Fabrication of sulphonated poly(ethylene glycol)-diacrylate hydrogel as a bone grafting scaffold

  • Hao Li
  • Tingting Ma
  • Man Zhang
  • Jiani Zhu
  • Jie Liu
  • Fei TanEmail author
Tissue Engineering Constructs and Cell Substrates Original Research
Part of the following topical collections:
  1. Tissue Engineering Constructs and Cell Substrates


To improve the biological performance of poly(ethylene glycol)-diacrylate (PEGDA) hydrogel as an injectable bone grafting scaffold, sodium methallyl sulphonate (SMAS) was incorporated into PEGDA hydrogel. The physiochemical properties of the resultant polymers were assessed via Fourier transform infrared spectroscopy (FTIR), swelling ratio, zeta potential, surface morphology, and protein adsorption analysis. MC3T3-E1 cells were seeded on the hydrogel to evaluate the effect of the sulphonated modification on their attachment, proliferation, and differentiation. The results of FTIR and zeta potential evaluations revealed that SMAS was successfully incorporated into PEGDA. With increasing concentrations of SMAS, the swelling ratio of the hydrogels increased in deionized water but stayed constant in phosphate buffered saline. The protein adsorption also increased with increasing concentration of SMAS. Moreover, the sulphonated modification of PEGDA hydrogel not only enhanced the attachment and proliferation of osteoblast-like MC3T3-E1 cells but also up-regulated alkaline phosphatase activity as well as gene expression of osteogenic markers and related growth factors, including collagen type I, osteocalcin, runt related transcription factor 2, bone morphogenetic protein 2, and transforming growth factor beta 1. These findings indicate that the sulphonated modification could significantly improve the biological performance of PEGDA hydrogel. Thus, the sulphonated PEGDA is a promising scaffold candidate for bone grafting.



This study was supported by Shandong Provincial Natural Science Foundation (ZR2018BH015).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Engberg K, Frank CW. Protein diffusion in photopolymerized poly(ethylene glycol) hydrogel networks. Biomed Mater. 2011;6:055006.CrossRefGoogle Scholar
  2. 2.
    Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32:773–85.CrossRefGoogle Scholar
  3. 3.
    Corbin EA, Millet LJ, Pikul JH, Johnson CL, Georgiadis JG, King WP. et al. Micromechanical properties of hydrogels measured with MEMS resonant sensors. Biomed Micro. 2013;15:311–9.CrossRefGoogle Scholar
  4. 4.
    Benoit DS, Schwartz MP, Durney AR, Anseth KS. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. Nat Mater. 2008;7:816–23.CrossRefGoogle Scholar
  5. 5.
    Schmidt S, Madaboosi N, Uhlig K, Kohler D, Skirtach A, Duschl C. et al. Control of cell adhesion by mechanical reinforcement of soft polyelectrolyte films with nanoparticles. Langmuir. 2012;28:7249–57.CrossRefGoogle Scholar
  6. 6.
    Sun K, Liu H, Wang S, Jiang L. Cytophilic/cytophobic design of nanomaterials at biointerfaces. Small. 2013;9:1444–8.CrossRefGoogle Scholar
  7. 7.
    Saxena S, Spears MW Jr., Yoshida H, Gaulding JC, Garcia AJ, Lyon LA. Microgel film dynamics modulate cell adhesion behavior. Soft Matter. 2014;10:1356–64.CrossRefGoogle Scholar
  8. 8.
    Pham MT, Reuther H, Maitz MF. Native extracellular matrix coating on Ti surfaces. J Biomed Mater Res A. 2003;66:310–6.CrossRefGoogle Scholar
  9. 9.
    Lehnert M, Gorbahn M, Rosin C, Klein M, Koper I, Al-Nawas B. et al. Adsorption and conformation behavior of biotinylated fibronectin on streptavidin-modified TiO(X) surfaces studied by SPR and AFM. Langmuir. 2011;27:7743–51.CrossRefGoogle Scholar
  10. 10.
    Felgueiras HP, Evans MD, Migonney V. Contribution of fibronectin and vitronectin to the adhesion and morphology of MC3T3-E1 osteoblastic cells to poly(NaSS) grafted Ti6Al4V. Acta Biomater. 2015;28:225–33.CrossRefGoogle Scholar
  11. 11.
    Tan F, Xu X, Deng T, Yin M, Zhang X, Wang J. Fabrication of positively charged poly(ethylene glycol)-diacrylate hydrogel as a bone tissue engineering scaffold. Biomed Mater. 2012;7:055009.CrossRefGoogle Scholar
  12. 12.
    Dadsetan M, Pumberger M, Casper ME, Shogren K, Giuliani M, Ruesink T. et al. The effects of fixed electrical charge on chondrocyte behavior. Acta Biomater. 2011;7:2080–90.CrossRefGoogle Scholar
  13. 13.
    Nakamura S, Kobayashi T, Nakamura M, Itoh S, Yamashita K. Electrostatic surface charge acceleration of bone ingrowth of porous hydroxyapatite/beta-tricalcium phosphate ceramics. J Biomed Mater Res A. 2010;92:267–75.CrossRefGoogle Scholar
  14. 14.
    Li H, Ji Q, Chen X, Sun Y, Xu Q, Deng P. et al. Accelerated bony defect healing based on chitosan thermosensitive hydrogel scaffolds embedded with chitosan nanoparticles for the delivery of BMP2 plasmid DNA. J Biomed Mater Res A. 2017;105:265–73.CrossRefGoogle Scholar
  15. 15.
    Pernodet N, Rafailovich M, Sokolov J, Xu D, Yang NL, McLeod K. Fibronectin fibrillogenesis on sulfonated polystyrene surfaces. J Biomed Mater Res A. 2003;64:684–92.CrossRefGoogle Scholar
  16. 16.
    Keselowsky BG, Collard DM, Garcia AJ. Surface chemistry modulates fibronectin conformation and directs integrin binding and specificity to control cell adhesion. J Biomed Mater Res A. 2003;66:247–59.CrossRefGoogle Scholar
  17. 17.
    Hartvig RA, van de Weert M, Ostergaard J, Jorgensen L, Jensen H. Protein adsorption at charged surfaces: the role of electrostatic interactions and interfacial charge regulation. Langmuir. 2011;27:2634–43.CrossRefGoogle Scholar
  18. 18.
    Lou T, Wang X, Song G, Gu Z, Yang Z. Fabrication of PLLA/beta-TCP nanocomposite scaffolds with hierarchical porosity for bone tissue engineering. Int J Biol Macromol. 2014;69:464–70.CrossRefGoogle Scholar
  19. 19.
    Saha K, Pollock JF, Schaffer DV, Healy KE. Designing synthetic materials to control stem cell phenotype. Curr Opin Chem Biol. 2007;11:381–7.CrossRefGoogle Scholar
  20. 20.
    Cartmell SH, Thurstan S, Gittings JP, Griffiths S, Bowen CR, Turner IG. Polarization of porous hydroxyapatite scaffolds: influence on osteoblast cell proliferation and extracellular matrix production. J Biomed Mater Res A. 2014;102:1047–52.CrossRefGoogle Scholar
  21. 21.
    Anderson DG, Levenberg S, Langer R. Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat Biotechnol. 2004;22:863–6.CrossRefGoogle Scholar
  22. 22.
    Bacakova L, Filova E, Parizek M, Ruml T, Svorcik V. Modulation of cell adhesion, proliferation and differentiation on materials designed for body implants. Biotechnol Adv. 2011;29:739–67.CrossRefGoogle Scholar
  23. 23.
    Nuttelman CR, Benoit DS, Tripodi MC, Anseth KS. The effect of ethylene glycol methacrylate phosphate in PEG hydrogels on mineralization and viability of encapsulated hMSCs. Biomaterials. 2006;27:1377–86.CrossRefGoogle Scholar
  24. 24.
    Itoh S, Nakamura S, Kobayashi T, Shinomiya K, Yamashita K, Itoh S. Effect of electrical polarization of hydroxyapatite ceramics on new bone formation. Calcif Tissue Int. 2006;78:133–42.CrossRefGoogle Scholar
  25. 25.
    Wang X, Lou T, Zhao W, Song G, Li C, Cui G. The effect of fiber size and pore size on cell proliferation and infiltration in PLLA scaffolds on bone tissue engineering. J Biomater Appl. 2016;30:1545–51.CrossRefGoogle Scholar
  26. 26.
    Lou T, Wang X, Song G, Gu Z, Yang Z. Structure and properties of PLLA/beta-TCP nanocomposite scaffolds for bone tissue engineering. J Mater Sci Mater Med. 2015;26:5366.CrossRefGoogle Scholar
  27. 27.
    Olabisi RM, Lazard ZW, Franco CL, Hall MA, Kwon SK, Sevick-Muraca EM. et al. Hydrogel microsphere encapsulation of a cell-based gene therapy system increases cell survival of injected cells, transgene expression, and bone volume in a model of heterotopic ossification. Tissue Eng Part A. 2010;16:3727–36.CrossRefGoogle Scholar
  28. 28.
    Hassan W, Dong Y, Wang W. Encapsulation and 3D culture of human adipose-derived stem cells in an in-situ crosslinked hybrid hydrogel composed of PEG-based hyperbranched copolymer and hyaluronic acid. Stem Cell Res Ther. 2013;4:32.CrossRefGoogle Scholar
  29. 29.
    Felgueiras HP, Decambron A, Manassero M, Tulasne L, Evans MD, Viateau V, Migonney V. Bone tissue response induced by bioactive polymer functionalized Ti6Al4V surfaces: in vitro and in vivo study. J Colloid Interface Sci. 2017;491:44–54.CrossRefGoogle Scholar
  30. 30.
    Tibbitt MW, Rodell CB, Burdick JA, Anseth KS. Progress in material design for biomedical applications. Proc Natl Acad Sci USA. 2015;112:14444–51.CrossRefGoogle Scholar
  31. 31.
    Rath B, Nam J, Knobloch TJ, Lannutti JJ, Agarwal S. Compressive forces induce osteogenic gene expression in calvarial osteoblasts. J Biomech. 2008;41:1095–103.CrossRefGoogle Scholar
  32. 32.
    Sharma B, Fermanian S, Gibson M, Unterman S, Herzka DA, Cascio B. et al. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci Transl Med. 2013;5:167ra6CrossRefGoogle Scholar
  33. 33.
    Hao W, Jiang C, Jiang M, Wang T, Wang X. Osteogenic potency of dedifferentiated fat cells isolated from elderly people with osteoporosis. Exp Ther Med. 2017;14:43–50.CrossRefGoogle Scholar
  34. 34.
    Yang X, Yang K, Liao L, Jin Y. [Effect of miR-705 on osteogenic differentiation of mouse embryo osteoblast precursor cells MC3T3-E1]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2016;45:575–80.Google Scholar
  35. 35.
    Marsh BC, Kerr NC, Isles N, Denhardt DT, Wynick D. Osteopontin expression and function within the dorsal root ganglion. Neuroreport. 2007;18:153–7.CrossRefGoogle Scholar
  36. 36.
    Wang D, Wang H, Gao F, Wang K, Dong F. ClC-3 promotes osteogenic differentiation in MC3T3-E1 cell after dynamic compression. J Cell Biochem. 2017;118:1606–13.CrossRefGoogle Scholar
  37. 37.
    Yao KL, Todescan R Jr., Sodek J. Temporal changes in matrix protein synthesis and mRNA expression during mineralized tissue formation by adult rat bone marrow cells in culture. J Bone Miner Res. 1994;9:231–40.CrossRefGoogle Scholar
  38. 38.
    Chen CH, Chang CH, Wang KC, Su CI, Liu HT, Yu CM. et al. Enhancement of rotator cuff tendon-bone healing with injectable periosteum progenitor cells-BMP-2 hydrogel in vivo. Knee Surg Sports Traumatol Arthrosc. 2011;19:1597–607.CrossRefGoogle Scholar
  39. 39.
    Canalis E, Economides AN, Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev. 2003;24:218–35.CrossRefGoogle Scholar
  40. 40.
    Shibata Y, Abiko Y, Moriya Y, Yoshida W, Takiguchi H. Effects of transforming growth factor-beta on collagen gene expression and collagen synthesis level in mineralizing cultures of osteoblast-like cell line, MC3T3-E1. Int J Biochem. 1993;25:239–45.CrossRefGoogle Scholar
  41. 41.
    Hughes FJ, Turner W, Belibasakis G, Martuscelli G. Effects of growth factors and cytokines on osteoblast differentiation. Periodontol 2000. 2006;41:48–72.CrossRefGoogle Scholar
  42. 42.
    Takahashi Y, Yamamoto M, Tabata Y. Enhanced osteoinduction by controlled release of bone morphogenetic protein-2 from biodegradable sponge composed of gelatin and beta-tricalcium phosphate. Biomaterials. 2005;26:4856–65.CrossRefGoogle Scholar
  43. 43.
    Chiang CW, Chen WC, Liu HW, Wang IC, Chen CH. Evaluating osteogenic potential of ligamentum flavum cells cultivated in photoresponsive hydrogel that incorporates bone morphogenetic protein-2 for spinal fusion. Int J Mol Sci. 2015;16:23318–36.CrossRefGoogle Scholar
  44. 44.
    Jeon EJ, Lee KY, Choi NS, Lee MH, Kim HN, Jin YH. et al. Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem. 2006;281:16502–11.CrossRefGoogle Scholar
  45. 45.
    Gersbach CA, Byers BA, Pavlath GK, Garcia AJ. Runx2/Cbfa1 stimulates transdifferentiation of primary skeletal myoblasts into a mineralizing osteoblastic phenotype. Exp Cell Res. 2004;300:406–17.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Prosthodontics, the Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdaoPeople’s Republic of China

Personalised recommendations