ABSTRACT A variety of skin substitutes are used in the treatment of full-thickness burns. Substitutes made from skin can harbor latent viruses, and artificial skin grafts can heal with extensive scarring, failing to regenerate structures such as glands, nerves, and hair follicles. Biodegradable and biocompatible hydrogels, however, rarely mimic the strength of the epidermis. Therefore, novel and practical skin scaffold materials remain to be developed. Polysaccharides form hydrogels with predicted inherent biocompatibility. This paper describes the preparation and biocompatibility of unique hydrogel skin scaffolds from plant-extracted polysaccharide mixtures of specific sources, types, and molecular weight fractions. These hydrogels have a range of mechanical and degradation properties with the potential to fulfill the multiple, diverse functions of artificial skin, including protection, compatibility with different cell types, biodegradation, and release of needed signals for cell growth and wound healing.
Cite this paper
nullS. Juris, A. Mueller, B. Smith, S. Johnston, R. Walker and R. Kross, "Biodegradable Polysaccharide Gels for Skin Scaffolds," Journal of Biomaterials and Nanobiotechnology, Vol. 2 No. 3, 2011, pp. 216-225. doi: 10.4236/jbnb.2011.23027.
 E. Fuchs and S. Raghavan, “Getting under the skin of epidermal morphogenesis,” Nature Reviews Genetics, Vol. 3, No. 3, 2002, pp. 199-209.
 J. Kanitakis, “Anatomy, histology and immunohistochemistry of normal human skin,” European Journal of Dermatology, Vol. 12, No. 4, 2002, pp. 390-399.
 P. Martin, “Wound healing--aiming for perfect skin regeneration,” Science, Vol. 276, No. 5309, 1997, pp. 75-81.
 S. T. Boyce, “Design principles for composition and performance of cultured skin substitutes,” Burns, Vol. 27, No. 5, 2001, pp. 523-533.
 R. Odessey, “Addendum: multicenter experience with cultured epidermal autograft for treatment of burns,” Journal of Burn Care and Rehabilitation, Vol. 13, No. 1, 1992, pp. 174-180.
 M. R. Pittelkow and R. E. Scott, “New techniques for the in vitro culture of human skin keratinocytes and perspectives on their use for grafting of patients with extensive burns,” Mayo Clinic Proceedings, Vol. 61, No. 10, 1986, pp. 771-777.
 J. S. Williamson, C. F. Snelling, P. Clugston, I. B. Macdonald and E. Germann, “Cultured epithelial autograft: five years of clinical experience with twenty-eight patients,” The Journal of Trauma, Vol. 39, No. 2, 1995, pp. 309-319.
 C. A. Jahoda, R. F. Oliver, A. J. Reynolds, J. C. Forrester and K. A. Horne, “Human hair follicle regeneration following amputation and grafting into the nude mouse,” Journal of Investigative Dermatology, Vol. 107, No. 6, 1996, pp. 804-807.
 D. W. Hutmacher, K. W. Ng and H. L. Khor, “Skin Tissue Engineering, Part I - Review,” in Biodegradable Systems in Tissue Engineering and Regenerative Medicine, R. L. Reis and J. S. Roman Eds., CRC Press, Boca Raton, FL, 2005, pp. 601-625.
 J. Mansbridge, “Tissue-engineered skin substitutes,” Expert Opinion on Biological Therapy, Vol. 2, No. 1, 2002, pp. 25-34.
 B. S. Atiyeh, J. Ioannovich, C. A. Al-Amm and K. A. El-Musa, “Management Of Acute And Chronic Open Wounds: The Importance Of Moist Environment In Optimal Wound Healing,” Current Pharmaceutical Biotechnology, Vol. 3, No. 3, 2002, pp. 179-195.
 B. S. Atiyeh, J. Ioannovich, C. A. Al-Amm, K. A. El-Musa and R. Dham, “Improving Scar Quality: A Prospective Clinical Study,” Aesthetic Plastic Surgery, Vol. 26, No. 6, 2002, pp. 470-476.
 L. L. Bolton, K. Monte and L. A. Pirone, “Moisture and Healing: Beyond the Jargon,” Ostomy Wound Management, Vol. 46, No. 1A Suppl, 2000, pp. 51S-62S.
 G. D. Winter and J. T. Scales, “Effect of Air Drying and Dressings on the Surface of a Wound,” Nature, Vol. 197, No. 4862, 1963, pp. 91-92.
 P. Mainil-Varlet, P. Rahn and S. Gogolewski, “Long-Term in-vivo Degradation and Bone Reaction to Various Polylactides 1. One-Year Results,” Biomaterials, Vol. 18, No. 3, 1997, pp. 257-266.
 J. C. Meredith and E. J. Amis, “LCST Phase Separation in Biodegradable Polymer Blends: Poly(D,L-lactide) and Poly(e-caprolactone),” Macromolecular Chemistry and Physics, Vol. 201, No. 6, 2000, pp. 733-739.
 A. M. Reed and D. K. Gilding, “Biodegradable Polymers for Use in Surgery - Poly(glycolic)/poly(lactic acid) Homo- and Copolymers: 2. In-vitro Degradation,” Polymer, Vol. 22, No. 4, 1981, pp. 494-498.
 D. Tian, Ph. Dubois, R. Jerome and Ph. Teyssie, “Macromolecular Engineering of Polylactones and Polylactides. 18. Synthesis of Star-Branched Aliphatic Polyesters Bearing Various Functional End Groups,” Macromolecules, Vol. 27, No. 15, 1994, pp. 4134-4144.
 M. Vert, S. M. Li, G. Spenlehauer and P. Guerin, “Bioresorbability and biocompatibility of aliphatic polyesters,” Journal of Materials Science: Materials in Medicine, Vol. 3, No. 6, 1992, pp. 432-436.
 K. Fu, A, M. Klibanov and R. Langer, “Protein Stability in Controlled-Release Systems,” Nature Biotechnology, Vol. 18, No. 1, 2000, pp. 24-26.
 K. Fu, D. W. Pack, A. M. Klibanov and R. Langer, “Visual Evidence of Acidic Environment Within Degrading Poly(Lactic-co-Glycolic Acid) (PLGA) Microspheres,” Pharmaceutical Research, Vol. 17, No. 1, 2000, pp. 100-106.
 C. G. Pitt, M. M. Gratzl, G. L. Kimmel, J. Surles and A. Schindler, “Aliphatic Polyesters: II. The Degradation of Poly(D,L-lactide), Poly(e-caprolactone), and their Copolymers in vivo,” Biomaterials, Vol. 2, No. 4, 1981, pp. 215-220.
 M. Rinaudo, “Advances in Characterization of Polysaccharides in Aqueous Solution and Gel State,” in Polysaccharides: Structural Diversity and Functional Versatility, S. Dumitriu Ed., Marcel Dekker, New York, 2005, pp. 237-252.
 J. O. Carnali, “Gelation in physically associating biopolymer systems,” Rheologica Acta, Vol. 31, No. 5, 1992, pp. 399-412.
 N. Ikawa, “Mechanical relaxation of hydrogel. IV. Dynamic viscoelastic properties of konjac mannan gum,” Bulletin of the Faculty of Agriculture - Meiji University, Vol. 70, 1985, pp. 33-43.
 M. Rinaudo, R. Auzely, C. Vallin and I. Mullagaliev, “Specific Interactions in Modified Chitosan Systems,” Biomacromolecules, Vol. 6, No. 5, 2005, pp. 2396-2407.
 T. Sato, T. Norisuye and H. Fujita, “Double-Stranded Helix of Xanthan: Dimensional and Hydrodynamic Properties in 0.1 M Aqueous Sodium Chloride,” Macromolecules, Vol. 17, No. 12, 1984, pp. 2696-2700.
 F. van de Velde and G. A. De Ruiter, “Carrageenan,” in Polysaccharides and Polyamides in the Food Industry: Properties, Production, and Patents, A. Steinbuechel and S. K. Rhee Eds., Weinheim: Wiley-VCH, Verlag, 2005, pp. 85-114.
 T. Yui and K. Ogawa, “X-ray Diffraction Study of Polysaccharides,” in Polysaccharides: Structural Diversity and Functional Versatility, S. Dumitriu Ed., Marcel Dekker, New York, 2005, pp. 99-122.
 M. Thanou and H. E. Junginger, “Pharmaceutical Applications of Chitosan and Derivatives,” in Polysaccharides: Structural Diversity and Functional Versatility, S. Dumitriu Ed., Marcel Dekker, New York, 2005, pp. 661-678.
 G. G. Gallico, N. E. O'Connor, C. C. Compton, O. Kehinde and H. Green, “Permanent coverage of large burn wounds with autologous cultured human epithelium,” New England Journal of Medicine, Vol. 311, No. 7, 1984, pp. 448-451.
 M. Bootman and R. Yamamoto, Integra Lifesciences I, Ltd, assignee, “Polyurethane-Biopolymer Composite,” USA patent, 6,596, 293. 2000 07/22/03.
 A. G. A. Coombes, E. Verderio, B. Shaw, X. Li, M. Griffin and S. Downes, “Biocomposites of Non-Crosslinked Natural and Synthetic Polymers,” Biomaterials, Vol. 23, No. 10, 2002, pp. 2113-2118.
 D. Wisser and J. Steffes, “Skin Replacement with a Collagen Based Dermal Substitute, Autologous Keratinocytes and Fibroblasts in Burn Trauma,” Burns, Vol. 29, No. 4, 2003, pp. 375-380.
 H. Li, Y. Liu, X. Z. Shu, S. D. Gray and G. D. Prestwich, “Synthesis and Biological Evaluation of a Cross-Linked Hyaluron-Mitomycin C Hydrogel,” Biomacromolecules, Vol. 5, No. 3, 2004, pp. 895-902.
 R. A. Peattie, A. P. Nayate, M. A. Firpo, J. Shelby, R. J. Fisher and G. D. Prestwich, “Stimulation of In Vivo Angiogenesis by Cytokine-Loaded Hyaluronic Acid Hydrogel Implants,” Biomaterials, Vol. 25, No. 14, 2004, pp. 2789-2798.
 X. Z. Shu, Y. Liu, F. S. Palumbo, Y. Luo and G. D. Prestwich, “In Situ Crosslinkable Hyaluron Hydrogels for Tissue Engineering,” Biomaterials, Vol. 25, No. 7-8, 2004, pp. 1339-1348.
 F. L. Mi, S. S. Shyu, Y. M. Lin, Y. B. Wu, C. K. Peng and Y. H. Tsai, “Chitin/PLGA Blend Microspheres as a Biodegradable Drug Delivery System: A New Delivery System for Protein,” Biomaterials, Vol. 24, No. 27, 2003, pp. 5023-5036.
 J. F. Mano, N. M. Neves and R. L. Reis, “Mechanical Characterization of Biomaterials,” in Biodegradable Systems in Tissue Engineering and Regenerative Medicine, R. L. Reis and J. S. Roman Eds., CRC Press, Boca Raton, FL, 2005, pp. 152-174.
 M. P. Pavlov, J. F. Mano, N. M. Neves and R. L. Reis, “Fibers and 3D Mesh Scaffolds from Biodegradable Starch-Based Blends: Production and Characterization,” Macromolecular Bioscience, Vol. 4, No. 8, 2004, pp. 776-783.
 R. D. Kross, “Method for Using Glycol Additives to Texturally Modify Natural Gum Hydrogels,” USA patent, 6,664,301. 2003.
 OECD, “OECD Principles of GLP,” ENV/MC/CHEM, Vol. 404, OECD, Paris, 1997.
 J. Durando, “Primary Skin Irritation Study in Rabbits: Eurofins PSL,” 2010, Report nr 28823.
 J. H. Draize, G. Woodward and H. O. Calvery, “Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes,” Journal of Pharmacology and Experimental Therapeutics, Vol. 82, No. 3, 1944, pp. 377-390.
 OECD, “Ready Biodegradability: Closed Bottle Test,” OECD Guideline for Testing of Chemicals. Vol. 301D, 2003.
 D. Detlef, “Assessment of the Ready Biodegradability of Polysaccharide Hydrogel with the Closed Bottle Test: Eurofins GAB,” 2010.
 R. Silverstein, G. Bassler and T. Morrill, “Spectrometric Identification of Organic Compounds,” John Wiley & Sons, New York, 1991.