Control of crosslinking for tailoring collagen-based scaffolds stability and mechanics
Open accessAbstract
We provide evidence to show that the standard reactant concentrations used in tissue engineering to cross-link collagen-based scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against degradation in an aqueous environment. We demonstrate this with a detailed and systematic study by comparing scaffolds made from (a) collagen from two different suppliers, (b) gelatin (a partially denatured collagen) and (c) 50% collagen-50% gelatin mixtures. The materials were processed, using lyophilisation, to produce homogeneous, highly porous scaffolds with isotropic architectures and pore diameters ranging from 130 to 260 μm. Scaffolds were cross-linked using a carbodiimide treatment, to establish the effect of the variations in crosslinking conditions (down to very low concentrations) on the morphology, swelling, degradation and mechanical properties of the scaffolds. Carbodiimide concentration of 11.5mg/ml was defined as the standard (100%) and was progressively diluted down to 0.1%. It was found that 10-fold reduction in the carbodiimide content led to the significant increase (almost 4-fold) in the amount of free amine groups (primarily on collagen lysine residues) without compromising mechanics and stability in water of all resultant scaffolds. The importance of this finding is that, by reducing cross-linking, the corresponding cell-reactive carboxylate anions (collagen glutamate or aspartate residues) that are essential for integrin-mediated binding remain intact. Indeed, a 10-fold reduction in carbodiimide crosslinking resulted in near native-like cell attachment to collagen scaffolds. We have demonstrated that controlling the degree of cross-linking, and hence retaining native scaffold chemistry, offers a major step forward in the biological performance of collagen- and gelatin-based tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: This work developed collagen and gelatine-based scaffolds with structural, material and biological properties suitable for use in myocardial tissue regeneration. The novelty and significance of this research consist in elucidating the effect of the composition, origin of collagen and crosslinking concentration on the scaffold physical and cell-binding characteristics. We demonstrate that the standard carbodiimide concentrations used to crosslink collagenous scaffolds are up to 100 times higher than required for mechanical integrity in service, and stability against dissolution. The importance of this finding is that, by reducing crosslinking, the corresponding cell-reactive carboxylate anions (essential for integrin-mediated binding) remain intact and the native scaffold chemistry is retained. This offers a major step forward in the biological performance of tissue engineered scaffolds.
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.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Crosslinkers effectively improve the mechanical properties of ECM.
“Whereas they effectively improve the mechanical properties of ECM [60,192,193]”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [192]
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
Hynes (2002) · doi:10.1016/s0092-8674(02)00971-6 · Cited by 8,606 · see citing works
Stöckl, S., Göttl, C., Grifka, J. K., & Grässel, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350089 · Cited by 4,670 · see citing works
Murphy, C. M., Haugh, M. G., & O’Brien, F. J. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.063 · Cited by 2,057 · see citing works
Biomedical applications of collagen
Lee, C. H., Singla, A., & Lee, Y. (2001) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(01)00691-3 · Cited by 1,948 · see citing works
Barczyk, M., Carracedo, S., & Gullberg, D. (2010) · Cell and Tissue Research · doi:10.1007/s00441-009-0834-6 · Cited by 1,512 · see citing works
Cardiac interstitium in health and disease: The fibrillar collagen network
Weber, K. T. (1989) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(89)90360-4 · Cited by 1,060 · see citing works
Polymeric materials for bone and cartilage repair
Puppi, D., Chiellini, E., Piras, A. M., & Chiellini, E. (2010) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2010.01.006 · Cited by 913 · see citing works
Lullo, G. A. D., Sweeney, S. M., Körkkö, J., Ala‐Kokko, L., & Antonio, J. D. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110709200 · Cited by 902 · see citing works
Hollister, S. J., Maddox, R., & Taboas, J. M. (2002) · Biomaterials · doi:10.1016/s0142-9612(02)00148-5 · Cited by 715 · see citing works
Cross-linking of dermal sheep collagen using a water-soluble carbodiimide
Damink, L. H. H. O., Dijkstra, P. J., van Luyn, M. J. A., van Wachem, P. B., Nieuwenhuis, P., & Feijén, J. (1996) · Biomaterials · doi:10.1016/0142-9612(96)81413-x · Cited by 698 · see citing works
Knight, C. G., Morton, L. F., Peachey, A. R., Tuckwell, D. S., Farndale, R. W., & Barnes, M. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.35 · Cited by 695 · see citing works
Self-citationGlutaraldehyde as a crosslinking agent for collagen-based biomaterials
Damink, L. H. H. O., Dijkstra, P. J., van Luyn, M. J. A., van Wachem, P. B., Nieuwenhuis, P., & Feijén, J. (1995) · Journal of Materials Science Materials in Medicine · doi:10.1007/bf00123371 · Cited by 528 · see citing works
Park, S.-N., Park, J., Kim, H. O., Song, M. J., & Suh, H. (2002) · Biomaterials · doi:10.1016/s0142-9612(01)00235-6 · Cited by 511 · see citing works
Design and Development of Three-Dimensional Scaffolds for Tissue Engineering
Liu, C., Xia, Z., & Czernuszka, J. T. (2007) · Process Safety and Environmental Protection · doi:10.1205/cherd06196 · Cited by 483 · see citing works
Pieper, J. (1999) · Biomaterials · doi:10.1016/s0142-9612(98)00240-3 · Cited by 419 · see citing works
Methods for the treatment of collagenous tissues for bioprostheses
Khor, E. (1997) · Biomaterials · doi:10.1016/s0142-9612(96)00106-8 · Cited by 416 · see citing works
Mechanical characterization of collagen–glycosaminoglycan scaffolds
Harley, B. A. C., LEUNG, J., Silva, E. C. C. M., & Gibson, L. J. (2007) · Acta Biomaterialia · doi:10.1016/j.actbio.2006.12.009 · Cited by 397 · see citing works
Biomaterials in cardiac tissue engineering: Ten years of research survey
Chen, Q.-Z., Harding, S. E., Ali, N. N., Lyon, A. R., & Boccaccini, A. R. (2008) · Materials Science and Engineering R Reports · doi:10.1016/j.mser.2007.08.001 · Cited by 384 · see citing works
Cbfa1 Contributes to the Osteoblast-specific Expression of type I collagen Genes
Kern, B., Shen, J. J., Starbuck, M. W., & Karsenty, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006215200 · Cited by 353 · see citing works
Survival and Function of Bioengineered Cardiac Grafts
Li, R., Jia, Z., Weisel, R. D., Mickle, D. A. G., Choi, A., & Yau, T. (1999) · Circulation · doi:10.1161/01.cir.100.suppl_2.ii-63 · Cited by 350 · see citing works
Cells, scaffolds, and molecules for myocardial tissue engineering
Leor, J., Amsalem, Y., & Cohen, S. (2004) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.10.003 · Cited by 342 · see citing works
Davis, G. E. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91834-d · Cited by 338 · see citing works
Pieper, J., Hafmans, T. G. M., Veerkamp, J. H., & Kuppevelt, T. H. V. (2000) · Biomaterials · doi:10.1016/s0142-9612(99)00222-7 · Cited by 323 · see citing works
Chiu, L. L. Y., & Radisic, M. (2009) · Biomaterials · doi:10.1016/j.biomaterials.2009.09.039 · Cited by 302 · see citing works
Knight, C. G., Morton, L. F., Onley, D. J., Peachey, A. R., Messent, A., Smethurst, P. A., Tuckwell, D. S., Farndale, R. W., & Barnes, M. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.50.33287 · Cited by 284 · see citing works
Self-citationHaugh, M. G., Jaasma, M. J., & O’Brien, F. J. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31955 · Cited by 282 · see citing works
Collagen–hyaluronic acid scaffolds for adipose tissue engineering
Davidenko, N., Campbell, J. J., Thian, E. S., Watson, C. J., & Cameron, R. E. (2010) · Acta Biomaterialia · doi:10.1016/j.actbio.2010.05.005 · Cited by 259 · see citing works
Self-citationGrover, C. N., Cameron, R. E., & Best, S. M. (2012) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2012.02.028 · Cited by 250 · see citing works
Self-citationTissue and Organ Regeneration in Adults
Yannas, I. V. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1865-2 · Cited by 222 · see citing works
Evaluation of different chemical methods for cros-linking collagen gel, films and sponges
Rault, I., Frei, V., Herbage, D., Abdul‐Malak, N., & Huc, A. (1996) · Journal of Materials Science Materials in Medicine · doi:10.1007/bf00119733 · Cited by 219 · see citing works
Sashidhar, R. B., Capoor, A. K., & Ramana, D. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90081-7 · Cited by 202 · see citing works
Use of Synthetic Peptides to Locate Novel Integrin α2β1-binding Motifs in Human Collagen III
Raynal, N., Hamaia, S. W., Siljander, P. R. M., Maddox, B., Peachey, A. R., Fernandez, R. J., Foley, L. J., Slatter, D. A., Jarvis, G. E., & Farndale, R. W. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509818200 · Cited by 193 · see citing works
Self-citationOfner, C. M., & Bubnis, W. A. (1996) · Pharmaceutical Research · doi:10.1023/a:1016029023910 · Cited by 175 · see citing works
Integrin Activation State Determines Selectivity for Novel Recognition Sites in Fibrillar Collagens
Siljander, P. R. M., Hamaia, S. W., Peachey, A. R., Slatter, D. A., Smethurst, P. A., Ouwehand, W. H., Knight, C. G., & Farndale, R. W. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404685200 · Cited by 168 · see citing works
Self-citationWang, B., Borazjani, A., Tahai, M., de Jongh Curry, A. L., Simionescu, D. T., Guan, J., To, F., Elder, S. H., & Liao, J. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32781 · Cited by 164 · see citing works
Tissue and Organ Regeneration in Adults
Yannas, I. V. (2001) · Springer eBooks · doi:10.1007/b97490 · Cited by 163 · see citing works
Regulation of Type I Collagen Genes Expression
Karsenty, G., & Park, R. (1995) · International Reviews of Immunology · doi:10.3109/08830189509056711 · Cited by 160 · see citing works
Facile Modification of Collagen Directed by Collagen Mimetic Peptides
Wang, A. Y., Mo, X., Chen, C. S., & Yu, S. M. (2005) · Journal of the American Chemical Society · doi:10.1021/ja0431915 · Cited by 138 · see citing works
Regional differences in myocyte size in normal rat heart
Gerdes, A. M., Moore, J. A., Jm, H., KIRKLAND, P., & Bishop, S. P. (1986) · The Anatomical Record · doi:10.1002/ar.1092150414 · Cited by 136 · see citing works
Pugh, N., Simpson, A. M. C., Smethurst, P. A., de Groot, P. G., Raynal, N., & Farndale, R. W. (2010) · Blood · doi:10.1182/blood-2010-01-260778 · Cited by 119 · see citing works
Self-citationLee, J. E., Park, J., Hwang, Y. S., Kim, J. K., Kim, J. G., & Suh, H. (2001) · Yonsei Medical Journal · doi:10.3349/ymj.2001.42.2.172 · Cited by 101 · see citing works
Evaluation of collagen cross‐linking techniques for the stabilization of tissue matrices
Simmons, D., & Kearney, J. (1993) · Biotechnology and Applied Biochemistry · doi:10.1111/j.1470-8744.1993.tb00229.x · Cited by 91 · see citing works
Mo, X., An, Y., Yun, C., & Yu, S. M. (2006) · Angewandte Chemie International Edition · doi:10.1002/anie.200504529 · Cited by 87 · see citing works
Synergistic effects of glucose and ultraviolet irradiation on the physical properties of collagen
Ohan, M. P., Weadock, K. S., & Dunn, M. G. (2002) · Journal of Biomedical Materials Research · doi:10.1002/jbm.10111 · Cited by 87 · see citing works
Micromechanics of Fibroblast Contraction of a Collagen–GAG Matrix
Freyman, T. M., Yannas, I. V., Pek, Y.-S., Yokoo, R., & Gibson, L. J. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5302 · Cited by 85 · see citing works
Survival and Function of Bioengineered Cardiac Grafts
Li, R., Jia, Z., Weisel, R. D., Mickle, D. A. G., Choi, A., & Yau, T. M. (1999) · Circulation · doi:10.1161/circ.100.suppl_2.ii-63 · Cited by 78 · see citing works
Alteration of Cardiac Collagen Phenotypes in Hypertensive Hypertrophy: Role of Blood Pressure
Mukherjee, D., & Sen, S. (1993) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1993.1021 · Cited by 73 · see citing works
Integrin Recognition Motifs in the Human Collagens
Hamaia, S. W., & Farndale, R. W. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-9153-3_9 · Cited by 69 · see citing works
Self-citationVascular smooth muscle cell response on thin films of collagen
Elliott, J. T., Woodward, J. T., Langenbach, K. J., Tona, A., Jones, P. L., & Plant, A. L. (2005) · Matrix Biology · doi:10.1016/j.matbio.2005.07.005 · Cited by 57 · see citing works
Optimization of UV cross‐linking density for durable and nontoxic collagen GAG dermal substitute
Lew, D., Liu, P. H., & Orgill, D. P. (2006) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.30704 · Cited by 57 · see citing works
Bioactive Scaffolds for Engineering Vascularized Cardiac Tissues
Chiu, L. L. Y., Radisic, M., & Vunjak‐Novakovic, G. (2010) · Macromolecular Bioscience · doi:10.1002/mabi.201000202 · Cited by 49 · see citing works
心室筋細胞におけるgp130媒介の生存促進性/抗アポトーシス・シグナリングへのPI3K/Akt/BAD経路の関与
Kuwahara, K., Saito, Y., Kishimoto, I., Miyamoto, Y., Mm, H., Ogawa, E., Hamanaka, I., Kajiyama, N., Takahashi, N., & Izumi, T. (1999) · Circulation · Cited by 41 · see citing works
Radisic, M., & Vunjak‐Novakovic, G. (2005) · Journal of the Serbian Chemical Society · doi:10.2298/jsc0503541r · Cited by 40 · see citing works
The interplay between physical and chemical properties of protein films affects their bioactivity
Grover, C. N., Farndale, R. W., Best, S. M., & Cameron, R. E. (2012) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34187 · Cited by 24 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- [19]Barczyk M. Carracedo S. Gullberg D. Integrins Cell Tissue Res. 339 1 2010 269 280 19693543 PMC2784866
- [23]Gelatin Cole C. Encyclopaedia of Food Science and Technology 2000 John Wiley & Son 1183 1188
- [32]M.G. Haugh, The development of novel scaffolds for tissue engineering with a range of structural and mechanical properties (Ph.D. thesis), Trinity College Dublin, 2008.
- [51]Hamaia S.W. Farndale R.W. Integrin recognition motifs in collagens Adv. Exp. Med. Biol. 819 2014 127 142 25023172
Cited by
Sorted by citations
Davidenko, N., Schuster, C. F., Bax, D. V., Farndale, R. W., Hamaia, S., Best, S. M., & Cameron, R. E. (2016) · Journal of Materials Science: Materials in Medicine · doi:10.1007/s10856-016-5763-9 · Cited by 454 · see citing works
Self-citationAmani, H., Arzaghi, H., Bayandori, M., Dezfuli, A. S., Pazoki‐Toroudi, H., Shafiee, A., & Moradi, L. (2019) · Advanced Materials Interfaces · doi:10.1002/admi.201900572 · Cited by 436 · see citing works
Chemical strategies to engineer hydrogels for cell culture
Lou, J., & Mooney, D. J. (2022) · Nature Reviews Chemistry · doi:10.1038/s41570-022-00420-7 · Cited by 400 · see citing works
Biopolymers: Applications in wound healing and skin tissue engineering
Sahana, T. G., & Rekha, P. D. (2018) · Molecular Biology Reports · doi:10.1007/s11033-018-4296-3 · Cited by 371 · see citing works
Current methods of collagen cross-linking: Review
Adamiak, K., & Sionkowska, A. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.06.075 · Cited by 342 · see citing works
Joyce, K., Fabra, G. T., Bozkurt, Y., & Pandit, A. S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00512-8 · Cited by 333 · see citing works
Novel Biomedical Applications of Crosslinked Collagen
Gu, L., Shan, T., Ma, Y.-X., Tay, F. R., & Niu, L. (2019) · Trends in Biotechnology · doi:10.1016/j.tibtech.2018.10.007 · Cited by 305 · see citing works
Chouhan, D., Lohe, T., Samudrala, P. K., & Mandal, B. B. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201801092 · Cited by 234 · see citing works
Food safety considerations and research priorities for the cultured meat and seafood industry
Ong, K. J., Johnston, J., Datar, I., Sewalt, V. J. H., Holmes, D., & Shatkin, J. A. (2021) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12853 · Cited by 232 · see citing works
Collagen: a network for regenerative medicine
Pawelec, K. M., Best, S. M., & Cameron, R. E. (2016) · Journal of Materials Chemistry B · doi:10.1039/c6tb00807k · Cited by 219 · see citing works
Self-citationZhu, S., Yuan, Q., Yin, T., You, J., Gu, Z., Xiong, S., & Hu, Y. (2018) · Journal of Materials Chemistry B · doi:10.1039/c7tb02999c · Cited by 214 · see citing works
Collagen-Based Tissue Engineering Strategies for Vascular Medicine
Copes, F., Pien, N., Vlierberghe, S. V., Boccafoschi, F., & Mantovani, D. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00166 · Cited by 203 · see citing works
Recent development and biomedical applications of decellularized extracellular matrix biomaterials
Yao, Q., Zheng, Y., Lan, Q.-H., Kou, L., Xu, H., & Zhao, Y. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.109942 · Cited by 176 · see citing works
Bax, D. V., Davidenko, N., Gullberg, D., Hamaia, S. W., Farndale, R. W., Best, S. M., & Cameron, R. E. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.11.059 · Cited by 173 · see citing works
Self-citationNair, M., Johal, R. K., Hamaia, S. W., Best, S. M., & Cameron, R. E. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120109 · Cited by 165 · see citing works
Self-citationInsights on Chemical Crosslinking Strategies for Proteins
Jayachandran, B., Thansila Parvin, N., Alam, M. M., Chanda, K., & Balamurali, M. M. (2022) · Molecules · doi:10.3390/molecules27238124 · Cited by 161 · see citing works
Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges
Beldjilali‐Labro, M., Garcia, A. G., Farhat, F., Bédoui, F., Grosset, J.-F., Dufresne, M., & Legallais, C. (2018) · Materials · doi:10.3390/ma11071116 · Cited by 153 · see citing works
The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited
Dzobo, K., Senthebane, D. A., & Dandara, C. (2023) · Cancers · doi:10.3390/cancers15020376 · Cited by 146 · see citing works
Dave, K., & Gomes, V. G. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110078 · Cited by 138 · see citing works
Natural Biomaterials for Cardiac Tissue Engineering: A Highly Biocompatible Solution
Majid, Q. A., Fricker, A. T. R., Gregory, D. A., Davidenko, N., Hernández‐Cruz, O., Jabbour, R. J., Owen, T. J., Basnett, P., Lukasiewicz, B., Stevens, M. M., et al. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.554597 · Cited by 135 · see citing works
Self-citationBiomaterials for Bioprinting Microvasculature
Barrs, R. W., Jia, J., Silver, S. E., Yost, M. J., & Mei, Y. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00027 · Cited by 133 · see citing works
Emerging therapies for cartilage regeneration in currently excluded ‘red knee’ populations
Martín, A. R., Patel, J., Zlotnick, H. M., Carey, J. L., & Mauck, R. L. (2019) · npj Regenerative Medicine · doi:10.1038/s41536-019-0074-7 · Cited by 127 · see citing works
Yu, H., Zhao, H., Huang, C., & Du, Y. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.6b00620 · Cited by 121 · see citing works
Krishnakumar, G. S., Sampath, S., Muthusamy, S., & John, M. A. (2019) · Materials Science and Engineering: C · doi:10.1016/j.msec.2018.11.081 · Cited by 114 · see citing works
Ding, X., Yu, Y., Li, W., & Zhao, Y. (2023) · Matter · doi:10.1016/j.matt.2023.01.001 · Cited by 117 · see citing works
Davidenko, N., Bax, D. V., Schuster, C. F., Farndale, R. W., Hamaia, S. W., Best, S. M., & Cameron, R. E. (2015) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-015-5627-8 · Cited by 113 · see citing works
Self-citationPupkaitė, J., Rosenquist, J., Hilborn, J. G., & Samanta, A. (2019) · Biomacromolecules · doi:10.1021/acs.biomac.9b00769 · Cited by 112 · see citing works
Deng, A., Yang, Y., Du, S., Yang, X., Pang, S., Wang, X., & Yang, S. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111555 · Cited by 108 · see citing works
Diane, U., Yang, F., Long, D., Hao, Z., Dai, J. H., & Zhao, A. (2020) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01781 · Cited by 102 · see citing works
Agarwal, G., Kumar, N., & Srivastava, A. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111518 · Cited by 92 · see citing works
Nair, M., Best, S. M., & Cameron, R. E. (2020) · Applied Sciences · doi:10.3390/app10196911 · Cited by 93 · see citing works
Self-citationHe, Y., Wang, C., Wang, C., Xiao, Y., & Lin, W. J. (2021) · Polymers · doi:10.3390/polym13142299 · Cited by 87 · see citing works
Wang, P., Thissen, H. W., & Kingshott, P. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.08.054 · Cited by 83 · see citing works
Govindarajan, D., Duraipandy, N., Srivatsan, K. V., Lakra, R., Korrapati, P. S., Jayavel, R., & Kiran, M. S. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b05842 · Cited by 83 · see citing works
Andreassen, R. C., Rønning, S. B., Solberg, N. T., Grønlien, K. G., Kristoffersen, K. A., Høst, V., Kolset, S. O., & Pedersen, M. E. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121602 · Cited by 81 · see citing works
Flaig, I. A., Radenković, M. B., Najman, S. J., Pröhl, A., Jung, O., & Barbeck, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124518 · Cited by 79 · see citing works
Xu, Y. F., Dai, J., Zhu, X., Cao, R., Song, N., Liu, M., Liu, X., Zhu, J., Pan, F., Qin, L., et al. (2021) · Advanced Materials · doi:10.1002/adma.202106755 · Cited by 78 · see citing works
Dorazilová, J., Muchová, J., Šmerková, K., Kočiová, S., Diviš, P., Kopel, P., Veselý, R., Pavliňáková, V., Adam, V., & Vojtová, L. (2020) · Nanomaterials · doi:10.3390/nano10101971 · Cited by 74 · see citing works
Multiscale Porosity in Compressible Cryogenically 3D Printed Gels for Bone Tissue Engineering
Gupta, D., Singh, A. K., Dravid, A., & Bellare, J. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b05460 · Cited by 70 · see citing works
Helling, A. L., Tsekoura, E. K., Biggs, M., Bayon, Y., Pandit, A., & Zeugolis, D. I. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.5b00563 · Cited by 68 · see citing works
Redmond, J., McCarthy, H. O., Buchanan, P., Levingstone, T. J., & Dunne, N. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.111944 · Cited by 67 · see citing works
Bhattacharjee, P., & Ahearne, M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13030319 · Cited by 66 · see citing works
Xu, S., Gu, M., Wu, K., & Li, G. (2019) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.9b05006 · Cited by 66 · see citing works
Comprehensive assessment of Nile tilapia skin collagen sponges as hemostatic dressings
Sun, L., Li, B., Song, W., Zhang, K., Fan, Y., & Hou, H. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110532 · Cited by 66 · see citing works
Krishnakumar, G. S., Gostyńska, N., Dapporto, M., Campodoni, E., Montesi, M., Panseri, S., Tampieri, A., Kon, E., Marcacci, M., Sprio, S., et al. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.08.076 · Cited by 67 · see citing works
3D scaffolds in the treatment of diabetic foot ulcers: New trends vs conventional approaches
Glover, K., Stratakos, A. C., Váradi, A., & Lamprou, D. A. (2021) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2021.120423 · Cited by 65 · see citing works
Natarajan, J., Sanapalli, B. K. R., Bano, M., Singh, S. K., Gulati, M., & Karri, V. V. S. R. (2019) · Advances in Wound Care · doi:10.1089/wound.2018.0831 · Cited by 65 · see citing works
Pien, N., Pezzoli, D., Hoorick, J. V., Copes, F., Vansteenland, M., Albu, M., Meulenaer, B. D., Mantovani, D., Vlierberghe, S. V., & Dubruel, P. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112460 · Cited by 66 · see citing works
Bax, D. V., Davidenko, N., Hamaia, S. W., Farndale, R. W., Best, S. M., & Cameron, R. E. (2019) · Acta Biomaterialia · doi:10.1016/j.actbio.2019.09.046 · Cited by 62 · see citing works
Self-citationLi, Y.-C. E., Jodat, Y. A., Samanipour, R., Zorzi, G., Zhu, K., Hirano, M., Chang, K., Arnaout, A., Hassan, S., Matharu, N., et al. (2021) · Biofabrication · doi:10.1088/1758-5090/abc1be · Cited by 61 · see citing works
Krishnakumar, G. S., Gostyńska, N., Campodoni, E., Dapporto, M., Montesi, M., Panseri, S., Tampieri, A., Kon, E., Marcacci, M., Sprio, S., et al. (2017) · Materials Science and Engineering C · doi:10.1016/j.msec.2017.03.255 · Cited by 60 · see citing works
Engineering a collagen matrix for cell‐instructive regenerative angiogenesis
Minor, A. J., & Coulombe, K. L. K. (2020) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.34573 · Cited by 57 · see citing works
Ahmed, Z., Powell, L. C., Matin, N., Mearns‐Spragg, A., Thornton, C. A., Khan, I. M., & Francis, L. W. (2021) · Marine Drugs · doi:10.3390/md19080405 · Cited by 56 · see citing works
Sun, L., Li, B., Yao, D., Song, W., & Hou, H. (2018) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2018.01.006 · Cited by 56 · see citing works
Sun, T., Zhu, Y., & Chen, F. (2018) · RSC Advances · doi:10.1039/c8ra03972k · Cited by 56 · see citing works
Malcor, J.-D. M., Bax, D. V., Hamaia, S. W., Davidenko, N., Best, S. M., Cameron, R. E., Farndale, R. W., & Bihan, D. G. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.01.044 · Cited by 55 · see citing works
Self-citationTypes of Crosslinkers and Their Applications in Biomaterials and Biomembranes
Yammine, P., Safadi, A. E., Kassab, R., El‐Nakat, H., Obeid, P. J., Nasr, Z., Tannous, T., Sari‐Chmayssem, N., Mansour, A., & Chmayssem, A. (2025) · Chemistry · doi:10.3390/chemistry7020061 · Cited by 54 · see citing works
Sun, T., Yu, W., Zhu, Y., Chen, F., Zhang, Y., Jiang, Y., & He, Y. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201800425 · Cited by 54 · see citing works
Cross-linked silk sericin–gelatin 2D and 3D matrices for prospective tissue engineering applications
Kumar, J. P., Bhardwaj, N., & Mandal, B. B. (2016) · RSC Advances · doi:10.1039/c6ra18654h · Cited by 53 · see citing works
Elastic Anisotropy Governs the Range of Cell-Induced Displacements
Goren, S., Koren, Y., Xu, X., & Lesman, A. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2019.12.033 · Cited by 54 · see citing works
Rueda-Gensini, L., Serna, J. A., Cifuentes, J., Cruz, J. C., & Muñoz-Camargo, C. (2021) · International Journal of Bioprinting · doi:10.18063/ijb.v7i3.353 · Cited by 52 · see citing works
An arterial constitutive model accounting for collagen content and cross-linking
Holzapfel, G. A., & Ogden, R. W. (2019) · Journal of the Mechanics and Physics of Solids · doi:10.1016/j.jmps.2019.103682 · Cited by 51 · see citing works
Properties and characterization of bone repair materials
Pawelec, K. M., White, A. A., & Best, S. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-08-102451-5.00004-4 · Cited by 51 · see citing works
Self-citationThomas, J., Sharma, A., Panwar, V., Chopra, V., & Ghosh, D. (2019) · ACS Applied Bio Materials · doi:10.1021/acsabm.9b00074 · Cited by 50 · see citing works
Akhshabi, S., Biazar, E., Singh, V., Keshel, S. H., & Geetha, N. M. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s165739 · Cited by 48 · see citing works
Ellermann, E., Meyer, N., Cameron, R. E., & Best, S. M. (2023) · Regenerative Biomaterials · doi:10.1093/rb/rbad027 · Cited by 47 · see citing works
Self-citationShepherd, J. H., Howard, D. J., Waller, A. K., Foster, H. R., Mueller, A., Moreau, T., Evans, A., Arumugam, M. Q., Bouet, G., Vriend, E., et al. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.08.019 · Cited by 47 · see citing works
Self-citationSánchez‐Cid, P., Alonso‐González, M., Jiménez‐Rosado, M., Benhnia, M. R., Ruíz-Mateos, E., Ostos, F. J., Romero, A., & Puyana, V. M. P. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.129858 · Cited by 46 · see citing works
Davidenko, N., Hamaia, S. W., Bax, D. V., Malcor, J.-D. M., Schuster, C. F., Gullberg, D., Farndale, R. W., Best, S. M., & Cameron, R. E. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.10.035 · Cited by 45 · see citing works
Self-citationWalimbe, T., & Panitch, A. (2020) · Bioengineering · doi:10.3390/bioengineering7040156 · Cited by 45 · see citing works
3D-Printed Hybrid Collagen/GelMA Hydrogels for Tissue Engineering Applications
Nagaraj, A., Etxabide, A., Naffa, R., Zidan, G., & Seyfoddin, A. (2022) · Biology · doi:10.3390/biology11111561 · Cited by 44 · see citing works
Zhou, S., Chang, Q., Lu, F., & Xing, M. M. Q. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700131 · Cited by 44 · see citing works
Bak, S. Y., Lee, S. W., Choi, C., & Kim, H. W. (2018) · Materials · doi:10.3390/ma11122518 · Cited by 44 · see citing works
Scaffold Biomaterials in the Development of Cultured Meat: A Review
Park, S., Ryoo, J.-H., Kwon, H.-C., & Han, S. G. (2025) · Food Science of Animal Resources · doi:10.5851/kosfa.2025.e13 · Cited by 43 · see citing works
Suzuki, A., Kodama, Y., Miwa, K., Kishimoto, K., Hoshikawa, E., Haga, K., Sato, T., Mizuno, J., & Izumi, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-79114-3 · Cited by 43 · see citing works
Modeling the Mechanobiology of Cancer Cell Migration Using 3D Biomimetic Hydrogels
Morales, X., Cortés‐Domínguez, I., & Ortíz-de-Solórzano, C. (2021) · Gels · doi:10.3390/gels7010017 · Cited by 44 · see citing works
Choi, H. J., Kim, Y., Suh, J., & Han, J. Y. (2021) · Materials Science and Engineering C · doi:10.1016/j.msec.2021.112350 · Cited by 42 · see citing works
A novel personalized 3D injectable protein scaffold for regenerative medicine
Anitua, E., Pino, A., Troya, M., Jaén, P., & Orive, G. (2017) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-017-6012-6 · Cited by 42 · see citing works
An Overview of Collagen-Based Composite Scaffold for Bone Tissue Engineering
Vijayalekha, A., Anandasadagopan, S. K., & Pandurangan, A. K. (2023) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-023-04318-y · Cited by 41 · see citing works
Suzuki, A., Kato, H., Kawakami, T., Kodama, Y., Shiozawa, M., Kuwae, H., Miwa, K., Hoshikawa, E., Haga, K., Shiomi, A., et al. (2020) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2019.1706147 · Cited by 41 · see citing works
Hyaluronic acid microneedles‐laden collagen cryogel plugs for ocular drug delivery
Saraswathy, K., Agarwal, G., & Srivastava, A. (2020) · Journal of Applied Polymer Science · doi:10.1002/app.49285 · Cited by 41 · see citing works
Manohar, D., Babu, R. S., Vijaya, B., Nallakumar, S., Gobi, R., Anand, S., Nishanth, D. S., Anupama, A., & Rani, M. U. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.137318 · Cited by 39 · see citing works
Dry versus hydrated collagen scaffolds: are dry states representative of hydrated states?
Suchý, T., Šupová, M., Bartoš, M., Sedláček, R., Piola, M., Soncini, M., Fiore, G. B., Sauerová, P., & Kalbáčová, M. H. (2018) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-017-6024-2 · Cited by 39 · see citing works
Bortolomai, I., Sandri, M., Draghici, E., Fontana, E., Campodoni, E., Marcovecchio, G. E., Ferrua, F., Perani, L., Spinelli, A. E., Canu, T., et al. (2019) · Stem Cells Translational Medicine · doi:10.1002/sctm.18-0218 · Cited by 39 · see citing works
Grønlien, K. G., Pedersen, M. E., Sanden, K. W., Høst, V., Karlsen, J. R., & Tønnesen, H. H. (2019) · Sustainable Chemistry and Pharmacy · doi:10.1016/j.scp.2019.100166 · Cited by 39 · see citing works
Materials science perspective of multifunctional materials derived from collagen
Ashokkumar, M., & Ajayan, P. M. (2020) · International Materials Reviews · doi:10.1080/09506608.2020.1750807 · Cited by 38 · see citing works
Chachques, J. C., Gardin, C., Lila, N., Ferroni, L., Migonney, V., Falentin‐Daudre, C., Zanotti, F., Trentini, M., Brunello, G., Rocca, T., et al. (2021) · Biomedicines · doi:10.3390/biomedicines9070824 · Cited by 37 · see citing works
Cao, R., Yang, X., Xu, Y. F., Brand, D. D., Zhou, G., Xiao, K., Xia, H., & Czernuszka, J. T. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202101643 · Cited by 36 · see citing works
Biocompatible Fe3O4/chitosan scaffolds with high magnetism
Ge, J., Zhai, M., Zhang, Y., Bian, J., & Wu, J. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.01.077 · Cited by 48 · see citing works
Decellularized tilapia fish skin: A novel candidate for tendon tissue engineering
Liu, Z., Yu, M.-Z., Peng, H., Liu, R.-T., Lim, T., Zhang, C.-Q., Zhu, Z.-Z., & Wei, X.-J. (2022) · Materials Today Bio · doi:10.1016/j.mtbio.2022.100488 · Cited by 35 · see citing works
3D porous collagen scaffolds reinforced by glycation with ribose for tissue engineering application
Gostyńska, N., Krishnakumar, G. S., Campodoni, E., Panseri, S., Montesi, M., Sprio, S., Kon, E., Marcacci, M., Tampieri, A., & Sandri, M. (2017) · Biomedical Materials · doi:10.1088/1748-605x/aa7694 · Cited by 33 · see citing works
Extrusion-based 3D bioprinting of alginate-based tissue constructs
Shah, P. P., Shah, H. B., Maniar, K. K., & Özel, T. (2020) · Procedia CIRP · doi:10.1016/j.procir.2020.06.007 · Cited by 33 · see citing works
Mechanical and Degradation Properties of Hybrid Scaffolds for Tissue Engineered Heart Valve (TEHV)
Nazir, R., Bruyneel, A. A. N., Carr, C. A., & Czernuszka, J. T. (2021) · Journal of Functional Biomaterials · doi:10.3390/jfb12010020 · Cited by 33 · see citing works
UV-mediated solid-state cross-linking of electrospinning nanofibers of modified collagen
Song, X., Dong, P., Gravesande, J., Cheng, B., & Xing, J. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2018.09.029 · Cited by 33 · see citing works
Xie, X., Li, X., Lei, J., Zhao, X., Lyu, Y., Mu, C., Li, D., Ge, L., & Xu, Y. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111165 · Cited by 32 · see citing works
Bidirectional Mechanical Response Between Cells and Their Microenvironment
Mierke, C. T. (2021) · Frontiers in Physics · doi:10.3389/fphy.2021.749830 · Cited by 33 · see citing works
Natural origin bilayer pullulan-PHBV scaffold for wound healing applications
Dalgıç, A. D., Koman, E., Karataş, A. Y., Tezcaner, A., & Keskin, D. S. (2021) · Biomaterials Advances · doi:10.1016/j.msec.2021.112554 · Cited by 32 · see citing works
Sani, M., Hosseinie, R., Latifi, M., Shadi, M., Razmkhah, M., Salmannejad, M., Parsaei, H., & Talaei‐Khozani, T. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.213019 · Cited by 33 · see citing works
Pawelec, K. M., Confalonieri, D., Ehlicke, F., van Boxtel, H. A., Walles, H., & Kluijtmans, S. G. J. M. (2017) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.36049 · Cited by 32 · see citing works
Three-dimensional bioprinting is not only about cell-laden structures
Zhang, H., Xing, T., Yin, R.-X., Shi, Y., Yang, S.-M., & Zhang, W.-J. (2016) · Chinese Journal of Traumatology · doi:10.1016/j.cjtee.2016.06.007 · Cited by 31 · see citing works
- Authors
- Davidenko, N., Schuster, C. F., Bax, D. V., Raynal, N., Farndale, R. W., Best, S. M., & Cameron, R. E.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Davidenko, N.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 25
- Pages
- 131-142
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC4570933
- OpenAlex
- W973162690
- Cited by
- 276
- References
- 54
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 19 · 2023: 18 · 2022: 26 · 2021: 40 · 2020: 41 · 2019: 36 · 2018: 21 · 2017: 17 · 2016: 14 · 2015: 1
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Biomaterialia (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- British Heart Foundation (NH/11/1/28922, RG/09/003/27122)
- ERC Advanced (320598 3D-E)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- collagen scaffolds, gelatin, crosslinking, carbodiimides, crosslink density, scaffold stability, degradation, mechanical properties, integrin binding, cell attachment, porous scaffolds, swelling, carboxylate, tissue engineering biomaterials, porosity control, freeze-drying
- MeSH terms
- Amines, Animals, Carbodiimides, Cattle, Cell Communication, Collagen, Cross-Linking Reagents, Humans, Microscopy, Electron, Scanning, Peptides, Rheology, Solubility, Suspensions, Viscosity, Water, Porosity, Microscopy, Confocal, Cell Line, Tumor, Tissue Scaffolds, Mechanical Phenomena
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
