{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:52:56Z","timestamp":1789588376346,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of North Texas Startup Funding","award":["T32 GM136501"],"award-info":[{"award-number":["T32 GM136501"]}]},{"name":"Center of Functional Materials (CFM) Research Award","award":["T32 GM136501"],"award-info":[{"award-number":["T32 GM136501"]}]},{"name":"UNT Graduate Student Research Award","award":["T32 GM136501"],"award-info":[{"award-number":["T32 GM136501"]}]},{"name":"NIH G-RISE Program at the University of North Texas","award":["T32 GM136501"],"award-info":[{"award-number":["T32 GM136501"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Osteoarthritis (OA) is a chronic joint disease characterized by irreversible cartilage degradation. Current clinical treatment options lack effective pharmaceutical interventions targeting the disease\u2019s root causes. MMP (matrix metalloproteinase) inhibitors represent a new approach to slowing OA progression by addressing cartilage degradation mechanisms. However, very few drugs within this class are in preclinical or clinical trial phases. Hydrogel-based 3D in vitro models have shown promise as preclinical testing platforms due to their resemblance to native extracellular matrix (ECM), abundant availability, and ease of use. Metalloproteinase-13 (MMP-13) is thought to be a major contributor to the degradation of articular cartilage in OA by aggressively breaking down type II collagen. This study focused on testing MMP-13 inhibitors using a GelMA-alginate hydrogel-based OA model induced by cytokines interleukin-1 beta (IL-1\u03b2) and tumor necrosis factor alpha (TNF-\u03b1). The results demonstrate a significant inhibition of type II collagen breakdown by measuring C2C concentration using ELISA after treatment with MMP-13 inhibitors. However, inconsistencies in human cartilage explant samples led to inconclusive results. Nonetheless, the study highlights the GelMA-alginate hydrogel-based OA model as an alternative to human-sourced cartilage explants for in vitro drug screening.<\/jats:p>","DOI":"10.3390\/polym16111572","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T03:51:45Z","timestamp":1717386705000},"page":"1572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Screening of MMP-13 Inhibitors Using a GelMA-Alginate Interpenetrating Network Hydrogel-Based Model Mimicking Cytokine-Induced Key Features of Osteoarthritis In Vitro"],"prefix":"10.3390","volume":"16","author":[{"given":"Qichan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of North Texas, Denton, TX 76203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1253-3033","authenticated-orcid":false,"given":"Steven L.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Palladino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of North Texas, Denton, TX 76203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0603-6683","authenticated-orcid":false,"given":"Melanie","family":"Ecker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of North Texas, Denton, TX 76203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00264-013-2088-x","article-title":"Osteoarthritis: Genes, Nature-Nurture Interaction and the Role of Leptin","volume":"37","author":"Garner","year":"2013","journal-title":"Int. Orthop."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/s40674-016-0054-7","article-title":"Knee and Hip Osteoarthritis Management: A Review of Current and Emerging Non-Pharmacological Approaches","volume":"2","author":"Murphy","year":"2016","journal-title":"Curr. Treat. Options Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Song, Z., Li, Y., Shang, C., Shang, G., Kou, H., Li, J., Chen, S., and Liu, H. (2021). Sprifermin: Effects on Cartilage Homeostasis and Therapeutic Prospects in Cartilage-Related Diseases. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.786546"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rodrigues, T.A., Freire, A.O., Bonfim, B.F., Cart\u00e1genes, M.S.S., and Garcia, J.B.S. (2018). Strontium Ranelate as a Possible Disease-Modifying Osteoarthritis Drug: A Systematic Review. Braz. J. Med. Biol. Res., 51.","DOI":"10.1590\/1414-431x20187440"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ginnetti, A.T., Paone, D.V., Nanda, K.K., Li, J., Busuek, M., Johnson, S.A., Lu, J., Soisson, S.M., Robinson, R., and Fisher, J. (2022). Lead Optimization of Cathepsin K Inhibitors for the Treatment of Osteoarthritis. Bioorg. Med. Chem. Lett., 74.","DOI":"10.2139\/ssrn.4144318"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116786","DOI":"10.1016\/j.lfs.2019.116786","article-title":"The Role of Matrix Metalloproteinases in Osteoarthritis Pathogenesis: An Updated Review","volume":"234","author":"Mehana","year":"2019","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hu, Q., and Ecker, M. (2021). Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041742"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1002\/art.24629","article-title":"A New Class of Potent Matrix Metalloproteinase 13 Inhibitors for Potential Treatment of Osteoarthritis: Evidence of Histologic and Clinical Efficacy without Musculoskeletal Toxicity in Rat Models","volume":"60","author":"Baragi","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00011-009-0112-9","article-title":"Novel Selective MMP-13 Inhibitors Reduce Collagen Degradation in Bovine Articular and Human Osteoarthritis Cartilage Explants","volume":"59","author":"Piecha","year":"2009","journal-title":"Inflamm. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bupphathong, S., Quiroz, C., Huang, W., Chung, P.F., Tao, H.Y., and Lin, C.H. (2022). Gelatin Methacrylate Hydrogel for Tissue Engineering Applications\u2014A Review on Material Modifications. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020171"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Abasalizadeh, F., Moghaddam, S.V., Alizadeh, E., Akbari, E., Kashani, E., Fazljou, S.M.B., Torbati, M., and Akbarzadeh, A. (2020). Alginate-Based Hydrogels as Drug Delivery Vehicles in Cancer Treatment and Their Applications in Wound Dressing and 3D Bioprinting. J. Biol. Eng., 14.","DOI":"10.1186\/s13036-020-0227-7"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ma, C., Kim, Y.K., Lee, M.H., and Jang, Y.S. (2023). Development of Gelatin Methacryloyl\/Sodium Alginate Interpenetrating Polymer Network Hydrogels for Bone Regeneration by Activating the Wnt\/\u03b2-Catenin Signaling Pathway via Lithium Release. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713613"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39722","DOI":"10.1039\/D0RA04316H","article-title":"A Sodium Alginate-Based Sustained-Release IPN Hydrogel and Its Applications","volume":"10","author":"Zou","year":"2020","journal-title":"RSC Adv."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hu, Q., Torres, M.A., Pan, H., Williams, S.L., and Ecker, M. (2024). Precision Engineering of Chondrocyte Microenvironments: Investigating the Optimal Reaction Conditions for Type B Gelatin Methacrylate Hydrogel Matrix for TC28a2 Cells. J. Funct. Biomater., 15.","DOI":"10.3390\/jfb15030077"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Saletti, M., Paolino, M., Ballerini, L., Giuliani, G., Leone, G., Lamponi, S., Andreassi, M., Bonechi, C., Donati, A., and Piovani, D. (2022). Click-Chemistry Cross-Linking of Hyaluronan Graft Copolymers. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14051041"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.6061\/clinics\/2012(02)03","article-title":"Characterization of Human Adipose-Derived Stem Cells and Expression of Chondrogenic Genes during Induction of Cartilage Differentiation","volume":"67","author":"Hamid","year":"2012","journal-title":"Clinics"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hu, N., Qian, L., Hu, Y., Shou, J.Z., Wang, C., Giffen, C., Wang, Q.H., Wang, Y., Goldstein, A.M., and Emmert-Buck, M. (2006). Quantitative Real-Time RT-PCR Validation of Differential MRNA Expression of SPARC, FADD, Fascin, COL7A1, CK4, TGM3, ECMI, PPL and EVPL in Esophageal Squamous Cell Carcinoma. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-33"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.1016\/j.joca.2010.05.026","article-title":"Basic Methods in Histopathology of Joint Tissues","volume":"18","author":"Schmitz","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1046\/j.1432-1327.2000.01606.x","article-title":"Investigation of the Alamar Blue (Resazurin) Fluorescent Dye for the Assessment of Mammalian Cell Cytotoxicity","volume":"267","author":"Wilson","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.joca.2015.04.022","article-title":"Type II Collagen C2C Epitope in Human Synovial Fluid and Serum after Knee Injury\u2014Associations with Molecular and Structural Markers of Injury","volume":"23","author":"Kumahashi","year":"2015","journal-title":"Osteoarthr. Cartil."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1016\/S0142-9612(03)00343-0","article-title":"RGD Modified Polymers: Biomaterials for Stimulated Cell Adhesion and Beyond","volume":"24","author":"Hersel","year":"2003","journal-title":"Biomaterials"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sun, M., Sun, X., Wang, Z., Guo, S., Yu, G., and Yang, H. (2018). Synthesis and Properties of Gelatin Methacryloyl (GelMA) Hydrogels and Their Recent Applications in Load-Bearing Tissue. Polymers, 10.","DOI":"10.3390\/polym10111290"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27686","DOI":"10.1080\/19443994.2016.1178178","article-title":"Green Synthesis of Novel Silver Nanocomposite Hydrogel Based on Sodium Alginate as an Efficient Biosorbent for the Dye Wastewater Treatment: Prediction of Isotherm and Kinetic Parameters","volume":"57","year":"2016","journal-title":"Desalin. Water Treat."},{"key":"ref_24","first-page":"316","article-title":"Hydrogel Scaffolds for Tissue Engineering: Progress and Challenges","volume":"2013","author":"Yacoub","year":"2013","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_25","first-page":"37","article-title":"Culture of Immortalized Chondrocytes and Their Use as Models of Chondrocyte Function","volume":"100","author":"Goldring","year":"2004","journal-title":"Methods Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1002\/art.11341","article-title":"Molecular Phenotyping of Human Chondrocyte Cell Lines T\/C-28a2, T\/C-28a4, and C-28\/I2","volume":"48","author":"Finger","year":"2003","journal-title":"Arthritis Rheum."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/11\/1572\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:52:27Z","timestamp":1760107947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/11\/1572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,1]]},"references-count":26,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["polym16111572"],"URL":"https:\/\/doi.org\/10.3390\/polym16111572","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,1]]}}}