Skip to main content
Log in

Alginate-honey bioinks with improved cell responses for applications as bioprinted tissue engineered constructs

  • Article
  • Published:
Journal of Materials Research Aims and scope Submit manuscript

Abstract

The polysaccharide alginate has received most extensive attention as bioink in bioprinting applications due to its ability to undergo gelation under cell-friendly conditions. However, absence of cell-binding motifs and the erratic degradation of alginate hydrogels have remained their persistent limitations. Honey is a conveniently available natural material, known for its role in wound healing and skin tissue regeneration. However, honey blending to improve biological response of alginate-based bioprinted scaffolds has not been yet reported. In the present work, honey-alginate bioinks were evaluated for their printability property (shape fidelity). It was found that honey blending reduced alginate viscosity, which gradually affected bioprinting fidelity. Therefore, the concentration that provides for acceptable bioprinting along with improvement in cell proliferations is determined. It is concluded that honey blending improves cell response of alginate bioinks and can be a facile approach to obtain bioinks especially for in situ skin tissue engineering applications.

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

Access this article

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

Instant access to the full article PDF.

FIG. 1
FIG. 2
FIG. 3
FIG. 4
FIG. 5
FIG. 6
FIG. 7
FIG. 8

Similar content being viewed by others

References

  1. S. Bose, D. Ke, H. Sahasrabudhe, and A. Bandyopadhyay: Additive manufacturing of biomaterials. Prog. Mater. Sci. 93, 45 (2018).

    Google Scholar 

  2. I.T. Ozbolat, W. Pemg, and V. Ozbolat: Application areas of 3D bioprinting. Drug Discov. Today 21, 1257 (2017).

    Google Scholar 

  3. P.F. Egan, V.C. Gonella, M. Engensperger, S.J. Ferguson, and K. Shea: Computationally designed lattices with tuned properties for tissue engineering using 3D printing. PLoS One 12, e0182902 (2017).

    Google Scholar 

  4. W. Peng, P. Datta, B. Ayan, V. Ozbolat, D. Sosnoski, and I.T. Ozbolat: 3D bioprinting for drug discovery and development in pharmaceutics. Acta Biomater. 57, 26 (2017).

    CAS  Google Scholar 

  5. L. Ning and X. Chen: A brief review of extrusion-based tissue scaffold bio-printing. Biotechnol. J. 12, 1600671 (2017).

    Google Scholar 

  6. I.T. Ozbolat and M. Hospodiuk: Current advances and future perspectives in extrusion-based bioprinting. Biomaterials 76, 321 (2016).

    CAS  Google Scholar 

  7. N. Cubo, M. Garcia, J.F. Cañizo, D. Velasco, and J.L. Jorcano: 3D bioprinting of functional human skin: Production and in vivo analysis. Biofabrication 9 (2016).

  8. S. Duchi, C. Onofrillo, C.D.O. Connell, R. Blanchard, A.F. Quigle, R.M.I. Kapsa, P. Peter, G. Wallace, C. Di Bella, and P.F.M. Choong: Handheld co-axial bioprinting: Application to in situ surgical cartilage repair. Sci. Rep. 7, 5837 (2017).

    Google Scholar 

  9. K.W. Binder, W. Zhao, T. Aboushwareb, D. Dice, A. Atala, and J.J. Yoo: In situ bioprinting of the skin for burns. J. Am. Coll. Surg. 211, S76 (2010).

    Google Scholar 

  10. M. Hospodiuk, M. Dey, D. Sosnoski, and I.T. Ozbolat: The bioink: A comprehensive review on bioprintable materials. Biotechnol. Adv. 35, 217 (2017).

    CAS  Google Scholar 

  11. S.K. Williams and J.B. Hoying: Bioinks for bioprinting. In Bioprinting in Regenerative Medicine, K. Turksen, ed. (Springer International Publishing, Cham, 2015); pp. 1–31.

    Google Scholar 

  12. K. Hölzl, S. Lin, L. Tytgat, S. Van Vlierberghe, L. Gu, and A. Ovsianikov: Bioink properties before, during and after 3D bioprinting. Biofabrication 8, 032002 (2016).

    Google Scholar 

  13. A. Abbadessa, M.M. Blokzijl, V.H.M. Mouser, P. Marica, J. Malda, W.E. Hennink, and T. Vermonden: A thermo-responsive and photo-polymerizable chondroitin sulfate-based hydrogel for 3D printing applications. Carbohydr. Polym. 149, 163 (2016).

    CAS  Google Scholar 

  14. T. Billiet, M. Vandenhaute, J. Schelfhout, S. Vlierberghe, and P. Dubruel: A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 33, 6020–6041 (2012).

    CAS  Google Scholar 

  15. Z. Wu, X. Su, Y. Xu, B. Kong, W. Sun, and S. Mi: Bioprinting three-dimensional cell-laden tissue constructs with controllable degradation. Sci. Rep. 6, 24474 (2016).

    CAS  Google Scholar 

  16. J. Jia, D.J. Richards, S. Pollard, Y. Tan, J. Rodriguez, R.P. Visconti, T.C. Trusk, M.J. Yost, H. Yao, R.R. Markwald, and Y. Mei: Engineering alginate as bioink for bioprinting. Acta Biomater. 10, 4323 (2014).

    CAS  Google Scholar 

  17. Y. Luo, G. Luo, M. Gelinsky, P. Huang, and C. Ruan: 3D bioprinting scaffold using alginate/polyvinyl alcohol bioinks. Mater. Lett. 189, 295 (2017).

    CAS  Google Scholar 

  18. L.Q. Wan, J. Jiang, D.E. Arnold, X.E. Guo, H.H. Lu, and V.C. Mow: Calcium concentration effects on the mechanical and biochemical properties of chondrocyte-alginate constructs. Cell. Mol. Bioeng. 1, 93 (2008).

    CAS  Google Scholar 

  19. L. Vandamme, A. Heyneman, H. Hoeksema, J. Verbelen, and S. Monstrey: Honey in modern wound care: A systematic review. Burns 39, 1514 (2013).

    CAS  Google Scholar 

  20. S.K. Saikaly and A. Khachemoune: Honey and wound healing: An update. Am. J. Clin. Dermatol. 18, 237 (2017).

    Google Scholar 

  21. R.F. El-kased, R.I. Amer, D. Attia, and M.M. Elmazar: Honey-based hydrogel: In vitro and comparative in vivo evaluation for burn wound healing. Sci. Rep. 7, 9692 (2017).

    Google Scholar 

  22. D.S. Choi, S. Kim, Y. Lim, H. Gwon, J.S. Park, Y. Nho, J. Kwon, and C. Honey: Hydrogel incorporated with chestnut honey accelerates wound healing and promotes early HO-1 protein expression in diabetic (db/db) mice. Tissue Eng. Regener. Med. 9, 36 (2012).

    CAS  Google Scholar 

  23. J. Majtan: Honey: An immunomodulator in wound healing. Wound Repair Regen. 22, 187 (2014).

    Google Scholar 

  24. T. Wang, X.K. Zhu, X.T. Xue, and D.Y. Wu: Hydrogel sheets of chitosan, honey and gelatin as burn wound dressings. Carbohydr. Polym. 88, 75 (2012).

    CAS  Google Scholar 

  25. W.A. Sarhan and H.M.E. Azzazy: High concentration honey chitosan electrospun nanofibers: Biocompatibility and antibacterial effects. Carbohydr. Polym. 122, 135 (2015).

    CAS  Google Scholar 

  26. J. Tavakoli and Y. Tang: Honey/PVA hybrid wound dressings with controlled release of antibiotics: Structural, physico-mechanical and in-vitro biomedical studies. Mater. Sci. Eng., C 77, 318 (2017).

    CAS  Google Scholar 

  27. A. Chaudhury, S. Bag, A. Barui, P. Banerjee, and J. Chatterjee: Honey dilution impact on in vitro wound healing: Normoxic and hypoxic condition. Wound Repair Regen. 23, 412 (2015).

    Google Scholar 

  28. L. Wang, M. Xu, L. Luo, Y. Zhou, and P. Si: Iterative feedback bio-printing-derived cell-laden hydrogel scaffolds with optimal geometrical fidelity and cellular controllability. Sci. Rep. 8, 2802 (2018).

    Google Scholar 

  29. A. Ribeiro, M.M. Blokzijl, R. Levato, C.W. Visser, M. Castilho, W.E. Hennink, T. Vermonden, and J. Malda: Assessing bioink shape fidelity to aid material development in 3D bioprinting. Biofabrication 10, 014102 (2017).

    CAS  Google Scholar 

  30. L. Ouyang, C.B. Highley, C.B. Rodell, W. Sun, and J.A. Burdick: 3D printing of shear-thinning hyaluronic acid hydrogels with secondary cross-linking. ACS Biomater. Sci. Eng. 2, 1743 (2016).

    CAS  Google Scholar 

  31. L. Ouyang, R. Yao, Y. Zhao, and W. Sun: Effect of bioink properties on printability and cell viability for 3D bioplotting of embryonic stem cells. Biofabrication 8, 035020 (2016).

    Google Scholar 

  32. S. Kyle, Z.M. Jessop, A. Al-sabah, and I.S. Whitaker: “Printability” of candidate biomaterials for extrusion based 3D printing: State-of-the-art. Adv. Healthcare Mater. 6, 1700264 (2017).

    Google Scholar 

  33. M. Di Giuseppe, N. Law, B. Webb, R.A. Macrae, L.J. Liew, T.B. Sercombe, R.J. Dilley, and B.J. Doyle: Mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting. J. Mech. Behav. Biomed. Mater. 79, 150 (2018).

    Google Scholar 

  34. K.R. Hixon, T. Lu, M.N. Carletta, S.H. McBride-Gagyi, B.E. Janowiak, and S.A. Sell: A preliminary in vitro evaluation of the bioactive potential of cryogel scaffolds incorporated with Manuka honey for the treatment of chronic bone infections. J. Biomed. Mater. Res., Part B 106, 1918–1933 (2017).

    Google Scholar 

  35. R. Sarkar, A. Ghosh, A. Barui, and P. Datta: Repositing honey incorporated electrospun nanofiber membranes to provide anti-oxidant, anti-bacterial and anti-inflammatory microenvironment for wound regeneration. J. Mater. Sci.: Mater. Med. 29, 31 (2018).

    Google Scholar 

  36. Y. He, F. Yang, H. Zhao, Q. Gao, B. Xia, and J. Fu: Research on the printability of hydrogels in 3D bioprinting. Sci. Rep. 6, 1 (2016).

    Google Scholar 

  37. A. Schmitt, P. Rödel, C. Anamur, C. Seeliger, A.B. Imhoff, E. Herbst, S. Vogt, M. Van Griensven, G. Winter, and J. Engert: Calcium alginate gels as stem cell matrix-making paracrine stem cell activity available for enhanced healing after surgery. PLoS One 10, 1 (2015).

    Google Scholar 

  38. B.E. Larsen, J. Bjørnstad, E.O. Pettersen, H.H. Tønnesen, and J.E. Melvik: Rheological characterization of an injectable alginate gel system. BMC Biotechnol. 15, 1 (2015).

    Google Scholar 

  39. J.H.Y. Chung, S. Naficy, Z. Yue, R. Kapsa, A. Quigley, S.E. Moulton, and G.G. Wallace: Bio-ink properties and printability for extrusion printing living cells. Biomater. Sci. 1, 763 (2013).

    CAS  Google Scholar 

  40. J. Park, S.J. Lee, S. Chung, J.H. Lee, W.D. Kim, J.Y. Lee, and S.A. Park: Cell-laden 3D bioprinting hydrogel matrix depending on different compositions for soft tissue engineering: Characterization and evaluation. Mater. Sci. Eng., C 71, 678 (2017).

    CAS  Google Scholar 

  41. M. Di Giuseppe, N. Law, B. Webb, R.A. Macrae, T.B. Sercombe, R.J. Dilley, B.J. Doyle, and L.J. Liew: Journal of the mechanical behavior of biomedical materials mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting. J. Mech. Behav. Biomed. Mater. 79, 150 (2018).

    Google Scholar 

  42. G. Kaklamani, D. Cheneler, L.M. Grover, M.J. Adams, and J. Bowen: Mechanical properties of alginate hydrogels manufactured using external gelation. J. Mech. Behav. Biomed. Mater. 36, 135 (2014).

    CAS  Google Scholar 

  43. M. Ahearne, Y. Yang, and K. Liu: Mechanical characterisation of hydrogels for tissue engineering applications. Tissue Eng. 4, 1 (2008).

    Google Scholar 

  44. K.R. Hixon, T. Lu, S.H. McBride-Gagyi, B.E. Janowiak, and S.A. Sell: A comparison of tissue engineering scaffolds incorporated with manuka honey of varying UMF. BioMed Res. Int. 2017, 4843065 (2017).

    Google Scholar 

  45. B.A. Minden-Birkenmaier, R.M. Neuhalfen, B.E. Janowiak, and S. Sell: Preliminary investigation and characterization of electrospun polycaprolactone and manuka honey scaffolds for dermal repair. J. Eng. Fibers Fabr. 10, 126 (2015).

    CAS  Google Scholar 

  46. M. Rajput, N. Bhandaru, A. Barui, A. Chaudhary, R.R. Paul, R. Mukherjee, and J. Chatterjee: Nano-patterned honey incorporated silk fibroin membranes for improving cellular compatibility. RSC Adv. 4, 44674 (2014).

    CAS  Google Scholar 

  47. M. Funada, H. Hara, H. Sasagawa, Y. Kitagawa, and T. Kadowaki: A honey bee Dscam family member, AbsCAM, is a brain-specific cell adhesion molecule with the neurite outgrowth activity which influences neuronal wiring during development. Eur. J. Neurosci. 25, 168 (2007).

    Google Scholar 

  48. A. Nordin, N.Q.A.V. Sainik, M.S. Zulfarina, I. Naina-Mohamed, A. Saim, and R. Bt Hj Idrus: Honey and epithelial to mesenchymal transition in wound healing: An evidence-based review. Wound Med. 18, 8 (2017).

    Google Scholar 

  49. A. Oryan, E. Alemzadeh, and A. Moshiri: Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis. J. Tissue Viability 25, 98 (2016).

    Google Scholar 

  50. A.C. Daly, F.E. Freeman, T. Gonzalez-Fernandez, S.E. Critchley, J. Nulty, and D.J. Kelly: 3D bioprinting for cartilage and osteochondral tissue engineering. Adv. Healthcare Mater. 6, 1700298 (2017).

    Google Scholar 

  51. K. Nair, M. Gandhi, S. Khalil, K.C. Yan, M. Marcolongo, K. Barbee, and W. Sun: Characterization of cell viability during bioprinting processes. Biotechnol. J. 4, 1168 (2009).

    CAS  Google Scholar 

  52. P. He, J. Zhao, J. Zhang, B. Li, Z. Gou, M. Gou, and X. Li: Bioprinting of skin constructs for wound healing. Burn. Trauma 6, 5 (2018).

    Google Scholar 

  53. A. Barui, P. Banerjee, A. Chaudhary, S. Conjeti, B. Mondal, S. Dey, and J. Chatterjee: Evaluation of angiogenesis in diabetic lower limb wound healing using a natural medicine: A quantitative approach. Wound Med. 6, 26 (2014).

    Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors acknowledge financial support from Department of Science and Technology, Govt. of India vide DST/IFA/12/LSBM/48 to PD and IIEST institute fellowship support to SD.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pallab Datta.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Datta, S., Sarkar, R., Vyas, V. et al. Alginate-honey bioinks with improved cell responses for applications as bioprinted tissue engineered constructs. Journal of Materials Research 33, 2029–2039 (2018). https://doi.org/10.1557/jmr.2018.202

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/jmr.2018.202

Navigation