{"title":"Triple-Tailored Analgesic Hydrogel System Targeting ADAM17 in Orofacial Inflammatory Pain.","authors":"Yingyu Yi, Yuxuan Wu, Yanghong Xu, Zhengjie Han, Yuzhuo Wang, Jianwen Gong, Yubin Hu, Xinzhao Mai, Weizhe Sheng, Junting Li, Yujie Chen, Zhi Yang, Yaqin Zhu","doi":"10.1002/adhm.202501440","DOIUrl":null,"url":null,"abstract":"<p><p>Orofacial inflammatory pain (OFP) is challenging to manage due to its high incidence, complex anatomy, and multifactorial etiology. To address this, a three-step customized therapeutic system is proposed for prolonged pain relief and efficient local drug delivery. First, ADAM17 is identified as a novel therapeutic target for OFP, and find a small-molecule inhibitor, TAPI-1, which can effectively suppress ADAM17 activity. Subsequently, guided by the presence of an amine group on TAPI-1, an optimized hydrogel matrix is synthesized via Schiff-base bonding to enable stable encapsulation. The hydrogel, composed of hyaluronic acid derivatives carrying aldehyde (HAALD) and aminated gelatin (AGel), forms a scaffold that slows drug release. Second, for clinical application in orofacial tissue, unmodified hyaluronic acid (HA) and gelatin are incorporated to optimize the hydrogel's rheological properties for practicable injection. Third, to further prolong drug release, customized hollow mesoporous silica nanoparticles are added to trap a portion of TAPI-1, matching the drug's molecular diameter. This triple-tailored sustained-release hydrogel (HHGA hydrogel) maintains effective drug levels for 7 days, aligning with the pain phase and obviously relieving pain in mice. This \"drug-device\" innovation exemplifies the potential of personalized medicine in pain management and targeted therapies in translational medicine.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e2501440"},"PeriodicalIF":10.0000,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Healthcare Materials","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1002/adhm.202501440","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0
Abstract
Orofacial inflammatory pain (OFP) is challenging to manage due to its high incidence, complex anatomy, and multifactorial etiology. To address this, a three-step customized therapeutic system is proposed for prolonged pain relief and efficient local drug delivery. First, ADAM17 is identified as a novel therapeutic target for OFP, and find a small-molecule inhibitor, TAPI-1, which can effectively suppress ADAM17 activity. Subsequently, guided by the presence of an amine group on TAPI-1, an optimized hydrogel matrix is synthesized via Schiff-base bonding to enable stable encapsulation. The hydrogel, composed of hyaluronic acid derivatives carrying aldehyde (HAALD) and aminated gelatin (AGel), forms a scaffold that slows drug release. Second, for clinical application in orofacial tissue, unmodified hyaluronic acid (HA) and gelatin are incorporated to optimize the hydrogel's rheological properties for practicable injection. Third, to further prolong drug release, customized hollow mesoporous silica nanoparticles are added to trap a portion of TAPI-1, matching the drug's molecular diameter. This triple-tailored sustained-release hydrogel (HHGA hydrogel) maintains effective drug levels for 7 days, aligning with the pain phase and obviously relieving pain in mice. This "drug-device" innovation exemplifies the potential of personalized medicine in pain management and targeted therapies in translational medicine.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.