Synthesis of a chitosan derivative soluble at neutral pH and gellable by freeze–thawing, and its application in wound care

• Published in: Acta biomaterialia 2012-02, Vol.8 (2), p.686-693
• Main Authors: Takei, T., Nakahara, H., Ijima, H., Kawakami, K.
• Format: Article
• Language: English
• Subjects: additives; adhesion; Animals; antigens; aqueous solutions; Cell Adhesion - drug effects; Cell Survival - drug effects; Cells, Cultured; Chickens; Chitosan; Chitosan - chemical synthesis; Chitosan - chemistry; Chitosan - pharmacology; Cryogel; Cryogels - chemistry; fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Freeze–thawing; Freezing; gels; Gluconates - chemical synthesis; Gluconates - chemistry; Humans; hydrocolloids; Hydrogen-Ion Concentration - drug effects; lysozyme; Male; Mice; Muramidase - metabolism; Nephelometry and Turbidimetry; neutrophils; Polymorphonuclear leukocyte; proteins; Rats; Solubility - drug effects; Solutions; Spectroscopy, Fourier Transform Infrared; tissue repair; toxic substances; viability; Wound dressing; Wound Healing - drug effects
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2011.10.005

Conventional chitosan hydrogels exhibit an acidic nature and contain unfavorable additives because (i) chitosan is soluble only in acidic solutions and (ii) toxic chemicals or proteins of non-human origin that serve as antigens are necessary for preparing chitosan hydrogels. These characteristics of the chitosan hydrogels limit their possibilities as wound dressings. In this study, a chitosan–gluconic acid conjugate is developed, soluble in an aqueous solution at neutral pH and gellable by freeze–thawing (cryogelation) without using additives. The viability of L929 fibroblasts cultured in the presence of the chitosan derivative for 24 h was >96%. The degradation rate of the corresponding chitosan cryogels by lysozyme was tunable via the derivative concentration in the gels. The gels had low cellular adhesiveness. The gels promoted the accumulation of inflammatory cells such as polymorphonuclear leukocytes, which have the potential to release chemical mediators effective for wound healing, in full-thickness skin wounds in rats and accelerated the healing of the wounds. These results demonstrate that cryogels are promising for wound care.