Skip to main content

3D Printing Methyl Cellulose Hydrogel Wound Dressings with Parameter Exploration Via Computational Fluid Dynamics Simulation



To investigate and optimize the use of methyl cellulose in the fabrication of three-dimensional (3D) printed drug-loaded hydrogel wound dressings for the treatment of burns.


The effects of incorporating various salts on the properties of methyl cellulose, especially the gelation temperature was investigated for methyl cellulose to undergo gelation at skin temperature (i.e., 31.7°C). The optimized methyl cellulose and salt compositions were then loaded with various drugs beneficial for the treatment of burns. Printability and cumulative release profiles for selected drugs were then obtained, which were then fitted to common release kinetic models. Computational Fluid Dynamics (CFD) simulation was also explored to investigate the relationship between printing parameters and the hydrogel filament produced during extrusion.


The printed hydrogels had moderate dimensional integrity, were found to be stable for up to 2 weeks and demonstrated good swelling properties. In vitro drug release studies of various drugs showed that the hydrogel was able to release various drugs within 6 h and release profiles were fitted to common in vitro drug release models, such as the Korsmeyer Peppas model and the Weibull model. While there were deviations from the actual printing process, CFD simulation was able to predict the shape of the printed structure and showed fair accuracy in determining the mass flow rate and line width of extruded hydrogels.


Methyl cellulose hydrogels with optimized salt composition demonstrated suitable properties for a wound dressing application, revealing its potential to be used for in situ wound dressing applications.

This is a preview of subscription content, access via your institution.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8







Computational Fluid Dynamics

DI water:

Deionized water


Field Emission Scanning Electron Microscopy


Fourier Transform Infrared




Lidocaine hydrochloride


Methyl cellulose


Phosphate Buffered Saline


Potassium sulfate


Sodium citrate


Sodium sulfate


Silver sulfadiazine




Volume of Fluid


  1. Kaddoura I, Abu-Sittah G, Ibrahim A, Karamanoukian R, Papazian N. Burn injury: review of pathophysiology and therapeutic modalities in major burns. Ann Burns Fire Disasters. 2017;30(2):95–102.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Gear AJ, Hellewell TB, Wright HR, Mazzarese PM, Arnold PB, Rodeheaver GT, Edlich RF. A new silver sulfadiazine water soluble gel. Burns. 1997;23(5):387–91.

    CAS  Article  Google Scholar 

  3. Erring M, Gaba S, Mohsina S, Tripathy S, Sharma RK. Comparison of efficacy of silver-nanoparticle gel, nano-silver-foam and collagen dressings in treatment of partial thickness burn wounds. Burns. 2019;45(8):1888–94.

    Article  Google Scholar 

  4. Stoica AE, Chircov C, Grumezescu AM. Hydrogel dressings for the treatment of burn wounds: an up-to-date overview. Materials (Basel). 2020;13:12.

    Article  Google Scholar 

  5. Constante G, Apsite I, Alkhamis H, Dulle M, Schwarzer M, Caspari A, Synytska A, Salehi S, Ionov L. 4D biofabrication using a combination of 3D printing and melt-Electrowriting of shape-morphing polymers. ACS Appl Mater Interfaces. 2021;13(11):12767–76.

    CAS  Article  Google Scholar 

  6. Opasanon S, Muangman P, Namviriyachote N. Clinical effectivenessof alginate silver dressingin outpatient managementof partial-thickness burns. Int Wound J. 2010;7:467–71.

    Article  Google Scholar 

  7. Stubbe B, Mignon A, Declercq H, Vlierberghe S, Dubruel P. Development of gelatin-alginate hydrogels for burn wound treatment. Macromol Biosci. 2019;19(8).

  8. Zheng Y, Yuan W, Liu H, Huang S, Bian L, Guo R. Injectable supramolecular gelatin hydrogel loading of resveratrol and histatin-1 for burn wound therapy. Biomater Sci. 2020;8(17):4810–20.

    Article  Google Scholar 

  9. Kumar PTS, Praveen G, Raj M, Chennazhi KP, Jayakumar R. Flexible, micro-porous chitosan–gelatin hydrogel/nanofibrin composite bandages for treating burn wounds. RSC Adv. 2014;4(110):65081–7.

    CAS  Article  Google Scholar 

  10. Wang T, Zhu X-K, Xue X-T, Wu D-Y. Hydrogel sheets of chitosan, honey and gelatin as burn wound dressings. Carbohydr Polym. 2012;88(1):75–83.

    CAS  Article  Google Scholar 

  11. Baxter RM, Dai T, Kimball J, Wang E, Hamblin MR, Wiesmann WP, McCarthy SJ, Baker SM. Chitosan dressing promotes healing in third degree burns in mice: gene expression analysis shows biphasic effects for rapid tissue regeneration and decreased fibrotic signaling. J Biomed Mater Res A. 2013;101(2):340–8.

    Article  Google Scholar 

  12. Dai T, Tanaka M, Huang YY, Hamblin MR. Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert Rev Anti-Infect Ther. 2011;9(7):857–79.

    CAS  Article  Google Scholar 

  13. Kim MH, Park H, Nam HC, Park SR, Jung JY, Park WH. Injectable methylcellulose hydrogel containing silver oxide nanoparticles for burn wound healing. Carbohydr Polym. 2018;181:579–86.

    CAS  Article  Google Scholar 

  14. Pakulska MM, Vulic K, Tam RY, Shoichet MS. Hybrid Crosslinked methylcellulose hydrogel: a predictable and tunable platform for local drug delivery. Adv Mater. 2015;27(34):5002–8.

    CAS  Article  Google Scholar 

  15. Baumann MD, Kang CE, Stanwick JC, Wang Y, Kim H, Lapitsky Y, Shoichet MS. An injectable drug delivery platform for sustained combination therapy. J Control Release. 2009;138(3):205–13.

    CAS  Article  Google Scholar 

  16. Pakulska MM, Vulic K, Shoichet MS. Affinity-based release of chondroitinase ABC from a modified methylcellulose hydrogel. J Control Release. 2013;171(1):11–6.

    CAS  Article  Google Scholar 

  17. Zhang Y, Gao C, Li X, Xu C, Zhang Y, Sun Z, Liu Y, Gao J. Thermosensitive methyl cellulose-based injectable hydrogels for post-operation anti-adhesion. Carbohydr Polym. 2014;101:171–8.

    CAS  Article  Google Scholar 

  18. Contessi N, Altomare L, Filipponi A, Farè S. Thermo-responsive properties of methylcellulose hydrogels for cell sheet engineering. Mater Lett. 2017;207:157–60.

    CAS  Article  Google Scholar 

  19. Baumann MD, Kang CE, Tator CH, Shoichet MS. Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury. Biomaterials. 2010;31(30):7631–9.

    CAS  Article  Google Scholar 

  20. Xu Y, Wang C, Tam KC, Li L. Salt-assisted and salt-suppressed sol-gel transitions of methylcellulose in water. Langmuir. 2004;20(3):646–52.

    Article  Google Scholar 

  21. Altomare L, Cochis A, Carletta A, Rimondini L, Fare S. Thermo-responsive methylcellulose hydrogels as temporary substrate for cell sheet biofabrication. J Mater Sci Mater Med. 2016;27(5):95.

    Article  Google Scholar 

  22. Cochis A, Bonetti L, Sorrentino R, Contessi Negrini N, Grassi F, Leigheb M, Rimondini L, Fare S. 3D printing of thermo-responsive methylcellulose hydrogels for cell-sheet engineering. Materials (Basel). 2018;11(4).

  23. Contessi Negrini N, Bonetti L, Contili L, Farè S. 3D printing of methylcellulose-based hydrogels. Bioprinting. 2018;10:e00024.

    Article  Google Scholar 

  24. Highley CB, Rodell CB, Burdick JA. Direct 3D printing of shear-thinning hydrogels into self-healing hydrogels. Adv Mater. 2015;27(34):5075–9.

    CAS  Article  Google Scholar 

  25. Chen Z, Zhao D, Liu B, Nian G, Li X, Yin J, Qu S, Yang W. 3D printing of multifunctional hydrogels. Adv Funct Mater. 2019;29(20).

  26. Wei J, Wang J, Su S, Wang S, Qiu J, Zhang Z, Christopher G, Ning F, Cong W. 3D printing of an extremely tough hydrogel. RSC Adv. 2015;5(99):81324–9.

    CAS  Article  Google Scholar 

  27. Lepowsky E, Muradoglu M, Tasoglu S. Towards preserving post-printing cell viability and improving the resolution: past, present, and future of 3D bioprinting theory. Bioprinting. 2018;11.

  28. Mirani B, Stefanek E, Godau B, Hossein Dabiri SM, Akbari M. Microfluidic 3D printing of a photo-cross-linkable bioink using insights from computational modeling. ACS Biomater Sci Eng. 2021;7(7):3269–80.

    CAS  Article  Google Scholar 

  29. Gohl J, Markstedt K, Mark A, Hakansson K, Gatenholm P, Edelvik F. Simulations of 3D bioprinting: predicting bioprintability of nanofibrillar inks. Biofabrication. 2018;10(3):034105.

    Article  Google Scholar 

  30. Kantaros A, Chatzidai N, Karalekas D. 3D printing-assisted design of scaffold structures. Int J Adv Manuf Technol. 2015;82(1-4):559–71.

    Article  Google Scholar 

  31. Reina-Romo E, Mandal S, Amorim P, Bloemen V, Ferraris E, Geris L. Towards the experimentally-informed in Silico nozzle design optimization for extrusion-based bioprinting of shear-thinning hydrogels. Front Bioeng Biotechnol. 2021;9:701778.

    Article  Google Scholar 

  32. Gosset A, Barreiro-Villaverde D, Becerra Permuy JC, Lema M, Ares-Pernas A, Abad Lopez MJ. Experimental and numerical investigation of the extrusion and deposition process of a poly(lactic acid) Strand with fused deposition modeling. Polymers (Basel). 2020;12(12).

  33. Leppiniemi J, Lahtinen P, Paajanen A, Mahlberg R, Metsa-Kortelainen S, Pinomaa T, Pajari H, Vikholm-Lundin I, Pursula P, Hytonen VP. 3D-printable bioactivated Nanocellulose-alginate hydrogels. ACS Appl Mater Interfaces. 2017;9(26):21959–70.

    CAS  Article  Google Scholar 

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

    Article  Google Scholar 

  35. 5 - Mathematical models of drug release. In: Bruschi ML, editor. Strategies to Modify the Drug Release from Pharmaceutical Systems: Woodhead Publishing; 2015. p. 63-86.

  36. Greenshields CJ. OpenFOAM User Guide Version 9. In.: The OpenFOAM Foundation 2021.

  37. Mohsin H, Sultan U, Joya YF, Ahmed S, Awan MS, Arshad SN. Development and characterization of cobalt based nano-structured super hydrophobic coating. In: Science I, editor.14th International Symposium on Advanced Materials: IOP Publishing; 2016. p. 012038.

  38. Bain MK, Bhowmick B, Maity D, Mondal D, Mollick MM, Rana D, Chattopadhyay D. Synergistic effect of salt mixture on the gelation temperature and morphology of methylcellulose hydrogel. Int J Biol Macromol. 2012;51(5):831–6.

    CAS  Article  Google Scholar 

  39. Price MJ, Trbovich M. Chapter 50 - thermoregulation following spinal cord injury. In: Romanovsky AA, editor. Handbook of Clinical Neurology: Elsevier; 2018. p. 799-820.

  40. Sarkar N. Kinetics of thermal gelation of methylcellulose and hydroxypropylmethylcellulose in aqueous solutions. Carbohydr Polym. 1995;26(3):195–203.

    CAS  Article  Google Scholar 

  41. Almeida N, Rakesh L, Zhao J. The effect of kappa carrageenan and salt on thermoreversible gelation of methylcellulose. Polym Bull. 2018;75(9):4227–43.

    CAS  Article  Google Scholar 

  42. Law N, Doney B, Glover H, Qin Y, Aman ZM, Sercombe TB, Liew LJ, Dilley RJ, Doyle BJ. Characterisation of hyaluronic acid methylcellulose hydrogels for 3D bioprinting. J Mech Behav Biomed Mater. 2018;77:389–99.

    CAS  Article  Google Scholar 

  43. Fozzard HA, Sheets MF, Hanck DA. The sodium channel as a target for local anesthetic drugs. Front Pharmacol. 2011;2:68.

    CAS  Article  Google Scholar 

  44. Long J, Etxeberria AE, Nand AV, Bunt CR, Ray S, Seyfoddin A. A 3D printed chitosan-pectin hydrogel wound dressing for lidocaine hydrochloride delivery. Mater Sci Eng C Mater Biol Appl. 2019;104:109873.

    CAS  Article  Google Scholar 

  45. Han Z, Lu L, Wang L, Yan Z, Wang X. Development and validation of an HPLC method for simultaneous determination of ibuprofen and 17 related compounds. Chromatographia. 2017;80(9):1353–60.

    CAS  Article  Google Scholar 

  46. Giang DT, Hoang VD. Comparative study of RP-HPLC and UV spectrophotometric techniques for the simultaneous determination of amoxicillin and Cloxacillin in capsules. J Young Pharm. 2010;2(2):190–5.

    CAS  Article  Google Scholar 

  47. Mathematical models of drug release. In. Strategies to Modify the Drug Release from Pharmaceutical Systems; 2015. p. 63-86.

  48. Papadopoulou V, Kosmidis K, Vlachou M, Macheras P. On the use of the Weibull function for the discernment of drug release mechanisms. Int J Pharm. 2006;309(1-2):44–50.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Chi-Hwa Wang.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information


(DOCX 3748 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Teoh, J.H., Abdul Shakoor, F.T. & Wang, CH. 3D Printing Methyl Cellulose Hydrogel Wound Dressings with Parameter Exploration Via Computational Fluid Dynamics Simulation. Pharm Res 39, 281–294 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • 3D printing
  • burns
  • drug delivery
  • computational fluid dynamics
  • wound dtressing