10.1007/s40204-015-0041-3

PEG-penetrated chitosan–alginate co-polysaccharide-based partially and fully cross-linked hydrogels as ECM mimic for tissue engineering applications

  1. Department of Biochemistry, University of Kerala, Karyavattom, Thiruvananthapuram, Kerala, IN
Cover Image

Published in Issue 2015-09-15

How to Cite

Radhakrishnan, A., Jose, G. M., & Kurup, M. (2015). PEG-penetrated chitosan–alginate co-polysaccharide-based partially and fully cross-linked hydrogels as ECM mimic for tissue engineering applications. Progress in Biomaterials, 4(2-4 (December 2015). https://doi.org/10.1007/s40204-015-0041-3

Abstract

Abstract The emerging strategy of tissue engineering for the management of end-stage organ failure and associated complications mainly relies on ECM mimicking scaffolds for neo-tissue genesis. In the current study, novel polyethylene glycol interpenetrated cross-linked hydrogel scaffold based on a co-polysaccharide (PIAC) synthesized from two marine heteropolysaccharides, alginate and chitosan, was designed. Partially cross-linked (PIAC-P) and fully cross-linked hydrogels (PIAC-F) were prepared. The physiochemical evaluations of both the hydrogels revealed the presence of alginate fraction and extensive –OH groups on the surface, sufficient water content and water holding capacity. The porosity and bulk density were also appreciable. The scaffolds were hemocompatible and were able to adsorb appreciable plasma proteins on to the surface. MTT assay on hydrogel extracts and direct contact assay showed the nontoxic effects of fibroblast cells upon contact with the hydrogel. Live/dead assay using ethidium bromide/acridine orange cocktail on fibroblast cells grown on the hydrogels after 5 days of initial seeding displayed green nucleus revealing the non-apoptotic cells. PIAC-P hydrogels were superior to certain aspects due to the availability of free functional groups than PIAC-F where most of these groups were utilized for cross-linking. The biological evaluations confirmed the healthy being and 3D growth of fibroblasts on the porous networks of both the hydrogels. The present hydrogel can form an ECM mimic and can form a potent candidate for various tissue engineering applications.

Keywords

  • Tissue engineering,
  • Cross-linked hydrogels,
  • Alginate,
  • Chitosan,
  • ECM mimic

References

  1. Baskurt and Meiselman (1997) Cellular determinants of low-shear blood viscosity (pp. 235-247) https://doi.org/10.1016/S0006-355X(97)00027-9
  2. Burdick and Vunjak-Novakovic (2009) Engineered microenvironments for controlled stem cell differentiation (pp. 205-219) https://doi.org/10.1089/ten.tea.2008.0131
  3. Camci-Unal et al. (2014) Hydrogels for cardiac tissue engineering https://doi.org/10.1038/am.2014.19
  4. Cattell et al. (1996) Age-related changes in amounts and concentrations of collagen and elastin in normotensive human thoracic aorta (pp. 73-84) https://doi.org/10.1016/0009-8981(95)06174-6
  5. Cox and Erler (2011) Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer (pp. 165-178) https://doi.org/10.1242/dmm.004077
  6. Daniele et al. (2014) Interpenetrating networks based on gelatin methacrylamide and PEG formed using concurrent thiol click chemistries for hydrogel tissue engineering scaffolds (pp. 1845-1856) https://doi.org/10.1016/j.biomaterials.2013.11.009
  7. Dawlee et al. (2005) Oxidized chondroitin sulfate-cross-linked gelatin matrixes: a new class of hydrogels (pp. 2040-2048) https://doi.org/10.1021/bm050013a
  8. Dragan (2014) Design and applications of interpenetrating polymer network hydrogels. A review (pp. 572-590) https://doi.org/10.1016/j.cej.2014.01.065
  9. Drury and Mooney (2003) Hydrogels for tissue engineering: scaffold design variables and applications (pp. 4337-4351) https://doi.org/10.1016/S0142-9612(03)00340-5
  10. Even-Ram et al. (2006) Matrix control of stem cell fate (pp. 645-647) https://doi.org/10.1016/j.cell.2006.08.008
  11. Finosh and Jayabalan (2012) Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure (pp. 1-14) https://doi.org/10.4161/biom.19429
  12. Finosh and Jayabalan (2015) Hybrid amphiphilic bimodal hydrogels having mechanical and biological recognition characteristics for cardiac tissue engineering (pp. 38183-38201) https://doi.org/10.1039/C5RA04448K
  13. Finosh et al. (2015) Hybrid alginate-polyester bimodal network hydrogel for tissue engineering—Influence of structured water on long-term cellular growth https://doi.org/10.1016/j.colsurfb.2015.03.020
  14. Freudenberg et al. (2009) A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases (pp. 5049-5060) https://doi.org/10.1016/j.biomaterials.2009.06.002
  15. Gemeinhart et al. (2000) pH-sensitivity of fast responsive superporous hydrogels (pp. 1371-1380) https://doi.org/10.1163/156856200744390
  16. Gnanaprakasam Thankam and Muthu (2013) Influence of plasma protein–hydrogel interaction moderated by absorption of water on long-term cell viability in amphiphilic biosynthetic hydrogels https://doi.org/10.1039/c3ra43710h
  17. Gnanaprakasam Thankam and Muthu (2014) Alginate based hybrid copolymer hydrogels—Influence of pore morphology on cell–material interaction (pp. 235-244) https://doi.org/10.1016/j.carbpol.2014.05.083
  18. Gnanaprakasam Thankam et al. (2013) Growth and survival of cells in biosynthetic poly vinyl alcohol–alginate IPN hydrogels for cardiac applications (pp. 137-145) https://doi.org/10.1016/j.colsurfb.2013.01.069
  19. Gong et al. (2003) Double-network hydrogels with extremely high mechanical strength (pp. 1155-1158) https://doi.org/10.1002/adma.200304907
  20. Hofmann et al. (2005) Monitoring of bone marrow cell homing into the infarcted human myocardium (pp. 2198-2202) https://doi.org/10.1161/01.CIR.0000163546.27639.AA
  21. Ishaug et al. (1997) Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds (pp. 17-28) https://doi.org/10.1002/(SICI)1097-4636(199707)36:1<17::AID-JBM3>3.0.CO;2-O
  22. Jiang et al. (2013) Fibrin-loaded porous poly(ethylene glycol) hydrogels as scaffold materials for vascularized tissue formation (pp. 224-234) https://doi.org/10.1089/ten.tea.2012.0120
  23. Khoda et al. (2013) Spatially multi-functional porous tissue scaffold (pp. 174-182) https://doi.org/10.1016/j.proeng.2013.05.108
  24. Levengood and Zhang (2014) Chitosan-based scaffolds for bone tissue engineering (pp. 3161-3184) https://doi.org/10.1039/c4tb00027g
  25. Liu and Ma (2004) Polymeric scaffolds for bone tissue engineering (pp. 477-486) https://doi.org/10.1023/B:ABME.0000017544.36001.8e
  26. Lohani et al. (2014) Interpenetrating polymer networks as innovative drug delivery systems https://doi.org/10.1155/2014/583612
  27. Madden et al. (2010) Proangiogenic scaffolds as functional templates for cardiac tissue engineering https://doi.org/10.1073/pnas.1006442107
  28. Mikos et al. (1994) Wetting of poly(L-lactic acid) and poly(DL-lactic-co-glycolic acid) foams for tissue culture (pp. 55-58) https://doi.org/10.1016/0142-9612(94)90197-X
  29. Myung et al. (2008) Progress in the development of interpenetrating polymer network hydrogels (pp. 647-657) https://doi.org/10.1002/pat.1134
  30. Nanda et al. (2013) Preparation and characterization of poly(vinyl alcohol)-chondroitin sulphate hydrogel as scaffolds for articular cartilage regeneration https://doi.org/10.1155/2013/516021
  31. Peppas et al. (2000) Physicochemical foundations and structural design of hydrogels in medicine and biology (pp. 9-29) https://doi.org/10.1146/annurev.bioeng.2.1.9
  32. Peppas et al. (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology (pp. 1345-1360) https://doi.org/10.1002/adma.200501612
  33. Pramanik et al. (2015) In vitro study of surface modified poly(ethylene glycol)-impregnated sintered bovine bone scaffolds on human fibroblast cells https://doi.org/10.1038/srep09806
  34. Qu et al. (2006) In vitro study on hemocompatibility and cytocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (pp. 1107-1121) https://doi.org/10.1163/156856206778530704
  35. Stosich and Mao (2007) Adipose tissue engineering from human adult stem cells: clinical implications in plastic and reconstructive surgery (pp. 71-83) https://doi.org/10.1097/01.prs.0000244840.80661.e7
  36. Strehin et al. (2010) A versatile pH sensitive chondroitin sulfate-PEG tissue adhesive and hydrogel (pp. 2788-2797) https://doi.org/10.1016/j.biomaterials.2009.12.033
  37. Thankam and Muthu (2014) Infiltration and sustenance of viability of cells by amphiphilic biosynthetic biodegradable hydrogels https://doi.org/10.1007/s10856-014-5234-0
  38. Thankam and Muthu (2014) Influence of physical and mechanical properties of amphiphilic biosynthetic hydrogels on long-term cell viability (pp. 111-122) https://doi.org/10.1016/j.jmbbm.2014.03.010
  39. Thankam and Muthu (2014) Alginate based hybrid copolymer hydrogels—Influence of pore morphology on cell–material interaction https://doi.org/10.1016/j.carbpol.2014.05.083
  40. Thomson et al. (1995) Biodegradable polymer scaffolds to regenerate organs (pp. 245-274) Springer https://doi.org/10.1007/3540587888_18
  41. Watt and Hogan (2000) Out of Eden: stem cells and their niches (pp. 1427-1430) https://doi.org/10.1126/science.287.5457.1427
  42. Wu et al. (2007) Preparation and assessment of glutaraldehyde-crosslinked collagen–chitosan hydrogels for adipose tissue engineering (pp. 59-65) https://doi.org/10.1002/jbm.a.31003
  43. Yu et al. (2013) An injectable hyaluronic acid/PEG hydrogel for cartilage tissue engineering formed by integrating enzymatic crosslinking and Diels–Alder “click chemistry” (pp. 1082-1090) https://doi.org/10.1039/C3PY00869J