Approaching the compressive modulus of articular cartilage with a decellularized cartilage-based hydrogel
Open accessAbstract
Unlabelled ECM-based materials are appealing for tissue engineering strategies because they may promote stem cell recruitment, cell infiltration, and cell differentiation without the need to supplement with additional biological factors. Cartilage ECM has recently shown potential to be chondroinductive, particularly in a hydrogel-based system, which may be revolutionary in orthopedic medicine. However, hydrogels composed of natural materials are often mechanically inferior to synthetic materials, which is a major limitation for load-bearing tissue applications. The objective was therefore to create an unprecedented hydrogel derived entirely from native cartilage ECM that was both mechanically more similar to native cartilage tissue and capable of inducing chondrogenesis. Porcine cartilage was decellularized, solubilized, and then methacrylated and UV photocrosslinked to create methacrylated solubilized decellularized cartilage (MeSDCC) gels. Methacrylated gelatin (GelMA) was employed as a control for both biomechanics and bioactivity. Rat bone marrow-derived mesenchymal stem cells were encapsulated in these networks, which were cultured in vitro for 6weeks, where chondrogenic gene expression, the compressive modulus, swelling, and histology were analyzed. One day after crosslinking, the elastic compressive modulus of the 20% MeSDCC gels was 1070±150kPa. Most notably, the stress strain profile of the 20% MeSDCC gels fell within the 95% confidence interval range of native porcine cartilage. Additionally, MeSDCC gels significantly upregulated chondrogenic genes compared to GelMA as early as day 1 and supported extensive matrix synthesis as observed histologically. Given that these gels approached the mechanics of native cartilage tissue, supported matrix synthesis, and induced chondrogenic gene expression, MeSDCC hydrogels may be promising materials for cartilage tissue engineering applications. Future efforts will focus on improving fracture mechanics as well to benefit overall biomechanical performance.Statement of significance Extracellular matrix (ECM)-based materials are appealing for tissue engineering strategies because they may promote stem cell recruitment, cell infiltration, and cell differentiation without the need to supplement with additional biological factors. One such ECM-based material, cartilage ECM, has recently shown potential to be chondroinductive; however, hydrogels composed of natural materials are often mechanically inferior to synthetic materials, which is a major limitation for load-bearing tissue applications. Therefore, this work is significant because we were the first to create hydrogels derived entirely from cartilage ECM that had mechanical properties similar to that of native cartilage until hydrogel failure. Furthermore, these hydrogels had a compressive modulus of 1070±150kPa, they were chondroinductive, and they supported extensive matrix synthesis. In the current study, we have shown that these new hydrogels may prove to be a promising biomaterial for cartilage tissue engineering applications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Hunziker, E. B. (2002) · Osteoarthritis and Cartilage · doi:10.1053/joca.2002.0801 · Cited by 1,983 · see citing works
Schuurman, W., Levett, P. A., Pot, M. W., van Weeren, P. R., Dhert, W. J. A., Hutmacher, D. W., Melchels, F. P. W., Klein, T. J., & Malda, J. (2013) · Macromolecular Bioscience · doi:10.1002/mabi.201200471 · Cited by 791 · see citing works
Armstrong, C., & Mow, V. C. (1982) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-198264010-00013 · Cited by 776 · see citing works
Extracellular matrix scaffolds for cartilage and bone regeneration
Benders, K. E. M., van Weeren, P. R., Badylak, S. F., Saris, D. B. F., Dhert, W. J. A., & Malda, J. (2013) · Trends in biotechnology · doi:10.1016/j.tibtech.2012.12.004 · Cited by 539 · see citing works
Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix
Freytes, D. O., Martin, J. D., Velankar, S., Lee, A. S., & Badylak, S. F. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2007.12.014 · Cited by 531 · see citing works
Mechanical Properties of Natural Cartilage and Tissue-Engineered Constructs
Little, C. J., Bawolin, N. K., & Chen, D. (2011) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2010.0572 · Cited by 313 · see citing works
The Potential of Human Allogeneic Juvenile Chondrocytes for Restoration of Articular Cartilage
Adkisson, H. D., Martin, J. A., Amendola, R. L., et al. (2010) · The American Journal of Sports Medicine · doi:10.1177/0363546510361950 · Cited by 260 · see citing works
The Impact of Osteoarthritis in the United States
Murphy, L. B., & Helmick, C. G. (2012) · AJN American Journal of Nursing · doi:10.1097/01.naj.0000412646.80054.21 · Cited by 252 · see citing works
Decellularized Cartilage Matrix as a Novel Biomatrix for Cartilage Tissue-Engineering Applications
Schwarz, S., Körber, L., Elsaesser, A. F., Goldberg‐Bockhorn, E., Seitz, A. M., Dürselen, L., Ignatius, A. A., Walther, P., Breiter, R., & Rotter, N. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0705 · Cited by 243 · see citing works
Huang, C.-Y. C., Stankiewicz, A., Ateshian, G. A., et al. (2004) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2004.05.006 · Cited by 221 · see citing works
Seif-Naraghi, S. B., Salvatore, M. A., Schup-Magoffin, P. J., Hu, D. P., & Christman, K. L. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0768 · Cited by 202 · see citing works
Brigham, M. D., Bick, A. G., Lo, E., Bendali, A., Burdick, J. A., & Khademhosseini, A. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2008.0441 · Cited by 199 · see citing works
Rowland, C. R., Lennon, D. P., Caplan, A. I., & Guilak, F. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.027 · Cited by 190 · see citing works
Seif-Naraghi, S. B., Horn, D., Schup-Magoffin, P. J., & Christman, K. L. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2012.06.030 · Cited by 187 · see citing works
The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration
Sutherland, A. J., Converse, G. L., Hopkins, R. A., & Detamore, M. S. (2014) · Advanced Healthcare Materials · doi:10.1002/adhm.201400165 · Cited by 180 · see citing works
Self-citationDeKosky, B. J., Dormer, N. H., Ingavle, G. C., et al. (2010) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2009.0761 · Cited by 160 · see citing works
Advances in skeletal tissue engineering with hydrogels
Elisseeff, J. H., Puleo, C., Yang, F., & Sharma, B. (2005) · Orthodontics and Craniofacial Research · doi:10.1111/j.1601-6343.2005.00335.x · Cited by 151 · see citing works
Kheir, E., Stapleton, T. W., Shaw, D., Jin, Z. M., Fisher, J., & Ingham, E. (2011) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.33171 · Cited by 150 · see citing works
Acellular Biomaterials: An Evolving Alternative to Cell-Based Therapies
Burdick, J. A., Mauck, R. L., Gorman, J. H., & Gorman, R. C. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3003997 · Cited by 139 · see citing works
Fabrication and Repair of Cartilage Defects with a Novel Acellular Cartilage Matrix Scaffold
Yang, Z., Shi, Y., Wei, X., He, J., Yang, S., Dickson, G. R., Tang, J., Xiang, J., Song, C., & Li, G. (2009) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2009.0444 · Cited by 136 · see citing works
Crosslinkable Hydrogels Derived from Cartilage, Meniscus, and Tendon Tissue
Visser, J., Levett, P. A., Moller, N. C. R. T., Besems, J., Boere, K. W. M., van Rijen, M. H. P., de Grauw, J. C., Dhert, W. J. A., van Weeren, P. R., & Malda, J. (2015) · Tissue Engineering Part A · doi:10.1089/ten.tea.2014.0362 · Cited by 114 · see citing works
Electrospun cartilage-derived matrix scaffolds for cartilage tissue engineering
Garrigues, N. W., Little, D., Sanchez‐Adams, J., Ruch, D. S., & Guilak, F. (2013) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35068 · Cited by 112 · see citing works
Cheng, N., Estes, B. T., Young, T., & Guilak, F. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0384 · Cited by 106 · see citing works
Gershlak, J. R., Resnikoff, J., Sullivan, K. E., Williams, C., Wang, R. M., & Black, L. D. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.08.074 · Cited by 85 · see citing works
Schwarz, S., Elsaesser, A. F., Koerber, L., et al. (2012) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.1650 · Cited by 84 · see citing works
Villanueva, I., Weigel, C. A., & Bryant, S. J. (2009) · Acta Biomaterialia · doi:10.1016/j.actbio.2009.05.039 · Cited by 83 · see citing works
Engineered Cartilage Using Primary Chondrocytes Cultured in a Porous Cartilage-Derived Matrix
Cheng, N., Estes, B. T., Young, T., & Guilak, F. (2010) · Regenerative Medicine · doi:10.2217/rme.10.87 · Cited by 82 · see citing works
Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine
Renth, A. N., & Detamore, M. S. (2012) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0080 · Cited by 79 · see citing works
Self-citationMechanical Testing of Hydrogels in Cartilage Tissue Engineering: Beyond the Compressive Modulus
Xiao, Y., Friis, E. A., Gehrke, S. H., & Detamore, M. S. (2013) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0461 · Cited by 78 · see citing works
Self-citation(2015) · Thieme eBooks · doi:10.1055/b-0035-122012 · Cited by 71 · see citing works
Cell-Derived Matrix Coatings for Polymeric Scaffolds
Decaris, M. L., Binder, B. Y. K., Soicher, M. A., et al. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0677 · Cited by 63 · see citing works
Injectable extracellular matrix hydrogel developed using porcine articular cartilage
Kwon, J. S., Yoon, S. M., Shim, S. W., Park, J. H., Min, K. J., Oh, H. J., Kim, J. H., Kim, Y. J., Yoon, J. J., Choi, B. H., et al. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.06.023 · Cited by 63 · see citing works
Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic Approaches
Tatman, P. D., Gerull, W. D., Sweeney-Easter, S., Davis, J. I., Gee, A. O., & Kim, D. (2015) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2015.0142 · Cited by 53 · see citing works
Levorson, E. J., Hu, O., Mountziaris, P. M., et al. (2013) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2013.0288 · Cited by 46 · see citing works
Cha, M. H., Hee, S., Park, G. R., et al. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0358 · Cited by 45 · see citing works
Converse, G. L., Armstrong, M., Quinn, R. W., et al. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2012.03.047 · Cited by 43 · see citing works
A Road Map to Commercialization of Cartilage Therapy in the United States of America
Sridharan, B., Sharma, B., & Detamore, M. S. (2015) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2015.0147 · Cited by 31 · see citing works
Self-citationKhanlari, A., Detamore, M. S., & Gehrke, S. H. (2013) · Macromolecules · doi:10.1021/ma401838h · Cited by 30 · see citing works
Self-citationBeck, E. C., Lohman, B. L., Tabakh, D. B., et al. (2015) · Annals of Biomedical Engineering · doi:10.1007/s10439-015-1277-8 · Cited by 28 · see citing works
Self-citationBIOS Instant Notes in Molecular Biology
McLennan, A. G., Bates, A., Turner, P., et al. (2012) · Taylor & Francis eBooks · doi:10.4324/9780203079508 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [2]Athanasiou KAD Eric M DuRaine Grayson D Hu Jerry C Hari Reddi A Articular Cartilage Boca Raton, FL CRC Press 2013
- [10]Weiss P Fatimi A Guicheux J Vinatier C Hydrogels for Cartilage Tissue Engineering Biomedical Applications of Hydrogels Handbook Springer 2010 247 68
Cited by
Sorted by citations
Lu, S., Cuzzucoli, F., Jiang, J., Liang, L.-G., Wang, Y., Kong, M., Zhao, X., Cui, W., Li, J., & Wang, S. (2018) · Lab on a Chip · doi:10.1039/c8lc00852c · Cited by 144 · see citing works
Wang, Y., Wu, D., Wu, G., Wu, J., Lu, S., Lo, J., He, Y., Zhao, C., Zhao, X., Zhang, H., et al. (2020) · Theranostics · doi:10.7150/thno.38736 · Cited by 93 · see citing works
Tan, X. H., Liu, L., Mitryashkin, A., Wang, Y., & Goh, J. C. H. (2022) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.2c00313 · Cited by 36 · see citing works
Bioprinting of hepatic tissue model using photocrosslinkable dECM-containing composite hydrogel
Tabatabaei Rezaei, N., Kumar, H., Liu, H., Rajeev, A., Natale, G., Lee, S. S., Park, S. S., & Kim, K. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101824 · Cited by 13 · see citing works
Faculty of Medicine and Health Technology, F.-3. T. U., Pitkänen, S., Paakinaho, K., Pihlman, H., Ahola, N., Hannula, M., Asikainen, S., Manninen, M., Morelius, M., Keränen, P., et al. (2019) · European Cells and Materials · doi:10.22203/ecm.v038a04 · Cited by 10 · see citing works
- Authors
- Beck, E. C., Barragan, M., Tadros, M. H., Gehrke, S. H., & Detamore, M. S.
- Affiliations
- University of Kansas Medical Center (US)
- University of Kansas (US)
- Rice University (US)
- Corresponding author
- Detamore, Michael S.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 38
- Pages
- 94-105
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC4903909
- OpenAlex
- W2340116897
- Cited by
- 222
- References
- 42
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 24 · 2023: 23 · 2022: 41 · 2021: 19 · 2020: 21 · 2019: 17 · 2018: 13 · 2017: 11 · 2016: 2
- FWCI
- 15.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01 DE022472, S10 RR024664)
- Major Research Instrumentation (0320648)
- Kansas Bioscience Authority Rising Star Award
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- decellularized cartilage, cartilage matrix, hydrogels, compressive modulus, chondrogenesis, porcine cartilage, bone marrow-derived mesenchymal stem cells, gelatin methacryloyl, stress-strain behavior, cartilage tissue engineering, chondroinduction, mechanical properties of cartilage
- MeSH terms
- Animals, Cartilage, Articular, Extracellular Matrix, Male, Swine, Rats, Sprague-Dawley, Hydrogels, Rats, Mesenchymal Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
