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Gelatin-Based Hydrogels for Controlled Cell Assembly

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Biomedical Applications of Hydrogels Handbook

Abstract

Controlled cell assembly technique is a new research area in complex organ development technologies. Gelatin-based hydrogels, such as gelatin, gelatin/alginate, gelatin/chitosan, gelatin/fibrinogen, gelatin/hyaluronan, and gelatin/alginate/fibrinogen, have played an important role in the rapid fabrication of tissue or organs with well-defined structures and functions. Cryoprotectants, such as dimethylsulfoxide (DMSO) and glycerol, can be easily incorporated into the system for long-term conservation of the cell containing constructs. Hepatocytes, chondrocytes, cardiac myocytes, and adipose-derived stromal cells (ADSCs) are used to show function of the assembled cells. ADSCs can be controlled to differentiate into different targeted cell types according to their positions within the orderly predesigned three-dimensional (3D) constructs. A multicellular model for the metabolic syndrome was established along with the development of the double-syringe deposition system which lead to a hybrid cell/hydrogels construct with a vascular-like network fabricated using a digital model. The preliminary results indicate that the double-syringe assembly technique is a powerful tool for fabricating complex constructs with special intrinsic/extrinsic structures, and has the potential to be widely used in regenerative medicine and drug screening.

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References

  1. Keeffe EB (2001) Liver transplantation: current status and novel approaches to liver replacement. Gastroenterology 120(3):749–762

    Article  CAS  Google Scholar 

  2. Yan YN, Wang XH, Xiong Z, Liu HX, Liu F, Lin F, Wu RD, Zhang RJ, Lu QP (2005) Direct construction of a three-dimensional structure with cells and hydrogel. J Bioact Compat Polym 20(3):259–269

    Article  CAS  Google Scholar 

  3. Yan YN, Wang XH, Pan YQ, Liu HX, Cheng J, Xiong Z, Lin F, Wu RD, Zhang J, Lu QP (2005) Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique. Biomaterials 26:5864–5871

    Article  CAS  Google Scholar 

  4. Wang XH, Yan YN, Pan YQ, Xiong Z, Liu HX, Cheng J, Liu F, Lin F, Wu RD, Zhang RJ, Lu QP (2006) Generation of three-dimensional hepatocyte/gelatin structures with rapid prototyping system. Tissue Eng 12:83–90

    Article  CAS  Google Scholar 

  5. Xu W, Wang XH, Yan YN, Zheng W, Xiong Z, Lin F, Wu RD, Zhang RJ (2007) Rapid prototyping three-dimensional cell/gelatin/fibrinogen constructs for medical regeneration. J Bioact Compat Polym 22(4):363–377

    Article  CAS  Google Scholar 

  6. Yao R, Zhang RJ, Wang XH (2009) Design and evaluation of a cell microencapsulating device for cell assembly technology. J Bioact Compat Polym 24(S1):48–62

    Google Scholar 

  7. Yao R, Zhang RJ, Yan YN, Wang XH (2009) In vitro angiogenesis of three-dimensional tissue engineered adipose tissues. J Bioact Compat Polym 24:5–24

    CAS  Google Scholar 

  8. Xu ME, Yan YN, Liu HX, Yao R, Wang XH (2009) Control adipose-derived stromal cells differentiation into adipose and endothelial cells in a 3-D structure established by cell-assembly technique. J Bioact Compat Polym 24(S1):31–47

    Article  Google Scholar 

  9. Xu ME, Yan YN, Liu HX, Yao R, Wang XH (2008)Establishing a multicellular model by three-dimensional cell-assembly technique for metabolic syndrome, Nature Precedings, Posted 8 Jan 2008

    Google Scholar 

  10. Wang XH, Yan YN, Zhang RJ (2007) Rapid prototyping as a tool for manufacturing bioartificial livers. Trends Biotechnol 25:505–513

    Article  CAS  Google Scholar 

  11. Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Deliv Rev 54:3

    Article  CAS  Google Scholar 

  12. Heimbach D, Luterman A, Burke J, Cram A, Hunt J, Jordan M, McManus M, Solem L, Warden G, Zawacki B (1998) Artificial dermis for major burn: a multi-center clinical trial. Ann Surg 208:313–320

    Article  Google Scholar 

  13. Chen WY, Abatangelo G (1999) Functions of hyaluronan in wound repair. Wound Repair Regen 7:79–89

    Article  CAS  Google Scholar 

  14. Veis A (1964) The macromolecular chemistry of gelatin. Academic, New York

    Google Scholar 

  15. Schacht EH, Nobels M, Vansteenkiste S, Demeester J, Fransen J, Lemahieu A (1993) Cross-linkage of gelatin by dextran dialdehyde. Polym Gels Netw 1:213–224

    Article  CAS  Google Scholar 

  16. Landers R, Hübner U, Schmelzeisen R, Mülhaupt R (2002) Rapid prototyping of scaffolds derived from thermoreversible hydrogels and tailored for application in tissue engineering. Biomaterials 23:4437–4447

    Article  CAS  Google Scholar 

  17. Govan JR, Fyfe JA, Jarman TR (1981) Isolation of alginate-producing mutants of Pseudomonas fluorescens, Pseudomonas putida and Pseudomonas mendocina. J Gen Microbiol 125(1):217–220

    CAS  Google Scholar 

  18. Bergel S (1909) On the functions of fibrins. Dtsch Med Wochenschr 35:633

    Article  Google Scholar 

  19. Ferry JD, Morrison PR (1946) Fibrin film and other products from human plasma. Ind Eng Chem 38:1217–1221

    Article  CAS  Google Scholar 

  20. Sastry TP, Rose C, Gomathinayagam S, Ganga R (1998) Chemically modified fibrin-gelatin composites: preparation and characterization. J Appl Polym Sci 68:1109–1115

    Article  CAS  Google Scholar 

  21. John P, Courts A (1977) The science and technology of gelatin. In: Ward AG, Courts A (eds) Academic Press, New York, p 138

    Google Scholar 

  22. Li SJ, Xiong Z, Wang XH, Yan YN, Liu HX, Zhang RJ (2009) Direct fabrication of a hybrid cell/hydrogel construct via a double-nozzle assembling technology. J Bioact Compat Polym 24:249–264

    Article  Google Scholar 

  23. Li SJ, Yan YN, Xiong Z, Weng CY, Zhang RJ, Wang XH (2009) Gradient hydrogel construct based on an improved cell assembling system. J Bioact Compat Polym 24(S1):84–99

    CAS  Google Scholar 

  24. Wang X, Yan Y, Xiong Z, Lin F, Wu R, Zhang R, Lu Q (2005) Preparation and evaluation of ammonia treated collagen/chitosan matrices for liver tissue engineering. J Biomed Mater Res- Part B, Appl Biomater 75(1):91–98

    Article  Google Scholar 

  25. Ong SM, Zhang C, Toh YC, Kim SH, Foo HL, Tan CH, van Noort D, Park S, Yu H (2008) A gel-free 3D microfluidic cell culture system. Biomaterials 29:3237–3244

    Article  CAS  Google Scholar 

  26. Colette S, Ranucci AK, Surendra PB, Prabhas VM (2000) Control of hepatocyte function on collagen foams: ­sizing matrix pores toward selective induction of 2-D and 3-D cellular morphogenesis. Biomaterials 21:783–793

    Article  Google Scholar 

  27. Fedorovich NE, Alblas J, de Vijn JR, Hennisnk WE, Verbout AJ, Dhert WJA (2007) Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing. Tissue Eng 13:1905–1925

    Article  CAS  Google Scholar 

  28. Kim SS, Sundback CA, Kaihara S, Benvenuto MS, Kim B, Mooney DJ, Vacanti JP (2000) Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system. Tissue Eng 6(1):39–44

    Article  CAS  Google Scholar 

  29. Richards FM, Knowles JR (1968) Glutaraldehyde as a protein crosslinking agent. J Mol Biol 37:231–233

    Article  CAS  Google Scholar 

  30. Bergel S (1909) On the functions of fibrins. Dtsch Med Wochenschr 35:633, Citedin-Mihaly Gerendas. Fibrin products as aids in hemostatis and wound healing. In: Koloman Laki. Fibrinogen. New York: Marcel Dekker Inc.; 1968. pp 277–316

    Article  Google Scholar 

  31. Schense JC, Hubbell JA (1999) Crosslinking exogenous bifunctional peptides into fibrin gels with factor XIIIa. Bioconjugate Chem 10(1):75–81

    Article  CAS  Google Scholar 

  32. Bruns H, Kneser U, Holzhüter S, Roth B, Kluth J, Kaufmann PM, Kluth D, Fiegel HC (2005) Injectable liver: a novel approach using fibrin gel as a matrix for culture and intrahepatic transplantation of hepatocytes. Tissue Eng 11:1718–1726

    Article  CAS  Google Scholar 

  33. Bryant SJ, Anseth KS (2002) Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. J Biomed Mater Res 59:63–72

    Article  CAS  Google Scholar 

  34. Kelm JM, Timmins NE, Brown CJ, Fussenegger M, Nielsen LK (2003) Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 83:173–180

    Article  CAS  Google Scholar 

  35. Tan W, Desa TA (2003) Microfluidic patterning of cells in extracellular matrix biopolymers: effects of channel size, cell type, and matrix composition on pattern integrity. Tissue Eng 9:255–267

    Article  CAS  Google Scholar 

  36. Cho SW, Song KW, Rhie JW, Park MH, Choi CY, Kim BS (2007) Engineered adipose tissue formation enhanced by basic fibroblast growth factor and a mechanically stable environment. Cell Transplant 16(4):421–434

    Google Scholar 

  37. Griffith LG, Naughton G (2002) Tissue engineering – current challenges and expanding opportunities. Science 295:1009–1014

    Article  CAS  Google Scholar 

  38. Patrick CW Jr (2000) Adipose tissue engineering: the future of breast and soft tissue reconstruction following tumor resection. Semin Sur Oncol 19:302–311

    Article  Google Scholar 

  39. Patrick CW Jr, Chauvin PB, Hobley J, Reece GP (1999) Preadipocytes seeded PLGA scaffolds for adipose tissue engineering. Tissue Eng 5:139–151

    Article  CAS  Google Scholar 

  40. von Heimburg D, Zachariah S, Heschel I, Kühling H, Schoof H, Hafemann B, Pallua N (2001) Human preadipocytes seeded on freeze-dried collagen scaffolds investigated in vitro and in vivo. Biomaterials 22:429–438

    Article  Google Scholar 

  41. von Heimburg D, Zachariah S, Low A, Pallua N (2001) Influence of different biodegradable carriers on the in vivo behavior of human adipose precursor cells. Plast Reconstr Surg 108:411–420

    Article  Google Scholar 

  42. Zuk PA et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    Article  CAS  Google Scholar 

  43. Despres JP, Lemieux I (2006) Abdominal obesity and metabolic syndrome. Nature 444:881–887

    Article  CAS  Google Scholar 

  44. Liu K, Yang YJ, Mansbridge J (2000) Comparison of the stress response to cryopreservation in monolayer and three-dimensional human fibroblast cultures: stress proteins, MAP kinases, and growth factor gene expression. Tissue Eng 6(5):539–554

    Article  CAS  Google Scholar 

  45. Sui SC, Wang XH, Liu PY, Yan YN, Zhang RJ (2009) Cryopreservation of 3D constructs based on a controlled cell assembling technology. J Bioact Compat Polym 24(5):5–19

    Article  Google Scholar 

  46. Lee J, Cuddihy MJ, Kotov NA (2008) Three-dimensional cell culture matrices: state of the art. Tissue Eng: Part B 14(1):61–86

    Article  CAS  Google Scholar 

  47. Blomback B, Bark N (2004) Fibrinopeptides and fibrin gel structure. Biophys Chem 112:147–151

    Article  Google Scholar 

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Correspondence to Xiaohong Wang .

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Wang, X., Yan, Y., Zhang, R. (2010). Gelatin-Based Hydrogels for Controlled Cell Assembly. In: Ottenbrite, R., Park, K., Okano, T. (eds) Biomedical Applications of Hydrogels Handbook. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5919-5_14

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