Skip to main content

Advertisement

SpringerLink
Log in

Cell-laden photocrosslinked GelMA–DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

To effectively repair or replace damaged tissues, it is necessary to design three dimensional (3D) extracellular matrix (ECM) mimicking scaffolds with tunable biomechanical properties close to the desired tissue application. In the present work, gelatin methacrylate (GelMA) and dextran glycidyl methacrylate (DexMA) with tunable mechanical and biological properties were utilized to prepared novel bicomponent polymeric hydrogels by cross-linking polymerization using photoinitiation. We controlled the degree of substitution (DS) of glycidyl methacrylate in DexMA so that they could obtain relevant mechanical properties. The results indicated that copolymer hydrogels demonstrated a lower swelling ratio and higher compressive modulus as compared to the GelMA. Moreover, all of the hydrogels exhibited a honeycomb-like architecture, the pore sizes decreased as DS increased, and NIH-3T3 fibroblasts encapsulated in these hydrogels all exhibited excellent viability. These characteristics suggest a class of photocrosslinkable, tunable mechanically copolymer hydrogels that may find potential application in tissue engineering and regenerative medicine applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Li Y, Rodrigues J, Tomas H. Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applications. Chem Soc Rev. 2012;41(6):2193–221.

    Article  Google Scholar 

  2. Kopecek J. Hydrogel biomaterials: a smart future? Biomaterials. 2007;28(34):5185–92.

    Article  Google Scholar 

  3. Ifkovits JL, Burdick JA. Review: photopolymerizable and degradable biomaterials for tissue engineering applications. Tissue Eng. 2007;13(10):2369–85.

    Article  Google Scholar 

  4. Xiao W, He J, Nichol JW, Wang L, Hutson CB, Wang B, et al. Synthesis and characterization of photocrosslinkable gelatin and silk fibroin interpenetrating polymer network hydrogels. Acta Biomater. 2011;7(6):2384–93.

    Article  Google Scholar 

  5. Suri S, Schmidt CE. Photopatterned collagen-hyaluronic acid interpenetrating polymer network hydrogels. Acta Biomater. 2009;5(7):2385–97.

    Article  Google Scholar 

  6. Chen MB, Srigunapalan S, Wheeler AR, Simmons CA. A 3D microfluidic platform incorporating methacrylated gelatin hydrogels to study physiological cardiovascular cell–cell interactions. Lab Chip. 2013;13(13):2591–8.

    Article  Google Scholar 

  7. Yang Y, Tang H, Kowitsch A, Mader K, Hause G, Ulrich J, et al. Novel mineralized heparin-gelatin nanoparticles for potential application in tissue engineering of bone. J Mater Sci Mater Med. 2014;25(3):669–80.

    Google Scholar 

  8. Hu X, Li D, Gao C. Chemically cross-linked chitosan hydrogel loaded with gelatin for chondrocyte encapsulation. Biotechnol J. 2011;6(11):1388–96.

    Article  Google Scholar 

  9. Aubin H, Nichol JW, Hutson CB, Bae H, Sieminski AL, Cropek DM, et al. Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials. 2010;31(27):6941–51.

    Article  Google Scholar 

  10. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials. 2010;31(21):5536–44.

    Article  Google Scholar 

  11. Kim SH, Chu CC. Synthesis and characterization of dextran–methacrylate hydrogels and structural study by SEM. J Biomed Mater Res. 2000;49(4):517–27.

    Article  Google Scholar 

  12. Yin R, Wang K, Han J, Nie J. Photo-crosslinked glucose-sensitive hydrogels based on methacrylate modified dextran–concanavalin A and PEG dimethacrylate. Carbohydr Polym. 2010;82(2):412–8.

    Article  Google Scholar 

  13. Chen FM, Zhao YM, Sun HH, Jin T, Wang QT, Zhou W, et al. Novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hydrogel scaffolds containing microspheres loaded with bone morphogenetic proteins: formulation and characteristics. J Controlled Release. 2007;118(1):65–77.

    Article  Google Scholar 

  14. Sun G, Shen YI, Ho CC, Kusuma S, Gerecht S. Functional groups affect physical and biological properties of dextran-based hydrogels. J Biomed Mater Res A. 2010;93(3):1080–90.

    Google Scholar 

  15. Liu Y, Chan-Park MB. Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering. Biomaterials. 2009;30(2):196–207.

    Article  Google Scholar 

  16. Pescosolido L, Vermonden T, Malda J, Censi R, Dhert WJ, Alhaique F, et al. In situ forming IPN hydrogels of calcium alginate and dextran-HEMA for biomedical applications. Acta Biomater. 2011;7(4):1627–33.

    Article  Google Scholar 

  17. Shin H, Olsen BD, Khademhosseini A. The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules. Biomaterials. 2012;33(11):3143–52.

    Article  Google Scholar 

  18. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101(7):1869–80.

    Article  Google Scholar 

  19. Shin SR, Bae H, Cha JM, Mun JY, Chen Y-C, Tekin H, et al. Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation. ACS Nano. 2011;6(1):362–72.

    Article  Google Scholar 

  20. Coutinho DF, Sant SV, Shin H, Oliveira JT, Gomes ME, Neves NM, et al. Modified Gellan Gum hydrogels with tunable physical and mechanical properties. Biomaterials. 2010;31(29):7494–502.

    Article  Google Scholar 

  21. Ribeiro MP, Morgado PI, Miguel SP, Coutinho P, Correia IJ. Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing. Mater Sci Eng C. 2013;33(5):2958–66.

    Article  Google Scholar 

  22. Shin SR, Jung SM, Zalabany M, Kim K, Zorlutuna P, Kim SB, et al. Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. ACS Nano. 2013;7(3):2369–80.

    Article  Google Scholar 

  23. Van Vlierberghe S, Cnudde V, Dubruel P, Masschaele B, Cosijns A, De Paepe I, et al. Porous gelatin hydrogels: 1. Cryogenic formation and structure analysis. Biomacromolecules. 2007;8(2):331–7.

    Article  Google Scholar 

  24. Dubruel P, Unger R, Van Vlierberghe S, Cnudde V, Jacobs PJ, Schacht E, et al. Porous gelatin hydrogels: 2. In vitro cell interaction study. Biomacromolecules. 2007;8(2):338–44.

    Article  Google Scholar 

  25. Bae H, Ahari AF, Shin H, Nichol JW, Hutson CB, Masaeli M, et al. Cell-laden microengineered pullulan methacrylate hydrogels promote cell proliferation and 3D cluster formation. Soft Matter. 2011;7(5):1903–11.

    Article  Google Scholar 

  26. Phull MK, Eydmann T, Roxburgh J, Sharpe JR, Lawrence-Watt DJ, Phillips G, et al. Novel macro-microporous gelatin scaffold fabricated by particulate leaching for soft tissue reconstruction with adipose-derived stem cells. J Mater Sci Mater Med. 2013;24(2):461–7.

    Google Scholar 

  27. Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJ, Hutmacher DW, et al. Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs. Macromol Biosci. 2013;13(5):551–61.

    Article  Google Scholar 

  28. Chan V, Zorlutuna P, Jeong JH, Kong H, Bashir R. Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation. Lab Chip. 2010;10(16):2062–70.

    Article  Google Scholar 

  29. Chen YC, Lin RZ, Qi H, Yang Y, Bae H, Melero-Martin JM, et al. Functional human vascular network generated in photocrosslinkable gelatin methacrylate hydrogels. Adv Funct Mater. 2012;22(10):2027–39.

    Article  Google Scholar 

  30. Gómez-Guillén MC, Giménez B, López-Caballero ME, Montero MP. Functional and bioactive properties of collagen and gelatin from alternative sources: a review. Food Hydrocoll. 2011;25(8):1813–27.

    Article  Google Scholar 

  31. Liao H, Zhang H, Chen W. Differential physical, rheological, and biological properties of rapid in situ gelable hydrogels composed of oxidized alginate and gelatin derived from marine or porcine sources. J Mater Sci Mater Med. 2009;20(6):1263–71.

    Google Scholar 

  32. Dragusin D-M, Van Vlierberghe S, Dubruel P, Dierick M, Van Hoorebeke L, Declercq HA, et al. Novel gelatin–PHEMA porous scaffolds for tissue engineering applications. Soft Matter. 2012;8(37):9589.

    Article  Google Scholar 

  33. Camci-Unal G, Aubin H, Ahari AF, Bae H, Nichol JW, Khademhosseini A. Surface-modified hyaluronic acid hydrogels to capture endothelial progenitor cells. Soft Matter. 2010;6(20):5120–6.

    Article  Google Scholar 

  34. Boere KW, Visser J, Seyednejad H, Rahimian S, Gawlitta D, van Steenbergen MJ, et al. Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs. Acta Biomaterialia. 2014;10(6):2602–11.

    Article  Google Scholar 

  35. Slaughter BV, Khurshid SS, Fisher OZ, Khademhosseini A, Peppas NA. Hydrogels in regenerative medicine. Adv Mater. 2009;21(32–33):3307–29.

    Article  Google Scholar 

  36. Seliktar D. Designing cell-compatible hydrogels for biomedical applications. Science. 2012;336(6085):1124–8.

    Article  Google Scholar 

  37. Cha C, Soman P, Zhu W, Nikkhah M, Camci-Unal G, Chen S, et al. Structural reinforcement of cell-laden hydrogels with microfabricated three dimensional scaffolds. Biomater Sci. 2014;2(5):703.

    Article  Google Scholar 

  38. Haque MA, Kurokawa T, Gong JP. Super tough double network hydrogels and their application as biomaterials. Polymer. 2012;53(9):1805–22.

    Article  Google Scholar 

  39. Levental I, Georges PC, Janmey PA. Soft biological materials and their impact on cell function. Soft Matter. 2007;3(3):299.

    Article  Google Scholar 

  40. Wei YN, Wang QQ, Gao TT, Kong M, Yang KK, An Y, et al. 3-D culture of human umbilical vein endothelial cells with reversible thermosensitive hydroxybutyl chitosan hydrogel. J Mater Sci Mater Med. 2013;24(7):1781–7.

    Google Scholar 

  41. Hutson CB, Nichol JW, Aubin H, Bae H, Yamanlar S, Al-Haque S, et al. Synthesis and characterization of tunable poly(ethylene glycol): gelatin methacrylate composite hydrogels. Tissue Eng Part A. 2011;17(13–14):1713–23.

    Article  Google Scholar 

  42. Kumar PT, Srinivasan S, Lakshmanan VK, Tamura H, Nair SV, Jayakumar R. Synthesis, characterization and cytocompatibility studies of alpha-chitin hydrogel/nano hydroxyapatite composite scaffolds. Int J Biol Macromol. 2011;49(1):20–31.

    Article  Google Scholar 

  43. Hu X, Ma L, Wang C, Gao C. Gelatin hydrogel prepared by photo-initiated polymerization and loaded with TGF-beta1 for cartilage tissue engineering. Macromol Biosci. 2009;9(12):1194–201.

    Article  Google Scholar 

  44. Koshy ST, Ferrante TC, Lewin SA, Mooney DJ. Injectable, porous, and cell-responsive gelatin cryogels. Biomaterials. 2014;35(8):2477–87.

    Article  Google Scholar 

  45. Shin SR, Aghaei-Ghareh-Bolagh B, Dang TT, Topkaya SN, Gao X, Yang SY, et al. Cell-laden microengineered and mechanically tunable hybrid hydrogels of gelatin and graphene oxide. Adv Mater. 2013;25(44):6385–91.

    Article  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the financial support of National Key Basic Research Program of China (Grant No. 2012CB619100) and the National Natural Science Foundation of China (Grant No. 51372087, 51072057).

Author information

Authors and Affiliations

  1. School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China

    Hang Wang, Lei Zhou, Ying Tan, Kongyou Ouyang & Guoxin Tan

  2. College of Materials Science and Technology, South China University of Technology, Guangzhou, 510641, China

    Lei Zhou, Jingwen Liao & Chenyun Ning

  3. Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Guoxin Ni

Authors
  1. Hang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jingwen Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kongyou Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chenyun Ning
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Guoxin Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guoxin Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Chenyun Ning or Guoxin Tan.

Additional information

Lei Zhou equal first author

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Zhou, L., Liao, J. et al. Cell-laden photocrosslinked GelMA–DexMA copolymer hydrogels with tunable mechanical properties for tissue engineering. J Mater Sci: Mater Med 25, 2173–2183 (2014). https://doi.org/10.1007/s10856-014-5261-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-014-5261-x

Keywords

Search

Navigation