Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130600, Jilin Province, China
Jing Ren, Chun-Yi Li, College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin Province, China
Li-Yan Shi, China-Japan Union Hospital, Jilin University, Changchun 130033, Jilin Province, China
Author contributions: Li CY and Zhang GK designed and supervised the research; Zhang GK, Ren J, and Li JP performed the research and analyzed the data; Wang DX and Zhang GK contributed to animal experiments; Ren J contributed to histopathological experiments; Li JP and Wang SN contributed to cell experiments; Zhang GK, Shi LY, and Li CY wrote and edited the paper; and all authors read and approved the final manuscript.
Supported by the Natural Science Foundation of Jilin Province, No. YDZJ202301ZYTS508; National Natural Science Foundation of China, No. U20A20403; Doctoral Research Start-Up Fund of Changchun Sci-Tech University, No. 202303; Young Scientific and Technological Talents Support Project of Jilin Province, No. QT202203; and Strategic Research and Consulting Project of Chinese Academy of Engineering, No. JL2022-05.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committee of Changchun Sci-Tech University (Approval No. CKARI2020012).
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chun-Yi Li, PhD, Professor, Institute of Antler Science and Product Technology, Changchun Sci-Tech University, No. 1345 Pudong Road, Changchun 130600, Jilin Province, China. lichunyi1959@163.com
Received: April 28, 2023
Peer-review started: April 28, 2023
First decision: June 7, 2023
Revised: June 9, 2023
Accepted: July 11, 2023
Article in press: July 11, 2023
Published online: July 26, 2023
Abstract
BACKGROUND

Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.

AIM

To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing.

METHODS

We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin. Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.

RESULTS

The results showed that HARM accelerated wound healing rate and reduced scar formation. Also, HARM stimulated the regeneration of cutaneous appendages and blood vessels, and reduced collagen fiber aggregation. Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site. The levels of fetal wound healing-related genes, including Collagen III and TGFβ3 treated with HARM were all increased, while the expression levels of Collagen I, TGFβ1, and Engrailed 1 were decreased in the healing. Moreover, the number of stem cells was increased in the fetal-like niche created by HARM, which may contribute to the regeneration of cutaneous appendages.

CONCLUSION

Overall, we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds. We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.

Keywords: Hydrogel, Antler reserve mesenchyme, Regenerative wound healing, Fetal-like niche

Core Tip: Our study developed an injectable hydrogel made from antler reserve mesenchyme (a tissue suitable for stem cells) matrix for the regenerative repair of full-thickness cutaneous wounds. Moreover, we uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.