Matrix metalloproteinases (MMPs) are enzymes that can degrade collagen in hybrid layer and reduce the longevity of adhesive restorations. As scientific understanding of the MMPs has advanced, useful strategies focusing on preventing these enzymes' actions by MMP inhibitors have quickly developed in many medical fields. However, in restorative dentistry, it is still not well established. This paper is an overview of the strategies to inhibit MMPs that can achieve a long-lasting material-tooth adhesion. Literature search was performed comprehensively using the electronic databases: PubMed, ScienceDirect and Scopus including articles from May 2007 to December 2019 and the main search terms were “matrix metalloproteinases”, “collagen”, and “dentin” and “hybrid layer”. MMPs typical structure consists of several distinct domains. MMP inhibitors can be divided into 2 main groups: synthetic (synthetic-peptides, non-peptide molecules and compounds, tetracyclines, metallic ions, and others) and natural bioactive inhibitors mainly flavonoids. Selective inhibitors of MMPs promise to be the future for specific targeting of preventing dentin proteolysis. The knowledge about MMPs functionality should be considered to synthesize drugs capable to efficiently and selectively block MMPs chemical routes targeting their inactivation in order to overcome the current limitations of the therapeutic use of MMPs inhibitors, i.e., easy clinical application and long-lasting effect.

Citations

Citations to this article as recorded by  

• Exploring the effectiveness of doxycycline in restorative dentistry: a systematic review of in vitro studies
  Bruna Tavares Carneiro, Marina Minici Dumont Prado, Iara de Oliveira Nogueira, Allyson Nogueira Moreira, Carolina Bosso André
  Odontology.2025; 113(1): 15.     CrossRef
• Multifunctional Dual Enzyme-Responsive Nanostructured Lipid Carriers for Targeting and Enhancing the Treatment of Bacterial Infections
  Kerisha Chetty, Xylia Q. Peters, Calvin A. Omolo, Eman A. Ismail, Mohammed A. Gafar, Eman Elhassan, Sania Z. F. Kassam, Jasoda Govender, Sbongumusa Dlamini, Thirumala Govender
  ACS Applied Bio Materials.2025; 8(1): 548.     CrossRef
• Impact of silver diamine fluoride on composite resin bond strength: An In vitro study with various adhesive systems
  Farzaneh Shirani, Shirin Ravanbod, Mohammad Soroush Sehat
  Heliyon.2025; 11(2): e41731.     CrossRef
• Riboflavin-Mediated Photodynamic Therapy in Periodontology: A Systematic Review of Applications and Outcomes
  Jakub Fiegler-Rudol, Maciej Łopaciński, Artur Los, Dariusz Skaba, Rafał Wiench
  Pharmaceutics.2025; 17(2): 217.     CrossRef
• Evolution of Dental Resin Adhesives—A Comprehensive Review
  Waad Khalid Alomran, Mohammed Zahedul Islam Nizami, Hockin H. K. Xu, Jirun Sun
  Journal of Functional Biomaterials.2025; 16(3): 104.     CrossRef
• Long-term hybrid stability and matrix metalloproteinase inhibition by fucosterol in resin-dentin bonding biomechanics
  Hyeryeong Kim, Yu-Jung Jung, Yeon Kim, Moon-Kyoung Bae, Kyung-Hyeon Yoo, Seog-Young Yoon, Hae Ryoun Park, In-Ryoung Kim, Yong-Il Kim
  Scientific Reports.2024;[Epub]     CrossRef
• Multifunctional Dental Adhesives Formulated with Silane-Coated Magnetic Fe3O4@m-SiO2 Core–Shell Particles to Counteract Adhesive Interfacial Breakdown
  Lamia Sami Mokeem, Isadora Martini Garcia, Abdulrahman A. Balhaddad, Yucheng Lan, Dereje Seifu, Michael D. Weir, Mary Anne Melo
  ACS Applied Materials & Interfaces.2024; 16(2): 2120.     CrossRef
• Improving the Push-Out Bond Strength of Fiber Posts in Diabetic Dentin: The Role of Chlorexidine Irrigation and Resin Cements
  Beyza Arslandaş Dinçtürk, Arzu Şahin Mantı, Cemile Kedici Alp, Ayşenur Altuğ Yıldırım, Arzu Kaya Mumcu
  Journal of Functional Biomaterials.2024; 16(1): 4.     CrossRef
• Serum levels of matrix metalloproteinases 1, 2, and 7, and their tissue inhibitors 1, 2, 3, and 4 in polytraumatized patients: Time trajectories, correlations, and their ability to predict mortality
  Lukas L. Negrin, Greta L. Carlin, Robin Ristl, Stefan Hajdu, Andre van Wijnen
  PLOS ONE.2024; 19(3): e0300258.     CrossRef
• Current approaches to produce durable biomaterials: Trends in polymeric materials for restorative dentistry applications
  Carmem S. Pfeifer, Fernanda S. Lucena, Matthew G. Logan, Devatha Nair, Steven H. Lewis
  Dental Materials.2024; 40(12): 2122.     CrossRef
• Effect of Different MMP Inhibitors on the Bond Strength and Durability of an Etch-and-rinse and a Self-etch Adhesive
  Ahmet Hazar, Mine Betül Üçtaşlı
  ADO Klinik Bilimler Dergisi.2024; 13(3): 453.     CrossRef
• Matrix metalloproteinases in dentin: Assessing their presence, activity, and inhibitors – a review of current trends
  Lavanya Anumula, Sindhu Ramesh, Venkata Suneel Kumar Kolaparthi
  Dental Materials.2024; 40(11): 2051.     CrossRef
• Effect of nonthermal atmospheric plasma application at different time intervals on the dentinal shear bond strength pretreated with 2% chlorhexidine as cavity disinfectant: An in vitro study
  Roopadevi Garlapati, Nagesh Bolla, Gali Praveen Kumar, Mayana Aameena Banu, Bandlapally Sreenivasa Guptha Anila, Shaik Afreen Kamal
  Journal of Conservative Dentistry and Endodontics.2024; 27(7): 769.     CrossRef
• Effect of MMP Inhibitors on Shear Bond Strength of Adhesive to Dentin after Different Drying Techniques: An In-Vitro Study
  Sheethal K. Narayanan, Krishnan Hari, Joy Mathew, Anila Sukumaran, Basil Joy, Joel Mathew
  Journal of Pharmacy and Bioallied Sciences.2024; 16(Suppl 5): S4639.     CrossRef
• In situ detection of endogenous proteolytic activity and the effect of inhibitors on tooth root surface
  Izumi Sakurai, Gen Mayanagi, Satoru Yamada, Nobuhiro Takahashi
  Journal of Dentistry.2023; 131: 104471.     CrossRef
• Effects of Cathepsin K Inhibitors on Dentin Erosion: An in vitro Study
  Yi-ying Chen, Xiu-jiao Lin, Zhi-cen Lu, Annette Wiegand, Hao Yu
  Caries Research.2023; 57(2): 159.     CrossRef
• The Role of Duration of Chlorhexidine Gluconate 2% Application on the Shear Bond Strength of a Total Etch Bonding Agent: A Comparative Study
  Azmi Fasya, Yolanda Yolanda, Ayu Trisna Hayati
  Clinical, Cosmetic and Investigational Dentistry.2023; Volume 15: 281.     CrossRef
• The effect of kaempferol on the dentin bonding stability through matrix metalloproteinases inhibition and collagen crosslink in dentin biomodification
  Jeonghwa Cho, Hyeryeong Kim, Kyung-Hyeon Yoo, Youna Paik, In-Ryoung Kim, Seog-Young Yoon, Yong-Il Kim
  Journal of Dental Sciences.2023; 18(3): 1023.     CrossRef
• EFFECT OF TiO2 DECORATED CELLULOSIC MATERIALS ADDITION ON MECHANICAL AND BIOLOGICAL PROPERTIES OF DENTAL ADHESIVE COMPOSITES
  HUMAIRA JABEEN, NAWSHAD MUHAMMAD, USAMA SIDDIQUI, MUHAMMAD SABIR, NAVEED AHMAD, SAAD LIAQAT
  Cellulose Chemistry and Technology.2023; 57(5-6): 541.     CrossRef
• Insight into the development of versatile dentin bonding agents to increase the durability of the bonding interface
  Isabel Cristina Celerino de Moraes Porto, Teresa de Lisieux Guedes Ferreira Lôbo, Raphaela Farias Rodrigues, Rodrigo Barros Esteves Lins, Marcos Aurélio Bomfim da Silva
  Frontiers in Dental Medicine.2023;[Epub]     CrossRef
• Current Strategies to Control Recurrent and Residual Caries with Resin Composite Restorations: Operator- and Material-Related Factors
  Moataz Elgezawi, Rasha Haridy, Moamen A. Abdalla, Katrin Heck, Miriam Draenert, Dalia Kaisarly
  Journal of Clinical Medicine.2022; 11(21): 6591.     CrossRef
• Adhesive Strength in Dentin Conditioned with 18% Ethylenediaminetetraacetic Acid versus 35% Phosphoric Acid: In Vitro Study with 1-Year Artificial Aging
  Esther Alcántara-Obispo, Flor Santander-Rengifo, Marysela Ladera-Castañeda, Carlos López-Gurreonero, Antonieta Castro Pérez-Vargas, Alberto Cornejo-Pinto, Luis Cervantes-Ganoza, César Cayo-Rojas
  Polymers.2022; 14(20): 4291.     CrossRef
• Effects of the Combined Application of Trimethylated Chitosan and Carbodiimide on the Biostability and Antibacterial Activity of Dentin Collagen Matrix
  Xiangyao Wang, Qilin Li, Haibo Lu, Zhuo Liu, Yaxin Wu, Jing Mao, Shiqiang Gong
  Polymers.2022; 14(15): 3166.     CrossRef
• Matrix Metalloproteinases in Dental and Periodontal Tissues and Their Current Inhibitors: Developmental, Degradational and Pathological Aspects
  Moataz Elgezawi, Rasha Haridy, Khalid Almas, Moamen A. Abdalla, Omar Omar, Hatem Abuohashish, Abeer Elembaby, Uta Christine Wölfle, Yasir Siddiqui, Dalia Kaisarly
  International Journal of Molecular Sciences.2022; 23(16): 8929.     CrossRef
• Mussel-inspired monomer – A new selective protease inhibitor against dentine collagen degradation
  Kang Li, Fung Man Ngo, Angela Yat Laam Yau, Winnie Wai Ling Tam, Edmund Chun Ming Tse, James Kit Hon Tsoi, Cynthia Kar Yung Yiu
  Dental Materials.2022; 38(7): 1149.     CrossRef
• Effect of Collagen Crosslinkers on Dentin Bond Strength of Adhesive Systems: A Systematic Review and Meta-Analysis
  Louis Hardan, Umer Daood, Rim Bourgi, Carlos Enrique Cuevas-Suárez, Walter Devoto, Maciej Zarow, Natalia Jakubowicz, Juan Eliezer Zamarripa-Calderón, Mateusz Radwanski, Giovana Orsini, Monika Lukomska-Szymanska
  Cells.2022; 11(15): 2417.     CrossRef
• Marginal Integrity of Composite Restoration with and without Surface Pretreatment by Gold and Silver Nanoparticles vs Chlorhexidine: A Randomized Controlled Trial
  Aya AEM Nemt-Allah, Shereen H Ibrahim, Amira F El-Zoghby
  The Journal of Contemporary Dental Practice.2022; 22(10): 1087.     CrossRef
• Use of the adhesive layer as a controlled release platform for doxycycline, as promising advancement for longer durability of dentin adhesion
  Lívia Rodrigues de Menezes, Dayane Carvalho Ramos Salles de Oliveira, Cássia Almeida Brito, Emerson Oliveira da Silva
  International Journal of Adhesion and Adhesives.2021; 108: 102889.     CrossRef
• Understanding collagen interactions and their targeted regulation by novel drugs
  Marialucia Gallorini, Simone Carradori
  Expert Opinion on Drug Discovery.2021; 16(11): 1239.     CrossRef
• Effect of Curcumin Suspension and Vitamin C on Dentin Shear Bond Strength and Durability. A Pilot Study
  Dalia A. Abuelenain, Ensanya A. Abou Neel, Tariq S. Abuhaimed, Amal M. Alamri, Hanan S. Ammar, Sahar M. N. Bukhary
  The Open Dentistry Journal.2021; 15(1): 540.     CrossRef
• Reinforced Universal Adhesive by Ribose Crosslinker: A Novel Strategy in Adhesive Dentistry
  Rim Bourgi, Umer Daood, Mohammed Nadeem Bijle, Amr Fawzy, Maroun Ghaleb, Louis Hardan
  Polymers.2021; 13(5): 704.     CrossRef