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Modulating the physico-mechanical properties of polyacrylamide/gelatin hydrogels for tissue engineering application

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Abstract

Along with providing an environment for cell attachment and proliferation, a tissue engineering scaffolds should possess physical and mechanical properties that would fit the target tissue. The present study aimed to manipulate physico-mechanical properties of polyacrylamide/gelatin hydrogels using response surface method-central composite design (RSM-CCD) to reach a scaffold with defined properties. On this demand, mixtures of gelatin and acrylamide (AAm) monomer were used to prepare semi-interpenetrating hydrogels by free radical polymerization of AAm. Selected variables for statistical modeling were chosen to be weight ratios of monomer/crosslinker, monomer/gelatin, and monomer/initiator. The desired responses were compressive modulus, compressive strength, and swelling. Results showed that desired responses could be tailored by varying these parameters with the highest impact for monomer/crosslinker ratio. The swelling ratio of hydrogels was in the range of 947–1654%, while the modulus varied between 5 and 35 kPa. The cyclic compressive test showed the durability of hydrogels under cyclic loadings. Finally, the results of cell attachment and cytocompatibility analyses indicated that the hydrogels were completely biocompatible and enhanced cell attachment. Thus, these hydrogels could potentially be used as tissue engineering scaffolds for load-bearing organs, including muscle and cartilage, or could be used for in vitro differentiation of stem cells using mechanical clues.

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References

  1. Ghasemi-Mobarakeh L, Prabhakaran MP, Morshed M, Nasr-Esfahani M-H, Ramakrishna S (2008) Electrospun poly (ɛ-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials 29(34):4532–4539

    PubMed  CAS  Google Scholar 

  2. Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell stem cell 5(1):17–26

    PubMed  PubMed Central  CAS  Google Scholar 

  3. Amirsadeghi A, Jafari A, Eggermont LJ, Hashemi S-S, Bencherif SA, Khorram M (2020) Vascularization strategies for skin tissue engineering. Biomater Sci 8(15):4073–4094. https://doi.org/10.1039/D0BM00266F

    Article  PubMed  CAS  Google Scholar 

  4. Chan B, Leong K (2008) Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J 17(4):467–479

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Chen F-M, Liu X (2016) Advancing biomaterials of human origin for tissue engineering. Progress Polym Sci 53:86–168

    CAS  Google Scholar 

  6. Mondschein RJ, Kanitkar A, Williams CB, Verbridge SS, Long TE (2017) Polymer structure-property requirements for stereolithographic 3D printing of soft tissue engineering scaffolds. Biomaterials 140:170–188

    PubMed  CAS  Google Scholar 

  7. Eltom A, Zhong G, Muhammad A (2019) Scaffold techniques and designs in tissue engineering functions and purposes: a review. Adv Mater Sci Eng. https://doi.org/10.1155/2019/3429527

    Article  Google Scholar 

  8. O’brien FJ (2011) Biomaterials and scaffolds for tissue engineering. Mater Today 14(3):88–95

    CAS  Google Scholar 

  9. Yang Y, Wang K, Gu X, Leong KW (2017) Biophysical regulation of cell behavior—cross talk between substrate stiffness and nanotopography. Engineering 3(1):36–54

    PubMed  CAS  Google Scholar 

  10. Buxboim A, Rajagopal K, Andre’EX B, Discher DE (2010) How deeply cells feel: methods for thin gels. J Phys Condens Matter 22(19):194116

    PubMed  PubMed Central  Google Scholar 

  11. Kandow CE, Georges PC, Janmey PA, Beningo KA (2007) Polyacrylamide hydrogels for cell mechanics: steps toward optimization and alternative uses. Methods Cell Biol 83:29–46

    PubMed  CAS  Google Scholar 

  12. Fang J, Li P, Lu X, Fang L, Lü X, Ren F (2019) A strong, tough, and osteoconductive hydroxyapatite mineralized polyacrylamide/dextran hydrogel for bone tissue regeneration. Acta biomaterialia 88:503–513

    PubMed  CAS  Google Scholar 

  13. Tse JR, Engler AJ (2010) Preparation of hydrogel substrates with tunable mechanical properties. Curr Protoc Cell Biol 47(1):10–16

    Google Scholar 

  14. Xu J, Sun M, Tan Y, Wang H, Wang H, Li P, Xu Z, Xia Y, Li L, Li Y (2017) Effect of matrix stiffness on the proliferation and differentiation of umbilical cord mesenchymal stem cells. Differentiation 96:30–39

    PubMed  CAS  Google Scholar 

  15. Lee J, Abdeen AA, Zhang D, Kilian KA (2013) Directing stem cell fate on hydrogel substrates by controlling cell geometry, matrix mechanics and adhesion ligand composition. Biomaterials 34(33):8140–8148

    PubMed  CAS  Google Scholar 

  16. Lee JP, Kassianidou E, MacDonald JI, Francis MB, Kumar S (2016) N-terminal specific conjugation of extracellular matrix proteins to 2-pyridinecarboxaldehyde functionalized polyacrylamide hydrogels. Biomaterials 102:268–276

    PubMed  PubMed Central  CAS  Google Scholar 

  17. Pandamooz S, Jafari A, Salehi MS, Jurek B, Ahmadiani A, Safari A, Hassanajili S, Borhani-Haghighi A, Dianatpour M, Niknejad H (2019) Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture. Biotech Bioeng 117(2):305–317

    Google Scholar 

  18. Gribova V, Crouzier T, Picart C (2011) A material’s point of view on recent developments of polymeric biomaterials: control of mechanical and biochemical properties. J Mater Chem 21(38):14354–14366

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Li G, Zhao Y, Zhang L, Gao M, Kong Y, Yang Y (2016) Preparation of graphene oxide/polyacrylamide composite hydrogel and its effect on Schwann cells attachment and proliferation. Colloid Surf B Biointerfaces 143:547–556

    PubMed  CAS  Google Scholar 

  20. Kundu B, Kundu SC (2012) Silk sericin/polyacrylamide in situ forming hydrogels for dermal reconstruction. Biomaterials 33(30):7456–7467

    PubMed  CAS  Google Scholar 

  21. Ranganathan S, Balagangadharan K, Selvamurugan N (2019) Chitosan and gelatin-based electrospun fibers for bone tissue engineering. Int J Biol Macromol 133:354–364

    PubMed  CAS  Google Scholar 

  22. Nafea EH, Poole-Warren LA, Martens PJ (2015) Bioactivity of permselective PVA hydrogels with mixed ECM analogues. J Biomed Mater Res Part A 103(12):3727–3735

    CAS  Google Scholar 

  23. Jafari A, Amirsadeghi A, Hassanajili S, Azarpira N (2020) Bioactive antibacterial bilayer PCL/gelatin nanofibrous scaffold promotes full-thickness wound healing. Int J Pharm 583:119413

    PubMed  CAS  Google Scholar 

  24. Discher DE, Janmey P, Wang Y-l (2005) Tissue cells feel and respond to the stiffness of their substrate. Science 310(5751):1139–1143

    PubMed  CAS  Google Scholar 

  25. Madl CM, Heilshorn SC, Blau HM (2018) Bioengineering strategies to accelerate stem cell therapeutics. Nature 557(7705):335

    PubMed  PubMed Central  CAS  Google Scholar 

  26. Langhans SA (2018) Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front Pharm 9:6

    Google Scholar 

  27. Hamri S, Lerari D, Sehailia M, Dali-Youcef B, Bouchaour T, Bachari K (2018) Prediction of equilibrium swelling ratio on synthesized polyacrylamide hydrogel using central composite design modeling. Int J Plast Technol 22(2):247–261

    CAS  Google Scholar 

  28. Sabbagh F, Muhamad II, Nazari Z, Mobini P, Taraghdari SB (2018) From formulation of acrylamide-based hydrogels to their optimization for drug release using response surface methodology. Mater Sci Eng C 92:20–25

    CAS  Google Scholar 

  29. Mehrali M, Thakur A, Kadumudi FB, Pierchala MK, Cordova JAV, Shahbazi M-A, Mehrali M, Pennisi CP, Orive G, Gaharwar AK (2019) Pectin methacrylate (PEMA) and gelatin-based hydrogels for cell delivery: converting waste materials into biomaterials. ACS Appl Mater Interfaces 11(13):12283–12297

    PubMed  CAS  Google Scholar 

  30. Qin Q, Tang Q, Li Q, He B, Chen H, Wang X, Yang P (2014) Incorporation of H3PO4 into three-dimensional polyacrylamide-graft-starch hydrogel frameworks for robust high-temperature proton exchange membrane fuel cells. Int J Hydrog Energy 39(9):4447–4458

    CAS  Google Scholar 

  31. Mandal BB, Kapoor S, Kundu SC (2009) Silk fibroin/polyacrylamide semi-interpenetrating network hydrogels for controlled drug release. Biomaterials 30(14):2826–2836

    PubMed  CAS  Google Scholar 

  32. Zhang L, Liu J, Zheng X, Zhang A, Zhang X, Tang K (2019) Pullulan dialdehyde crosslinked gelatin hydrogels with high strength for biomedical applications. Carbohydrate Polym 216:45–53

    CAS  Google Scholar 

  33. Sobhanian P, Khorram M, Hashemi S-S, Mohammadi A (2019) Development of nanofibrous collagen-grafted poly (vinyl alcohol)/gelatin/alginate scaffolds as potential skin substitute. Int J Biol Macromol 130:977–987

    PubMed  CAS  Google Scholar 

  34. Carvalho IC, Mansur HS (2017) Engineered 3D-scaffolds of photocrosslinked chitosan-gelatin hydrogel hybrids for chronic wound dressings and regeneration. Mater Sci Eng C 78:690–705

    CAS  Google Scholar 

  35. Samanta HS, Ray SK (2014) Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide. Carbohydr Polym 99:666–678

    PubMed  CAS  Google Scholar 

  36. Cong HP, Wang P, Yu SH (2014) Highly elastic and superstretchable graphene oxide/polyacrylamide hydrogels. Small 10(3):448–453

    PubMed  CAS  Google Scholar 

  37. Yan X, Yang J, Chen F, Zhu L, Tang Z, Qin G, Chen Q, Chen G (2018) Mechanical properties of gelatin/polyacrylamide/graphene oxide nanocomposite double-network hydrogels. Comp Sci Tech 163:81–88

    CAS  Google Scholar 

  38. Ghobashy MM, El-Damhougy BK, Nady N, Abd El-Wahab H, Naser A, Abdelhai F (2018) Radiation crosslinking of modifying super absorbent (polyacrylamide/gelatin) hydrogel as fertilizers carrier and soil conditioner. J Polym Environ 26(9):3981–3994

    CAS  Google Scholar 

  39. Loh QL, Choong C (2013) Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng Part B Rev 19(6):485–502

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Park J, Kim D (2010) Effect of polymer solution concentration on the swelling and mechanical properties of glycol chitosan superporous hydrogels. J Appl Polym Sci 115(6):3434–3441

    CAS  Google Scholar 

  41. Jaiswal M, Dinda AK, Gupta A, Koul V (2010) Polycaprolactone diacrylate crosslinked biodegradable semi-interpenetrating networks of polyacrylamide and gelatin for controlled drug delivery. Biomed Mater 5(6):065014

    PubMed  Google Scholar 

  42. Zhang Y, Chen H, Li Y, Fang A, Wu T, Shen C, Zhao Y, Zhang G (2020) A transparent sericin-polyacrylamide interpenetrating network hydrogel as visualized dressing material. Polym Test 87:106517

    CAS  Google Scholar 

  43. Poursamar SA, Lehner AN, Azami M, Ebrahimi-Barough S, Samadikuchaksaraei A, Antunes APM (2016) The effects of crosslinkers on physical, mechanical, and cytotoxic properties of gelatin sponge prepared via in-situ gas foaming method as a tissue engineering scaffold. Mater Sci Eng C 63:1–9

    CAS  Google Scholar 

  44. Huang J, Zhao L, Wang T, Sun W, Tong Z (2016) Nir-triggered rapid shape memory PAM–GO–gelatin hydrogels with high mechanical strength. ACS Appl Mater Interfaces 8(19):12384–12392

    PubMed  CAS  Google Scholar 

  45. Hu X, Feng L, Xie A, Wei W, Wang S, Zhang J, Dong W (2014) Synthesis and characterization of a novel hydrogel: salecan/polyacrylamide semi-IPN hydrogel with a desirable pore structure. J Mater Chem B 2(23):3646–3658

    PubMed  CAS  Google Scholar 

  46. Meng Z, Thakur T, Chitrakar C, Jaiswal MK, Gaharwar AK, Yakovlev VV (2017) Assessment of local heterogeneity in mechanical properties of nanostructured hydrogel networks. Acs Nano 11(8):7690–7696

    PubMed  CAS  Google Scholar 

  47. Wang Q, Hou R, Cheng Y, Fu J (2012) Super-tough double-network hydrogels reinforced by covalently compositing with silica-nanoparticles. Soft Matter 8(22):6048–6056

    CAS  Google Scholar 

  48. Chanda M (2013) Introduction to polymer science and chemistry: a problem-solving approach. CRC Press, Florida

    Google Scholar 

  49. Maitra J, Shukla VK (2014) Cross-linking in hydrogels-a review. Am J Polym Sci 4(2):25–31

    Google Scholar 

  50. Ou K, Dong X, Qin C, Ji X, He J (2017) Properties and toughening mechanisms of PVA/PAM double-network hydrogels prepared by freeze-thawing and anneal-swelling. Mater Sci Eng C 77:1017–1026

    CAS  Google Scholar 

  51. Wang B, Xiao X, Zhang Y, Liao L (2019) High strength dual-crosslinked hydrogels with photo-switchable color changing behavior. Eur Polym J 116:545–553. https://doi.org/10.1016/j.eurpolymj.2019.04.035

    Article  CAS  Google Scholar 

  52. Mohan YM, Murthy PK, Raju KM (2005) Synthesis, characterization and effect of reaction parameters on swelling properties of acrylamide–sodium methacrylate superabsorbent copolymers. React Funct Polym 63(1):11–26

    CAS  Google Scholar 

  53. Bajpai A, Giri A (2003) Water sorption behaviour of highly swelling (carboxy methylcellulose-g-polyacrylamide) hydrogels and release of potassium nitrate as agrochemical. Carbohydr Polym 53(3):271–279

    CAS  Google Scholar 

  54. Merlin DL, Sivasankar B (2009) Synthesis and characterization of semi-interpenetrating polymer networks using biocompatible polyurethane and acrylamide monomer. Eur Polym J 45(1):165–170

    CAS  Google Scholar 

  55. Li X, Wu W, Wang J, Duan Y (2006) The swelling behavior and network parameters of guar gum/poly (acrylic acid) semi-interpenetrating polymer network hydrogels. Carbohydr Polym 66(4):473–479

    CAS  Google Scholar 

  56. Singhal R, Tomar RS, Nagpal A (2009) Effect of cross-linker and initiator concentration on the swelling behaviour and network parameters of superabsorbent hydrogels based on acrylamide and acrylic acid. Int J Plast Technol 13(1):22

    CAS  Google Scholar 

  57. Zhou C, Wu Q, Zhang Q (2011) Dynamic rheology studies of in situ polymerization process of polyacrylamide–cellulose nanocrystal composite hydrogels. Colloid Polym Sci 289(3):247–255

    CAS  Google Scholar 

  58. Lahooti B, Khorram M, Karimi G, Mohammadi A, Emami A (2016) Modeling and optimization of antibacterial activity of the chitosan-based hydrogel films using central composite design. J Biomed Mater Res Part A 104(10):2544–2553

    CAS  Google Scholar 

  59. Sun G, Zhang X, Bao Z, Lang X, Zhou Z, Li Y, Feng C, Chen X (2018) Reinforcement of thermoplastic chitosan hydrogel using chitin whiskers optimized with response surface methodology. Carbohydr Polym 189:280–288

    PubMed  CAS  Google Scholar 

  60. Zhao L, Li Q, Xu X, Kong W, Li X, Su Y, Yue Q, Gao B (2016) A novel Enteromorpha based hydrogel optimized with Box-Behnken response surface method: synthesis, characterization and swelling behaviors. Chem Eng J 287:537–544

    CAS  Google Scholar 

  61. Kumru B, Molinari V, Shalom M, Antonietti M, Schmidt BV (2018) Tough high modulus hydrogels derived from carbon-nitride via an ethylene glycol co-solvent route. Soft Matter 14(14):2655–2664

    PubMed  CAS  Google Scholar 

  62. Liu X, Duan L, Gao G (2017) Rapidly self-recoverable and fatigue-resistant hydrogels toughened by chemical crosslinking and hydrophobic association. Eur Polym J 89:185–194

    CAS  Google Scholar 

  63. Li J, Liu H, Wang C, Huang G (2017) A facile method to fabricate hybrid hydrogels with mechanical toughness using a novel multifunctional cross-linker. RSC Adv 7(56):35311–35319

    CAS  Google Scholar 

  64. Caliari SR, Burdick JA (2016) A practical guide to hydrogels for cell culture. Nature Methods 13(5):405

    PubMed  PubMed Central  CAS  Google Scholar 

  65. Davidenko N, Schuster CF, Bax DV, Farndale RW, Hamaia S, Best SM, Cameron RE (2016) Evaluation of cell binding to collagen and gelatin: a study of the effect of 2D and 3D architecture and surface chemistry. J Mater Sci Mater Med 27(10):148

    PubMed  PubMed Central  Google Scholar 

  66. Hu X, Wang Y, Zhang L, Xu M (2017) Morphological and mechanical properties of tannic acid/PAAm semi-IPN hydrogels for cell adhesion. Polym Test 61:314–323

    CAS  Google Scholar 

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Jafari, A., Hassanajili, S., Ghaffari, F. et al. Modulating the physico-mechanical properties of polyacrylamide/gelatin hydrogels for tissue engineering application. Polym. Bull. 79, 1821–1842 (2022). https://doi.org/10.1007/s00289-021-03592-2

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