2. Academic Validation
  3. Triple-Tailored Analgesic Hydrogel System Targeting ADAM17 in Orofacial Inflammatory Pain

Triple-Tailored Analgesic Hydrogel System Targeting ADAM17 in Orofacial Inflammatory Pain

  • Adv Healthc Mater. 2025 Jul 16:e2501440. doi: 10.1002/adhm.202501440.
Yingyu Yi 1,  Yuxuan Wu 2,  Yanghong Xu 3,  Zhengjie Han 4,  Yuzhuo Wang 4,  Jianwen Gong 3 5 6,  Yubin Hu 4,  Xinzhao Mai 4,  Weizhe Sheng 4,  Junting Li 4,  Yujie Chen 2,  Zhi Yang 7,  Yaqin Zhu 1
Affiliations

Affiliations

  • 1 Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, 200011, Shanghai, China.
  • 2 State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, 200240, Shanghai, China.
  • 3 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031, Shanghai, China.
  • 4 Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, 200011, Shanghai, China.
  • 5 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 6 School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
  • 7 Department of Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University, 200011, Shanghai, China.
PMID: 40671384 DOI: 10.1002/adhm.202501440
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.

Keywords

ADAM17; hydrogels; nanoparticles; orofacial inflammatory pain.

Figures
Products