Skip to main content Accessibility help
×
Home
  • Print publication year: 2014
  • Online publication date: February 2015

16 - Fumarate-based hydrogels in regenerative medicine applications

from Part III - Hydrogel scaffolds for regenerative medicine

Summary

Introduction

Hydrogels are an excellent scaffold structure for numerous applications in tissue engineering and regenerative medicine. In particular, they can be used as cell and drug carriers to deliver such therapeutic components directly and locally [1]. Hydrogels can be injected and crosslinked in situ, reducing the need for risky invasive surgeries [2]. In addition, hydrogels can mimic the natural extracellular matrix (ECM) environment, and allow one to control cellular and tissue functions as well as the transport of nutrients and bioactive molecules [3, 4].

Fumarate-based hydrogels are synthetic polymers, allowing flexible control of physical, mechanical, and degradative properties for a desired application [4]. Fumaric acid, the fundamental component of these hydrogel scaffolds, is an unsaturated organic acid that is commonly found in the human body and can be metabolized through the Krebs cycle [5–7]. Polymer chains that contain fumarate units crosslink easily via the unsaturated double bonds and degrade through hydrolysis of the ester bonds in the fumarate group [6–9]. Furthermore, the biodegradable nature of these hydrogels allows neotissue ingrowth and eliminates the need for further surgery to remove the implanted scaffold [5, 10].

References
Temenoff, J. S., Park, H., Jabbari, E. et al. 2004. In vitro osteogenic differentiation of marrow stromal cells encapsulated in biodegradable hydrogels. J. Biomed. Mater. Res. A, 70, 235–44.
Holland, T. A., Tessmar, J. K., Tabata, Y. and Mikos, A. G. 2004. Transforming growth factor-beta 1 release from oligo(poly(ethylene glycol) fumarate) hydrogels in conditions that model the cartilage wound healing environment. J. Control. Release, 94, 101–14.
Lee, K. Y. and Mooney, D. J. 2001. Hydrogels for tissue engineering. Chem. Rev., 101, 1869–79.
Drury, J. L. and Mooney, D. J. 2003. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. 24, 4337–51.
Temenoff, J. S., Kasper, F. K. and Mikos, A. G. 2007. Fumarate-based macromers as scaffolds for tissue engineering applications. In Topics in Tissue Engineering, ed. Ashammakhi, N., Reis, R. L. and Chiellini, E.Oulu: Expertissue E-Book, pp. 6.1–6.16.
Jo, S., Shin, H., Shung, A. K., Fisher, J. P. and Mikos, A. G. 2001. Synthesis and characterization of oligo(poly(ethylene glycol) fumarate) macromer. Macromolecules, 34, 2839–44.
Sarvestani, A. S., He, X. and Jabbari, E. 2007. Viscoelastic characterization and modeling of gelation kinetics of injectable in situ cross-linkable poly(lactide-co-ethylene oxide-co-fumarate) hydrogels. Biomacromolecules, 8, 406–15.
Behravesh, E., Shung, A. K., Jo, S. and Mikos, A. G. 2002. Synthesis and characterization of triblock copolymers of methoxy poly(ethylene glycol) and poly(propylene fumarate). Biomacromolecules, 3, 153–8.
Temenoff, J. S., Athanasiou, K. A., LeBaron, R. G. and Mikos, A. G. 2002. Effect of poly(ethylene glycol) molecular weight on tensile and swelling properties of oligo(poly(ethylene glycol) fumarate) hydrogels for cartilage tissue engineering. J. Biomed. Mater. Res., 59, 429–37.
Temenoff, J. S. and Mikos, A. G. 2000. Injectable biodegradable materials for orthopedic tissue engineering. Biomaterials, 21, 2405–12.
Suggs, L. J., Krishnan, R. S., Garcia, C. A. et al. 1998. In vitro and in vivo degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels. J. Biomed. Mater. Res., 42, 312–20.
Shin, H., Ruhe, P. Quinten, Mikos, A. G. and Jansen, J. A. 2003. In vivo bone and soft tissue response to injectable, biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels. Biomaterials, 24, 3201–11.
Shin, H., Temenoff, J. S. and Mikos, A. G. 2003. In vitro cytotoxicity of unsaturated oligo[poly(ethylene glycol) fumarate] macromers and their cross-linked hydrogels. Biomacromolecules, 4, 552–60.
He, X. and Jabbari, E. 2007. Material properties and cytocompatibility of injectable MMP degradable poly(lactide ethylene oxide fumarate) hydrogel as a carrier for marrow stromal cells. Biomacromolecules. 8, 780–92.
Behravesh, E., Zygourakis, K. and Mikos, A. G. 2003. Adhesion and migration of marrow-derived osteoblasts on injectable in situ crosslinkable poly(propylene fumarate-co-ethylene glycol)-based hydrogels with a covalently linked RGDS peptide. J. Biomed. Mater. Res. A, 65, 260–70.
Suggs, L. J., Kao, E. Y., Palombo, L. L. et al. 1998. Preparation and characterization of poly(propylene fumarate-co-ethylene glycol) hydrogels. J. Biomater. Sci. Polymer Edition, 9, 653–66.
Tanahashi, K. and Mikos, A. G. 2002. Cell adhesion on poly(propylene fumarate-co-ethylene glycol) hydrogels. J. Biomed. Mater. Res., 62, 558–66.
Fisher, J. P., Holland, T. A., Dean, D., Engel, P. S. and Mikos, A. G. 2001. Synthesis and properties of photocross-linked poly(propylene fumarate) scaffolds. J. Biomater. Sci. Polymer Edition, 12, 673–87.
Fisher, J. P., Vehof, J. W., Dean, D. et al. 2002. Soft and hard tissue response to photocrosslinked poly(propylene fumarate) scaffolds in a rabbit model, J. Biomed. Mater. Res., 59, 547–56.
Timmer, M. D., Carter, C., Ambrose, C. G. and Mikos, A. G. 2003. Fabrication of poly(propylene fumarate)-based orthopaedic implants by photo-crosslinking through transparent silicone molds. Biomaterials, 24, 4707–14.
Kim, K., Dean, D., Lu, A., Mikos, A. G. and Fisher, J. P. 2011. Early osteogenic signal expression of rat bone marrow stromal cells is influenced by both hydroxyapatite nanoparticle content and initial cell seeding density in biodegradable nanocomposite scaffolds. Acta Biomater., 7, 1249–64.
Kasper, F. K., Tanahashi, K., Fisher, J. P. and Mikos, A. G. 2009. Synthesis of poly(propylene fumarate). Nature Protoc., 4, 518–25.
Suggs, L. J., Payne, R. G., Yaszemski, M. J., Alemany, L. B. and Mikos, A. G. 1997. Synthesis and characterization of a block copolymer consisting of poly(propylene fumarate) and poly(ethylene glycol). Macromolecules, 30, 4318–23.
Shung, A. K., Behravesh, E., Jo, S. and Mikos, A. G. 2003. Crosslinking characteristics of and cell adhesion to an injectable poly(propylene fumarate-co-ethylene glycol) hydrogel using a water-soluble crosslinking system. Tissue Eng., 9, 243–54.
Behravesh, E., Jo, S., Zygourakis, K. and Mikos, A. G. 2002. Synthesis of in situ cross-linkable macroporous biodegradable poly(propylene fumarate-co-ethylene glycol) hydrogels. Biomacromolecules, 3, 374–81.
Behravesh, E., Timmer, M. D., Lemoine, J. J., Liebschner, M. A. and Mikos, A. G. 2002. Evaluation of the in vitro degradation of macroporous hydrogels using gravimetry, confined compression testing, and microcomputed tomography. Biomacromolecules, 3, 1263–70.
Suggs, L. J., Shive, M. S., Garcia, C. A., Anderson, J. M. and Mikos, A. G. 1999. In vitro cytotoxicity and in vivo biocompatibility of poly(propylene fumarate-co-ethylene glycol) hydrogels. J. Biomed. Mater. Res., 46, 22–32.
Behravesh, E. and Mikos, A. G. 2003. Three-dimensional culture of differentiating marrow stromal osteoblasts in biomimetic poly(propylene fumarate-co-ethylene glycol)-based macroporous hydrogels. J. Biomed. Mater. Res. A, 66, 698–706.
Tanahashi, K., Jo, S. and Mikos, A. G. 2002. Synthesis and characterization of biodegradable cationic poly(propylene fumarate-co-ethylene glycol) copolymer hydrogels modified with agmatine for enhanced cell adhesion. Biomacromolecules, 3, 1030–7.
Tanahashi, K. and Mikos, A. G. 2003. Effect of hydrophilicity and agmatine modification on degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels. J. Biomed. Mater. Res. A, 67, 1148–54.
Fisher, J. P., Jo, S., Mikos, A. G. and Reddi, A. H. 2004. Thermoreversible hydrogel scaffolds for articular cartilage engineering. J. Biomed. Mater. Res. A, 71, 268–74.
Dadsetan, M., Szatkowski, J. P., Yaszemski, M. J. and Lu, L. 2007. Characterization of photo-cross-linked oligo[poly(ethylene glycol) fumarate] hydrogels for cartilage tissue engineering. Biomacromolecules, 8, 1702–9.
Temenoff, J. S., Park, H., Jabbari, E. et al. 2004. Thermally cross-linked oligo(poly(ethylene glycol) fumarate) hydrogels support osteogenic differentiation of encapsulated marrow stromal cells in vitro. Biomacromolecules, 5, 5–10.
Holland, T. A., Tabata, Y. and Mikos, A. G. 2003. In vitro release of transforming growth factor-beta 1 from gelatin microparticles encapsulated in biodegradable, injectable oligo(poly(ethylene glycol) fumarate) hydrogels. J. Control. Release, 91, 299–313.
Park, H., Guo, X., Temenoff, J. S. et al. 2009. Effect of swelling ratio of injectable hydrogel composites on chondrogenic differentiation of encapsulated rabbit marrow mesenchymal stem cells in vitro. Biomacromolecules, 10, 541–6.
Temenoff, J. S., Steinbis, E. S. and Mikos, A. G. 2003. Effect of drying history on swelling properties and cell attachment to oligo(poly(ethylene glycol) fumarate) hydrogels for guided tissue regeneration applications. J. Biomater. Sci. Polymer Edition, 14, 989–1004.
Brink, K. S., Yang, P. J. and Temenoff, J. S. 2009. Degradative properties and cytocompatibility of a mixed-mode hydrogel containing oligo[poly(ethylene glycol)fumarate] and poly(ethylene glycol)dithiol. Acta Biomater., 5, 570–9.
Temenoff, J. S., Shin, H., Conway, D. E., Engel, P. S. and Mikos, A. G. 2003. In vitro cytotoxicity of redox radical initiators for cross-linking of oligo(poly(ethylene glycol) fumarate) macromers. Biomacromolecules, 4, 1605–13.
Fisher, J. P., Lalani, Z., Bossano, C. M. et al. 2004. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model. J. Biomed. Mater. Res. A, 68, 428–38.
Jo, S., Shin, H. and Mikos, A. G. 2001. Modification of oligo(poly(ethylene glycol) fumarate) macromer with a GRGD peptide for the preparation of functionalized polymer networks. Biomacromolecules, 2, 255–61.
Shin, H., Jo, S. and Mikos, A. G. 2002. Modulation of marrow stromal osteoblast adhesion on biomimetic oligo[poly(ethylene glycol) fumarate] hydrogels modified with Arg–Gly–Asp peptides and a poly(ethyleneglycol) spacer. J. Biomed. Mater. Res., 61, 169–79.
Shin, H., Zygourakis, K., Farach-Carson, M. C., Yaszemski, M. J. and Mikos, A. G. 2004. Modulation of differentiation and mineralization of marrow stromal cells cultured on biomimetic hydrogels modified with Arg–Gly–Asp containing peptides. J. Biomed. Mater. Res. A, 69, 535–43.
Shin, H., Zygourakis, K., Farach-Carson, M. C., Yaszemski, M. J. and Mikos, A. G. 2004. Attachment, proliferation, and migration of marrow stromal osteoblasts cultured on biomimetic hydrogels modified with an osteopontin-derived peptide. Biomaterials, 25, 895–906.
Shin, H., Temenoff, J. S., Bowden, G. C. et al. 2005. Osteogenic differentiation of rat bone marrow stromal cells cultured on Arg–Gly–Asp modified hydrogels without dexamethasone and beta-glycerol phosphate. Biomaterials, 26, 3645–54.
Dadsetan, M., Hefferan, T. E., Szatkowski, J. P. et al. 2008. Effect of hydrogel porosity on marrow stromal cell phenotypic expression. Biomaterials, 29, 2193–202.
Park, H., Temenoff, J. S., Holland, T. A., Tabata, Y. and Mikos, A. G. 2005. Delivery of TGF-β1 and chondrocytes via injectable, biodegradable hydrogels for cartilage tissue engineering applications. Biomaterials, 26, 7095–103.
Park, H., Temenoff, J. S., Tabata, Y., Caplan, A. I. and Mikos, A. G. 2007. Injectable biodegradable hydrogel composites for rabbit marrow mesenchymal stem cell and growth factor delivery for cartilage tissue engineering. Biomaterials, 28, 3217–27.
Park, H., Temenoff, J. S., Tabata, Y. et al. 2009. Effect of dual growth factor delivery on chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in injectable hydrogel composites. J. Biomed. Mater. Res. A, 88, 889–97.
Guo, X., Liao, J., Park, H. et al. 2010. Effects of TGF-β3 and preculture period of osteogenic cells on the chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in a bilayered hydrogel composite. Acta Biomater., 6, 2920–31.
Guo, X., Park, H., Liu, G. et al. 2009. In vitro generation of an osteochondral construct using injectable hydrogel composites encapsulating rabbit marrow mesenchymal stem cells. Biomaterials, 30, 2741–52.
Holland, T. A., Bodde, E. W., Baggett, L. S. et al. 2005. Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds. J. Biomed. Mater. Res. A, 75, 156–67.
Holland, T. A., Bodde, E. W., Cuijpers, V. M. et al. 2007. Degradable hydrogel scaffolds for in vivo delivery of single and dual growth factors in cartilage repair. Osteoarthritis Cartilage, 15, 187–97.
Guo, X., Park, H., Young, S. et al. 2010. Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model. Acta Biomater., 6, 39–47.
Doroski, D. M., Levenston, M. E. and Temenoff, J. S. 2010. Cyclic tensile culture promotes fibroblastic differentiation of marrow stromal cells encapsulated in poly(ethylene glycol)-based hydrogels. Tissue Eng. Part A, 16, 3457–66.
Hammoudi, T. M., Lu, H. and Temenoff, J. S. 2010. Long-term spatially defined coculture within three-dimensional photopatterned hydrogels. Tissue Eng. Part C Methods, 16, 1621–8.
Zhang, M. W., Park, H., Guo, X. et al. 2010. Adapting biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels for pigment epithelial cell encapsulation and lens regeneration. Tissue Eng. Part C Methods, 16, 261–7.
Dadsetan, M., Knight, A. M., Lu, L., Windebank, A. J. and Yaszemski, M. J. 2009. Stimulation of neurite outgrowth using positively charged hydrogels. Biomaterials, 30, 3874–81.
Runge, M. B., Dadsetan, M., Baltrusaitis, J. et al. 2010. The development of electrically conductive polycaprolactone fumarate–polypyrrole composite materials for nerve regeneration. Biomaterials, 31, 5916–26.
Runge, M. B., Dadsetan, M., Baltrusaitis, J. et al. 2010. Development of electrically conductive oligo(polyethylene glycol) fumarate–polypyrrole hydrogels for nerve regeneration. Biomacromolecules, 11, 2845–53.
Wang, S., Yaszemski, M. J., Knight, A. M. et al. 2009. Photo-crosslinked poly(ε-caprolactone fumarate) networks for guided peripheral nerve regeneration: material properties and preliminary biological evaluations. Acta Biomater., 5, 1531–42.
Dadsetan, M., Liu, Z., Pumberger, M. et al. 2010. A stimuli-responsive hydrogel for doxorubicin delivery. Biomaterials, 31, 8051–62.
Rooney, G. E., Knight, A. M., Madigan, N. N. et al. 2011. Sustained delivery of dibutyryl cyclic adenosine monophosphate to the transected spinal cord via oligo[(polyethylene glycol) fumarate] hydrogels. Tissue Eng. Part A, 17, 1287–302.
Holland, T. A., Tabata, Y. and Mikos, A. G. 2005. Dual growth factor delivery from degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds for cartilage tissue engineering. J. Control. Release, 101, 111–25.
Dadsetan, M., Szatkowski, J. P., Shogren, K. L., Yaszemski, M. J. and Maran, A. 2009. Hydrogel-mediated DNA delivery confers estrogenic response in nonresponsive osteoblast cells. J. Biomed. Mater. Res. A, 91, 1170–7.
Kasper, F. K., Seidlits, S. K., Tang, A. et al. 2005. In vitro release of plasmid DNA from oligo(poly(ethylene glycol) fumarate) hydrogels. J. Control. Release, 104, 521–39.
Kasper, F. K., Jerkins, E., Tanahashi, K. et al. 2006. Characterization of DNA release from composites of oligo(poly(ethylene glycol) fumarate) and cationized gelatin microspheres in vitro. J. Biomed. Mater. Res. A, 78, 823–35.
Kasper, F. K., Kushibiki, T., Kimura, Y., Mikos, A. G. and Tabata, Y. 2005. In vivo release of plasmid DNA from composites of oligo(poly(ethylene glycol)fumarate) and cationized gelatin microspheres. J. Control. Release, 107, 547–61.
Kasper, F. K., Young, S., Tanahashi, K. et al. 2006. Evaluation of bone regeneration by DNA release from composites of oligo(poly(ethylene glycol) fumarate) and cationized gelatin microspheres in a critical-sized calvarial defect. J. Biomed. Mater. Res. A, 78, 335–42.
Sarvestani, A. S., Xu, W. J., He, X. Z. and Jabbari, E. 2007. Gelation and degradation characteristics of in situ photo-crosslinked poly(l-lactid-co-ethylene oxide-co-fumarate) hydrogels. Polymer, 48, 7113–20.
He, X., Ma, J. and Jabbari, E. 2010. Migration of marrow stromal cells in response to sustained release of stromal-derived factor-1α from poly(lactide ethylene oxide fumarate) hydrogels. Int. J. Pharm., 390, 107–16.
He, X., Ma, J. and Jabbari, E. 2008. Effect of grafting RGD and BMP-2 protein-derived peptides to a hydrogel substrate on osteogenic differentiation of marrow stromal cells. Langmuir, 24, 12508–16.
Sarvestani, A. S., He, X. and Jabbari, E. 2007. Effect of osteonectin-derived peptide on the viscoelasticity of hydrogel/apatite nanocomposite scaffolds. Biopolymers, 85, 370–8.
Sarvestani, A. S. and Jabbari, E. 2006. Modeling and experimental investigation of rheological properties of injectable poly(lactide ethylene oxide fumarate)/hydroxyapatite nanocomposites. Biomacromolecules, 7, 1573–80.
Xu, W., Ma, J. and Jabbari, E. 2010. Material properties and osteogenic differentiation of marrow stromal cells on fiber-reinforced laminated hydrogel nanocomposites. Acta Biomater., 6, 1992–2002.