Effect of Viscous Injectable Pure Alginate Sol on Cultured Fibroblasts

Background: Alginates have a wide variety of potential clinical applications, including use in cell encapsulation, drug delivery, and tissue engineering. Although the compounds are typically used in the form of a calcium hydrogel, alginates in this form possess several disadvantages, including low biodegradability, induction of foreign body reactions, and cytotoxicity secondary to Ca2+ efflux and contamination with bioincompatible substances. Thus, the goal of the present study was to develop a new method of obtaining sterilized, pure, highly viscous alginate sol from seaweed alginates and to determine its utility as an injectable antiadhesion drug. Methods: Viscous injectable pure alginate sol was produced from a commercially available sodium alginate, and its molecular and physical characteristics were analyzed. The biological properties of the viscous injectable pure alginate sol were analyzed using cultured fibroblasts prepared from the dorsal skin of neonatal rats to determine its biocompatibility and its effects on cell proliferation, cell migration, and collagen lattice contraction. Results: The mannuronic acid–to–glucuronic acid ratio of viscous injectable pure alginate sol, as determined by nuclear magnetic resonance studies, was 1.2, and its viscosity at 5 percent was 17,800 mPa. Purification used to produce viscous injectable pure alginate sol decreased contamination by insoluble particles by 20 percent and decreased polyphenol concentration by 17 percent. In vitro analyses with cultured fibroblasts demonstrated that viscous injectable pure alginate sol had excellent biodegradability and biocompatibility and that viscous injectable pure alginate sol inhibited fibroblast proliferation and migration. Furthermore, assessment of collagen contraction with floating fibroblast-loaded collagen lattices indicated that viscous injectable pure alginate sol enhanced wound healing in surrounding connective tissues. Conclusions: The authors conclude that viscous injectable pure alginate sol can inhibit scar formation by presenting a physical barrier to invading fibroblasts and by enhancing wound healing of surrounding tissues.

[1]  Y. Suzuki,et al.  In vivo evaluation of a novel alginate dressing. , 1999, Journal of biomedical materials research.

[2]  S. Thomas,et al.  Alginate dressings in surgery and wound management--Part 1. , 2000, Journal of wound care.

[3]  C. Ide,et al.  Peripheral nerve regeneration through alginate gel: analysis of early outgrowth and late increase in diameter of regenerating axons , 2002, Experimental Brain Research.

[4]  Frederick Grinnell,et al.  Fibroblasts, myofibroblasts, and wound contraction , 1994, The Journal of cell biology.

[5]  Bjørn Larsen,et al.  13C-n.m.r. studies of monomeric composition and sequence in alginate , 1981 .

[6]  D. Lauffenburger,et al.  Epidermal growth factor induces acute matrix contraction and subsequent calpain‐modulated relaxation , 2002, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[7]  K. Smetana Cell biology of hydrogels. , 1993, Biomaterials.

[8]  Masayoshi Ohta,et al.  Alginate enhances elongation of early regenerating axons in spinal cord of young rats. , 2004, Tissue engineering.

[9]  M. Rosdy,et al.  Cytotoxicity testing of wound dressings using normal human keratinocytes in culture. , 1990, Journal of biomedical materials research.

[10]  S. Valla,et al.  Bacterial alginates: biosynthesis and applications , 1997, Applied Microbiology and Biotechnology.

[11]  A. Lansdown,et al.  An evaluation of the local reaction and biodegradation of calcium sodium alginate (Kaltostat) following subcutaneous implantation in the rat. , 1994, Journal of the Royal College of Surgeons of Edinburgh.

[12]  T. Nakamura,et al.  Evaluation of a novel alginate gel dressing: cytotoxicity to fibroblasts in vitro and foreign-body reaction in pig skin in vivo. , 1998, Journal of biomedical materials research.

[13]  D. Craig,et al.  Characterization of the Block Structure and Molecular Weight of Sodium Alginates , 1997, The Journal of pharmacy and pharmacology.

[14]  F. Thürmer,et al.  Biocompatible alginate from freshly collected Laminaria pallida for implantation , 2000, Applied Microbiology and Biotechnology.

[15]  F. Grinnell,et al.  Fibroblast-collagen-matrix contraction: growth-factor signalling and mechanical loading. , 2000, Trends in cell biology.