Bo Zhou, Chen Zhang, Sheng Dai, Jin Zhao, Huaiyu Li, Yanbin Peng, Yunfeng Chu, Zhong Chen, Haotian Qin, Hui Zeng
{"title":"可注射肉桂醛负载ZIF-8/没食子酸的明胶水凝胶在糖尿病伤口愈合中促进血管生成和皮肤再生。","authors":"Bo Zhou, Chen Zhang, Sheng Dai, Jin Zhao, Huaiyu Li, Yanbin Peng, Yunfeng Chu, Zhong Chen, Haotian Qin, Hui Zeng","doi":"10.3389/fbioe.2025.1660821","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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. <i>In vitro</i> 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 <i>in vivo</i> wound healing efficacy and biocompatibility.</p><p><strong>Results: </strong>The CA@ZIF-8/GGA hydrogel exhibited favorable injectability, enhanced mechanical strength, and sustained release of both cinnamaldehyde and Zn<sup>2+</sup>. <i>In vitro</i>, the hydrogel significantly promoted HUVEC proliferation, migration, and tube formation, accompanied by upregulated expression of CD31 and VEGF. <i>In vivo</i>, CA(0.6)@ZIF-8/GGA-treated wounds demonstrated accelerated closure, enhanced granulation tissue formation, increased neovascularization, and re-epithelialization compared with control groups. No histological abnormalities were observed in major organs, indicating good systemic biocompatibility.</p><p><strong>Conclusion: </strong>This study presents an injectable CA@ZIF-8/GGA composite hydrogel that effectively promotes angiogenesis and diabetic wound regeneration. The synergistic integration of MOF-based controlled release and polyphenol-enhanced bioactivity highlights its potential as a clinically translatable platform for chronic wound management.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1660821"},"PeriodicalIF":4.8000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460342/pdf/","citationCount":"0","resultStr":"{\"title\":\"Injectable cinnamaldehyde-loaded ZIF-8/Gallic Acid-Grafted gelatin hydrogel for enhanced angiogenesis and skin regeneration in diabetic wound healing.\",\"authors\":\"Bo Zhou, Chen Zhang, Sheng Dai, Jin Zhao, Huaiyu Li, Yanbin Peng, Yunfeng Chu, Zhong Chen, Haotian Qin, Hui Zeng\",\"doi\":\"10.3389/fbioe.2025.1660821\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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. <i>In vitro</i> 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 <i>in vivo</i> wound healing efficacy and biocompatibility.</p><p><strong>Results: </strong>The CA@ZIF-8/GGA hydrogel exhibited favorable injectability, enhanced mechanical strength, and sustained release of both cinnamaldehyde and Zn<sup>2+</sup>. <i>In vitro</i>, the hydrogel significantly promoted HUVEC proliferation, migration, and tube formation, accompanied by upregulated expression of CD31 and VEGF. <i>In vivo</i>, CA(0.6)@ZIF-8/GGA-treated wounds demonstrated accelerated closure, enhanced granulation tissue formation, increased neovascularization, and re-epithelialization compared with control groups. No histological abnormalities were observed in major organs, indicating good systemic biocompatibility.</p><p><strong>Conclusion: </strong>This study presents an injectable CA@ZIF-8/GGA composite hydrogel that effectively promotes angiogenesis and diabetic wound regeneration. The synergistic integration of MOF-based controlled release and polyphenol-enhanced bioactivity highlights its potential as a clinically translatable platform for chronic wound management.</p>\",\"PeriodicalId\":12444,\"journal\":{\"name\":\"Frontiers in Bioengineering and Biotechnology\",\"volume\":\"13 \",\"pages\":\"1660821\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12460342/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Bioengineering and Biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.3389/fbioe.2025.1660821\",\"RegionNum\":3,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Bioengineering and Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.3389/fbioe.2025.1660821","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Injectable cinnamaldehyde-loaded ZIF-8/Gallic Acid-Grafted gelatin hydrogel for enhanced angiogenesis and skin regeneration in diabetic wound healing.
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 formation, increased neovascularization, and re-epithelialization compared with control groups. No histological abnormalities were observed in major organs, indicating good systemic biocompatibility.
Conclusion: This study presents an injectable CA@ZIF-8/GGA composite hydrogel that effectively promotes angiogenesis and diabetic wound regeneration. The synergistic integration of MOF-based controlled release and polyphenol-enhanced bioactivity highlights its potential as a clinically translatable platform for chronic wound management.
期刊介绍：
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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