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Influence of solvent composition on the performance of carbodiimide cross-linked gelatin carriers for retinal sheet delivery

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Abstract

Gelatin is a protein molecule that displays bioaffinity and provides a template to guide retinal pigment epithelial (RPE) cell organization and growth. We have recently demonstrated that the carbodiimide cross-linked gelatin membranes can be used as retinal sheet carriers. The purpose of this work was to further determine the role of solvent composition in the tissue delivery performance of chemically modified biopolymer matrices. The gelatin molecules were treated with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) in the presence of binary ethanol/water mixtures with varying ethanol concentrations (70–95 vol%) to obtain the carriers with different cross-linking efficiencies and mechanical properties. Results of melting point measurements and in vitro degradation tests showed that when the cross-linking index reached a high level of around 45 %, the EDC cross-linked gelatin materials have sufficient thermal stability and resistance to enzymatic degradation, indicating their suitability for the development of carriers for retinal sheet delivery. Irrespective of the solvent composition, the chemically modified gelatin samples are compatible toward human RPE cells without causing toxicity and inflammation. In particular, the membrane carriers prepared by the cross-linking in the presence of solvent mixtures containing 80–90 vol% of ethanol have no impact on the proliferative capacity of ARPE-19 cultures and possess good efficiency in transferring and encapsulating the retinal tissues. It is concluded that, except for cell viability and pro-inflammatory cytokine expression, the retinal sheet delivery performance strongly depends on the solvent composition for EDC cross-linking of gelatin molecules.

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References

  1. Lu PL, Lai JY, Tabata Y, Hsiue GH. A methodology based on the “anterior chamber of rabbit eyes” model for noninvasively determining the biocompatibility of biomaterials in an immune privileged site. J Biomed Mater Res A. 2008;86:108–16.

    Google Scholar 

  2. Lai JY. The role of Bloom index of gelatin on the interaction with retinal pigment epithelial cells. Int J Mol Sci. 2009;10:3442–56.

    Article  CAS  Google Scholar 

  3. Hori K, Sotozono C, Hamuro J, Yamasaki K, Kimura Y, Ozeki M, et al. Controlled-release of epidermal growth factor from cationized gelatin hydrogel enhances corneal epithelial wound healing. J Control Release. 2007;118:169–76.

    Article  CAS  Google Scholar 

  4. Kuwahara K, Fang JY, Yang Z, Han B. Enzymatic crosslinking and degradation of gelatin as a switch for bone morphogenetic protein-2 activity. Tissue Eng Part A. 2011;17:2955–64.

    Article  CAS  Google Scholar 

  5. Montero RB, Vial X, Nguyen DT, Farhand S, Reardon M, Pham SM, et al. bFGF-containing electrospun gelatin scaffolds with controlled nano-architectural features for directed angiogenesis. Acta Biomater. 2012;8:1778–91.

    Article  CAS  Google Scholar 

  6. Jumblatt MM, Maurice DM, Schwartz BD. A gelatin membrane substrate for the transplantation of tissue cultured cells. Transplantation. 1980;29:498–9.

    Article  CAS  Google Scholar 

  7. McCulley JP, He YG, Meyer DR, Moore MB, Li JJ. In vitro transfer of rabbit corneal epithelium from carriers to denuded corneas or cryolathed lenticules. Cornea. 1991;10:466–77.

    Article  CAS  Google Scholar 

  8. Del Priore LV, Tezel TH, Kaplan HJ. Survival of allogeneic porcine retinal pigment epithelial sheets after subretinal transplantation. Invest Ophthalmol Vis Sci. 2004;45:985–92.

    Article  Google Scholar 

  9. Lai JY, Lu PL, Chen KH, Tabata Y, Hsiue GH. Effect of charge and molecular weight on the functionality of gelatin carriers for corneal endothelial cell therapy. Biomacromolecules. 2006;7:1836–44.

    Article  CAS  Google Scholar 

  10. Lai JY, Li YT. Functional assessment of cross-linked porous gelatin hydrogels for bioengineered cell sheet carriers. Biomacromolecules. 2010;11:1387–97.

    Article  CAS  Google Scholar 

  11. Lai JY, Chen KH, Hsu WM, Hsiue GH, Lee YH. Bioengineered human corneal endothelium for transplantation. Arch Ophthalmol. 2006;124:1441–8.

    Article  CAS  Google Scholar 

  12. Lai JY, Chen KH, Hsiue GH. Tissue-engineered human corneal endothelial cell sheet transplantation in a rabbit model using functional biomaterials. Transplantation. 2007;84:1222–32.

    Article  Google Scholar 

  13. Lai JY, Lin PK, Hsiue GH, Cheng HY, Huang SJ, Li YT. Low Bloom strength gelatin as a carrier for potential use in retinal sheet encapsulation and transplantation. Biomacromolecules. 2009;10:310–9.

    Article  CAS  Google Scholar 

  14. Lai JY, Li YT. Evaluation of cross-linked gelatin membranes as delivery carriers for retinal sheets. Mater Sci Eng, C. 2010;30:677–85.

    Article  CAS  Google Scholar 

  15. Lai JY, Li YT. Influence of cross-linker concentration on the functionality of carbodiimide cross-linked gelatin membranes for retinal sheet carriers. J Biomater Sci Polym Ed. 2011;22:277–95.

    Article  CAS  Google Scholar 

  16. Young JJ, Cheng KM, Tsou TL, Liu HW, Wang HJ. Preparation of cross-linked hyaluronic acid film using 2-chloro-1-methylpyridinium iodide or water-soluble 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide. J Biomater Sci Polym Ed. 2004;15:767–80.

    Article  CAS  Google Scholar 

  17. Tomihata K, Ikada Y. Cross-linking of gelatin with carbodiimides. Tissue Eng. 1996;2:307–13.

    Article  CAS  Google Scholar 

  18. Choi YS, Hong SR, Lee YM, Song KW, Park MH, Nam YS. Study on gelatin-containing artificial skin: I. Preparation and characteristics of novel gelatin-alginate sponge. Biomaterials. 1999;20:409–17.

    Article  CAS  Google Scholar 

  19. Hsiue GH, Lai JY, Lin PK. Absorbable sandwich-like membrane for retinal-sheet transplantation. J Biomed Mater Res. 2002;61:19–25.

    Article  CAS  Google Scholar 

  20. Ma DHK, Lai JY, Cheng HY, Tsai CC, Yeh LK. Carbodiimide cross-linked amniotic membranes for cultivation of limbal epithelial cells. Biomaterials. 2010;31:6647–58.

    Article  CAS  Google Scholar 

  21. Lai JY. Evaluation of cross-linking time for porous gelatin hydrogels on cell sheet delivery performance. J Mech Med Biol. 2011;11:967–81.

    Article  Google Scholar 

  22. Lai JY, Li YT, Wang TP. In vitro response of retinal pigment epithelial cells exposed to chitosan materials prepared with different cross-linkers. Int J Mol Sci. 2010;11:5256–72.

    Article  CAS  Google Scholar 

  23. Lai JY, Tu IH. Adhesion, phenotypic expression, and biosynthetic capacity of corneal keratocytes on surfaces coated with hyaluronic acid of different molecular weights. Acta Biomater. 2012;8:1068–79.

    Article  CAS  Google Scholar 

  24. Lu PL, Lai JY, Ma DHK, Hsiue GH. Carbodiimide cross-linked hyaluronic acid hydrogels as cell sheet delivery vehicles: characterization and interaction with corneal endothelial cells. J Biomater Sci Polym Ed. 2008;19:1–18.

    Article  Google Scholar 

  25. Lai JY. Biocompatibility of chemically cross-linked gelatin hydrogels for ophthalmic use. J Mater Sci Mater Med. 2010;21:1899–911.

    Article  CAS  Google Scholar 

  26. Lai JY. Solvent composition is critical for carbodiimide cross-linking of hyaluronic acid as an ophthalmic biomaterial. Materials. 2012;5:1986–2002.

    Article  CAS  Google Scholar 

  27. Lai JY, Ma DHK, Cheng HY, Sun CC, Huang SJ, Li YT, et al. Ocular biocompatibility of carbodiimide cross-linked hyaluronic acid hydrogels for cell sheet delivery carriers. J Biomater Sci Polym Ed. 2010;21:359–76.

    Article  CAS  Google Scholar 

  28. Lai JY, Li YT, Cho CH, Yu TC. Nanoscale modification of porous gelatin scaffolds with chondroitin sulfate for corneal stromal tissue engineering. Int J Nanomed. 2012;7:1101–14.

    Article  CAS  Google Scholar 

  29. Lai JY, Hsieh AC. A gelatin-g-poly(N-isopropylacrylamide) biodegradable in situ gelling delivery system for the intracameral administration of pilocarpine. Biomaterials. 2012;33:2372–87.

    Article  CAS  Google Scholar 

  30. Lai JY, Wang TP, Li YT, Tu IH. Synthesis, characterization and ocular biocompatibility of potential keratoprosthetic hydrogels based on photopolymerized poly(2-hydroxyethyl methacrylate)-co-poly(acrylic acid). J Mater Chem. 2012;22:1812–23.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by Grant NSC100-2628-E-182-004-MY3 from the National Science Council of Republic of China and grant CMRPD2A0111 from Chang Gung Memorial Hospital. The author is grateful to Mr. I-Hao Tu (Institute of Biochemical and Biomedical Engineering, Chang Gung University) for technical assistance.

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Authors and Affiliations

  1. Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan, Republic of China

    Jui-Yang Lai

  2. Biomedical Engineering Research Center, Chang Gung University, Taoyuan, 33302, Taiwan, Republic of China

    Jui-Yang Lai

  3. Molecular Medicine Research Center, Chang Gung University, Taoyuan, 33302, Taiwan, Republic of China

    Jui-Yang Lai

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Correspondence to Jui-Yang Lai.

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Lai, JY. Influence of solvent composition on the performance of carbodiimide cross-linked gelatin carriers for retinal sheet delivery. J Mater Sci: Mater Med 24, 2201–2210 (2013). https://doi.org/10.1007/s10856-013-4961-y

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  • DOI: https://doi.org/10.1007/s10856-013-4961-y

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