Degradable Poly(2-hydroxyethyl methacrylate)-co-polycaprolactone Hydrogels for Tissue Engineering Scaffolds
Open accessAbstract
Biodegradable poly(2-hydroxyethyl methacrylate)(pHEMA) hydrogels for engineered tissue constructs were developed by the use of atom transfer radical polymerization (ATRP), a degradable cross-linker, and a macroinitiator. Hydrogels are appropriate materials for tissue engineering scaffolds because of their tissue-like mechanical compliance and mass transfer properties. However, many hydrogels that have seen wide application in medicine are not biodegradable or cannot be easily cleared from the body. pHEMA was selected for the scaffold material because of its reasonable mechanical strength, elasticity, and long history of successful use in medicine as well as because it can be easily fabricated into numerous configurations. pHEMA was studied at various molecular weights between 2 and 50 kDa. The molecular weight range suitable for renal clearance was an important factor in the experimental design. The fabricated hydrogels contain oligomeric blocks of polycaprolactone (PCL), a hydrolytically and enzymatically degradable polymer, as a cross-linking agent. In addition, a degradable macroinitiator that also contained oligomeric PCL was used to initiate the ATRP. The chain length, cross-link density, and polymerization solvent were found to affect the mechanical properties of the pHEMA hydrogels. Degradation of the pHEMA hydrogels was characterized by the use of 0.007 M NaOH, lipase solutions, and phosphate-buffered saline. The mass loss, swelling ratio, and tensile modulus were evaluated. Degradation products after sodium hydroxide treatment were measured by the use of gel permeation chromatography (GPC) to verify the polymer lengths and polydispersity. Erosion was observed in only the sodium hydroxide and lipase solutions. However, the swelling ratio and tensile modulus indicate bulk degradation in all PCL-containing samples. Degradable hydrogels in enzymatic solutions showed 30% mass loss in 16 weeks. Initial cell toxicity studies indicate no adverse cellular response to the hydrogels or their degradation products. These hydrogels have appropriate mechanical properties and a tunable degradation rate, and they are composed of materials that are currently in FDA-approved devices. Therefore, the degradable pHEMA developed in this study has considerable potential as a scaffold for tissue engineering applications, in cardiac and other applications.
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Myocardial scar tissue elastic modulus is 4,700 ± 1,400 kPa.
“Here, the elastic modulus of the solid polymer (155 ± 14 kPa) is similar to that of rat myocardium (590 ± 22 kPa) (14), whereas porous constructs (12 ± 6 kPa) are one order of magnitude lower than myocardial tissue and two orders of magnitude below myocardial scar tissue (4,700 ± 1,400 kPa) (14).”
From Proangiogenic scaffolds as functional templates for cardiac tissue engineering (2010) · cites this paper as [14]
Rat myocardium elastic modulus is 590 ± 22 kPa.
“Here, the elastic modulus of the solid polymer (155 ± 14 kPa) is similar to that of rat myocardium (590 ± 22 kPa) (14), whereas porous constructs (12 ± 6 kPa) are one order of magnitude lower than myocardial tissue and two orders of magnitude below myocardial scar tissue (4,700 ± 1,400 kPa) (14).”
From Proangiogenic scaffolds as functional templates for cardiac tissue engineering (2010) · cites this paper as [14]
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Cites
Atom Transfer Radical Polymerization
Matyjaszewski, K. A., & Xia, J. (2001) · Chemical Reviews · doi:10.1021/cr940534g · Cited by 7,646 · see citing works
Biodegradable polymers as biomaterials
Nair, L. S., & Laurencin, C. T. (2007) · Progress in Polymer Science · doi:10.1016/j.progpolymsci.2007.05.017 · Cited by 4,416 · see citing works
Sawhney, A. S., Pathak, C. P., & Hubbell, J. A. (1993) · Macromolecules · doi:10.1021/ma00056a005 · Cited by 969 · see citing works
Bryant, S. J., & Anseth, K. S. (2002) · Journal of Biomedical Materials Research · doi:10.1002/jbm.1217 · Cited by 845 · see citing works
Self-citationA novel degradable polycaprolactone networks for tissue engineering
Kweon, H. (2002) · Biomaterials · doi:10.1016/s0142-9612(02)00370-8 · Cited by 686 · see citing works
Bioengineered Cardiac Grafts : A New Approach to Repair the Infarcted Myocardium?
Leor, J., Etzion, S., Dar, A., Shapiro, L., Barbash, I. M., Battler, A., Granot, Y., & Cohen, S. (2000) · Circulation · doi:10.1161/01.cir.102.suppl_3.iii-56 · Cited by 559 · see citing works
Tissue engineering of vascularized cardiac muscle from human embryonic stem cells
Caspi, O., Lesman, A., Basevitch, Y., Gepstein, A., Arbel, G., Habib, I. H. M., Gepstein, L., & Levenberg, S. (2007) · Circulation Research · doi:10.1161/01.res.0000257776.05673.ff · Cited by 558 · see citing works
The intracellular degradation of poly(ε‐caprolactone)
Woodward, S. C., Brewer, P. S., Moatamed, F., Schindler, A., & Pitt, C. G. (1985) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820190408 · Cited by 380 · see citing works
Pharmacokinetics and Biodistribution of Novel Aptamer Compositions
Healy, J. M., Lewis, S. D., Kurz, M., Boomer, R. M., Thompson, K. M., Wilson, C., & McCauley, T. G. (2004) · Pharmaceutical Research · doi:10.1007/s11095-004-7676-4 · Cited by 300 · see citing works
Atom Transfer Radical Polymerization of 2-Hydroxyethyl Methacrylate
Beers, K. L., Boo, S., Gaynor, S. G., et al. (1999) · Macromolecules · doi:10.1021/ma990176p · Cited by 288 · see citing works
Stimulus-Responsive Water-Soluble Polymers Based on 2-Hydroxyethyl Methacrylate
Weaver, J. V. M., Bannister, I., Robinson, K. L., Bories-Azeau, X., Armes, S. P., Smallridge, M. J., & McKenna, P. (2004) · Macromolecules · doi:10.1021/ma0356358 · Cited by 273 · see citing works
Thomas Eschenhagen, A., & Zimmermann, W. H. (2005) · Circulation Research · doi:10.1161/01.res.0000196562.73231.7d · Cited by 261 · see citing works
Bio‐Compatibility in selection of materials for implantation
Homsy, C. A. (1970) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820040306 · Cited by 239 · see citing works
The structure of highly crosslinked poly(2‐hydroxyethyl methacrylate) hydrogels
Peppas, N. A., Moynihan, H. J., & Lucht, L. M. (1985) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820190405 · Cited by 231 · see citing works
Human embryonic stem cell transplantation to repair the infarcted myocardium
Leor, J., Gerecht, S., Cohen, S., Miller, L., Holbová, R., Ziskind, A., Shachar, M., Feinberg, M. S., Guetta, E., & Itskovitz‐Eldor, J. (2007) · Heart · doi:10.1136/hrt.2006.093161 · Cited by 206 · see citing works
Degradable-Brushed pHEMA–pDMAEMA Synthesized via ATRP and Click Chemistry for Gene Delivery
Jiang, X., Lok, M. C., & Hennink, W. E. (2007) · Bioconjugate Chemistry · doi:10.1021/bc0701186 · Cited by 190 · see citing works
Bakshi, A., Fisher, O. Z., Dağcı, T., et al. (2004) · Journal of Neurosurgery Spine · doi:10.3171/spi.2004.1.3.0322 · Cited by 160 · see citing works
Clinical evaluation of the Capronor contraceptive implant: Preliminary report
Darney, P. D., Monroe, S. E., Klaisle, C., et al. (1989) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(89)80015-8 · Cited by 126 · see citing works
Nanofabrication and Microfabrication of Functional Materials for Tissue Engineering
Park, H., Cannizzaro, C., Vunjak‐Novakovic, G., Langer, R., Vacanti, C. A., & Farokhzad, O. C. (2007) · Tissue Engineering · doi:10.1089/ten.2006.0198 · Cited by 123 · see citing works
Metters, A. T., Anseth, K. S., & Bowman, C. N. (2001) · The Journal of Physical Chemistry B · doi:10.1021/jp004083h · Cited by 113 · see citing works
Rice, M. A., Sanchez‐Adams, J., & Anseth, K. S. (2006) · Biomacromolecules · doi:10.1021/bm060086+ · Cited by 110 · see citing works
Cell adhesion and mechanical properties of a flexible scaffold for cardiac tissue engineering
Hidalgo‐Bastida, A., Barry, J. J. A., Everitt, N. M., et al. (2007) · Acta Biomaterialia · doi:10.1016/j.actbio.2006.12.006 · Cited by 105 · see citing works
Rice, M. A., & Anseth, K. S. (2004) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30106 · Cited by 97 · see citing works
Transport through crosslinked poly(2‐hydroxyethyl methacrylate) hydrogel membranes
Ratner, B. D., & Miller, I. F. (1973) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820070407 · Cited by 95 · see citing works
Self-citationLeor, J., Etzion, S., Dar, A., Shapiro, L., Barbash, I. M., Battler, A., Granot, Y., & Cohen, S. (2000) · Circulation · doi:10.1161/circ.102.suppl_3.iii-56 · Cited by 89 · see citing works
Huan, K., Bes, L., Haddleton, D. M., & Khoshdel, E. (2001) · Journal of Polymer Science Part A Polymer Chemistry · doi:10.1002/pola.1161 · Cited by 77 · see citing works
Processing of polycaprolactone porous structure for scaffold development
Tay, B. Y., Zhang, S., Myint, M. H., et al. (2006) · Journal of Materials Processing Technology · doi:10.1016/j.jmatprotec.2006.07.016 · Cited by 74 · see citing works
Báez, J. E., Marcos-Fernández, Á. A., Lebrón‐Aguilar, R., & Martínez‐Richa, A. (2006) · Polymer · doi:10.1016/j.polymer.2006.10.023 · Cited by 39 · see citing works
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Research works printed but not linked: 3
- [5]Hidalgo-Bastida LA Barry JJ Everitt NM Rose FR Buttery LD Hall IP Claycomb WC Shaksheff KM Acta Biomater 2007 3 457 62 17321810
- [19]Tay BY Zhang SX Myint MH Ng FL Chandrasekaran M Tan LKA Journal of Materials Processing Technology 2007 182 117 121
- [26]Huan K Bes L Haddleton DM Khoshdel E Journal of Polymer Science 2001 39 1833 1842
Cited by
Sorted by citations
Designing degradable hydrogels for orthogonal control of cell microenvironments
Kharkar, P. M., Kiick, K. L., & Kloxin, A. M. (2013) · Chem. Soc. Rev. · doi:10.1039/c3cs60040h · Cited by 717 · see citing works
Proangiogenic scaffolds as functional templates for cardiac tissue engineering
Madden, L. R., Mortisen, D. J., Sussman, E. M., Dupras, S. K., Fugate, J. A., Cuy, J. L., Hauch, K. D., Laflamme, M. A., Murry, C. E., & Ratner, B. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006442107 · Cited by 662 · see citing works
Self-citationTardy, A., Nicolas, J., Gigmes, D., Lefay, C., & Guillaneuf, Y. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00319 · Cited by 469 · see citing works
Chandel, A. K. S., Kumar, C. U., & Jewrajka, S. K. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b10675 · Cited by 98 · see citing works
Zhang, Y., Chu, D., Zheng, M., Kissel, T., & Agarwal, S. (2012) · Polymer Chemistry · doi:10.1039/c2py20403g · Cited by 86 · see citing works
- Authors
- Atzet, S., Curtin, S., Trinh, P., Bryant, S., & Ratner, B.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Ratner, Buddy
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-12-08
- Volume
- 9
- Issue
- 12
- Pages
- 3370-3377
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- PMC
- PMC2650022
- OpenAlex
- W1976503000
- Cited by
- 173
- References
- 28
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 10 · 2023: 11 · 2022: 8 · 2021: 9 · 2020: 13 · 2019: 3 · 2018: 8 · 2017: 15 · 2016: 6 · 2015: 16 · 2014: 9 · 2013: 16 · 2012: 14
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomacromolecules (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01hl064387-10)
- National Heart, Lung, and Blood Institute (R01-HL064387, HL-64387, R24HL064387)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- poly(2-hydroxyethyl methacrylate), polycaprolactone, hydrogels, tissue engineering scaffolds, biodegradable polymers, atom transfer radical polymerization, macroinitiator, enzymatic degradation, lipase, hydrolytic degradation, renal clearance, molecular weight, crosslink density, swelling ratio, tensile modulus, cytotoxicity, cardiac tissue engineering
- MeSH terms
- Animals, Biocompatible Materials, Cross-Linking Reagents, Elasticity, Fibroblasts, Polyesters, Polymethacrylic Acids, Molecular Structure, 3T3 Cells, Hydrogels, Tissue Engineering, Mice, Tissue Scaffolds
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