ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1660821
This article is part of the Research TopicNanobiotechnology-Driven Strategies for Soft Tissue Repair: Integrating Nano-biomaterials, Stem Cells, and Nanomedicine Delivery SystemsView all articles
Injectable Cinnamaldehyde–Loaded ZIF-8/Gallic Acid–Grafted Gelatin Hydrogel for Enhanced Angiogenesis and Skin Regeneration in Diabetic Wound Healing
Provisionally accepted
Bo Zhou1Chen Zhang2Sheng Dai3Jin Zhao1Hauiyu Li3Yanbin Peng1Yunfeng Chu1Zhong Chen1
Haotian Qin1*
Zeng Hui1*- 1Peking University Shenzhen Hospital, Shenzhen, China
- 2Hubei University of Medicine, Shiyan, China
- 3Southwest Jiaotong University, Chengdu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Chronic diabetic wounds remain a major clinical challenge due to persistent ischemia, oxidative stress, and impaired angiogenesis. Injectable hydrogels capable of adapting to irregular wound beds and delivering bioactive cues offer promising therapeutic potential for enhancing tissue regeneration. Methods: We developed a multifunctional injectable hydrogel by incorporating cinnamaldehyde-loaded ZIF-8 nanoparticles (CA@ZIF-8) into a gallic acid–grafted gelatin (GGA) matrix, followed by transglutaminase-mediated crosslinking. The physicochemical characteristics, drug release behavior, and mechanical performance of the CA@ZIF-8/GGA hydrogel were systematically evaluated. In vitro assays using human umbilical vein endothelial cells (HUVECs) were conducted to assess cytocompatibility and angiogenic activity. A full-thickness skin wound model in streptozotocin-induced diabetic rats was employed to evaluate in vivo wound healing efficacy and biocompatibility. Results: The CA@ZIF-8/GGA hydrogel exhibited favorable injectability, enhanced mechanical strength, and sustained release of both cinnamaldehyde and Zn²⁺. In vitro, the hydrogel significantly promoted HUVEC proliferation, migration, and tube formation, accompanied by upregulated expression of CD31 and VEGF. In vivo, CA(0.6)@ZIF-8/GGA-treated wounds demonstrated accelerated closure, enhanced granulation tissue
Keywords: Diabetic wound healing model, Injectable hydrogel, Cinnamaldehyde, ZIF-8 nanoparticles, Angiogenesis, MOF-based delivery system
Received: 06 Jul 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Zhou, Zhang, Dai, Zhao, Li, Peng, Chu, Chen, Qin and Hui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Haotian Qin, Peking University Shenzhen Hospital, Shenzhen, China
Zeng Hui, Peking University Shenzhen Hospital, Shenzhen, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.