Evaluation of antibiotic-loaded collagen-hyaluronic acid matrix as a skin substitute.

The 1-ethyl-(3-3-dimethylaminopropyl) carbodiimide hydrochloride-crosslinked collagen-hyaluronic acid (HA) matrices containing tobramycin or ciprofloxacin as an antibiotic agent were fabricated for the control of wound contamination and characterized with respect to morphology, mechanical strength, in vitro release, antibacterial activity and cytotoxicity. For the tobramycin loaded matrix, the antibacterial capacity increased with the drug loading. Tobramycin and ciprofloxacin loaded matrices maintained their antibacterial effects for over 96 and 48 h, respectively. However, cell viability testing revealed that 0.4 mg/ml of ciprofloxacin has a cytotoxic effect on fetal human dermal fibroblasts. The effects of the bilayered collagen-HA matrices containing tobramycin and growth factors were also evaluated using an in vivo full thickness dermal defect model. Though the tobramycin incorporated collagen-HA matrix had no significant effect on wound healing compared with the control, the tobramycin incorporated matrix containing basic fibroblast growth factor or platelet-derived growth factor significantly enhanced wound healing. This study demonstrates the potential efficacy of crosslinked collagen-HA matrix containing antibiotics and growth factors for defective skin tissue replacement and infection prevention.

[1]  Jong-Chul Park,et al.  Laminin modified infection-preventing collagen membrane containing silver sulfadiazine-hyaluronan microparticles. , 2002, Artificial organs.

[2]  A. Singer,et al.  Cutaneous wound healing. , 1999, The New England journal of medicine.

[3]  I. Larripa,et al.  Chromosomal aberrations in human lymphocytes exposed in vitro to enrofloxacin and ciprofloxacin. , 1999, Toxicology letters.

[4]  I. Namikawa,et al.  Binding of Host‐Associated Treponeme Proteins to Collagens and Laminin: A Possible Mechanism of Spirochetal Adherence to Host Tissues , 1994, Microbiology and immunology.

[5]  B. Westerlund,et al.  Bacterial proteins binding to the mammalian extracellular matrix , 1993, Molecular microbiology.

[6]  M. Melia,et al.  Effect of topical ciprofloxacin 0.3% and ofloxacin 0.3% on the reduction of bacterial flora on the human conjunctiva , 2000, Journal of cataract and refractive surgery.

[7]  G. Stern,et al.  Effect of topical antibiotic solutions on corneal epithelial wound healing. , 1983, Archives of ophthalmology.

[8]  G. Reid,et al.  Effects of ciprofloxacin, norfloxacin, and ofloxacin on in vitro adhesion and survival of Pseudomonas aeruginosa AK1 on urinary catheters , 1994, Antimicrobial Agents and Chemotherapy.

[9]  W. D. de Vos,et al.  Multiparametric Flow Cytometry and Cell Sorting for the Assessment of Viable, Injured, and Dead Bifidobacterium Cells during Bile Salt Stress , 2002, Applied and Environmental Microbiology.

[10]  D. H. Lee,et al.  Antibacterial effect of antibiotic solution on cellular viability in canine veins. , 2001, Artificial Organs.

[11]  L. Marton,et al.  Liquid-chromatographic determination of tobramycin in serum with spectrophotometric detection. , 1983, Clinical chemistry.

[12]  G. Abatangelo,et al.  Functions of hyaluronan in wound repair , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[13]  Y. Ikada,et al.  Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities. , 1999, Biomaterials.

[14]  M. Plotkowski,et al.  Differential adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells in primary culture. , 1991, The Journal of clinical investigation.

[15]  Si-Nae Park,et al.  Biological characterization of EDC-crosslinked collagen-hyaluronic acid matrix in dermal tissue restoration. , 2003, Biomaterials.

[16]  N. Khardori,et al.  Modulation of biofilms of Pseudomonas aeruginosa by quinolones , 1995, Antimicrobial agents and chemotherapy.

[17]  Jong-Chul Park,et al.  An infection-preventing bilayered collagen membrane containing antibiotic-loaded hyaluronan microparticles: physical and biological properties. , 2002, Artificial organs.

[18]  R. D. Isaacs.  Borrelia burgdorferi bind to epithelial cell proteoglycans. , 1994, The Journal of clinical investigation.

[19]  S. Boyce,et al.  Cytotoxicity testing of topical antimicrobial agents on human keratinocytes and fibroblasts for cultured skin grafts. , 1995, The Journal of burn care & rehabilitation.

[20]  I. Yannas,et al.  Design of an artificial skin. I. Basic design principles. , 1980, Journal of biomedical materials research.

[21]  M. Egerbacher,et al.  Effects of enrofloxacin and ciprofloxacin hydrochloride on canine and equine chondrocytes in culture. , 2001, American journal of veterinary research.

[22]  L. Dahners,et al.  Bone Toxicity of Locally Applied Aminoglycosides , 1995, Journal of orthopaedic trauma.

[23]  C. Perry,et al.  Local delivery of antibiotics via an implantable pump in the treatment of osteomyelitis. , 1988, Clinical orthopaedics and related research.

[24]  J. Barbeau,et al.  Multiparametric analysis of waterline contamination in dental units , 1996, Applied and environmental microbiology.

[25]  E. Trafny,et al.  Effects of free and liposome-encapsulated antibiotics on adherence of Pseudomonas aeruginosa to collagen type I , 1995, Antimicrobial agents and chemotherapy.

[26]  I. K. Cohen,et al.  Platelet-derived growth factor induces fetal wound fibrosis. , 1994, Journal of pediatric surgery.

[27]  L. Phillips,et al.  Recombinant Human Platelet-derived Growth Factor-BB for the Treatment of Chronic Pressure Ulcers , 1992, Annals of plastic surgery.

[28]  M. Franz,et al.  Initiating the inflammatory phase of incisional healing prior to tissue injury. , 2000, The Journal of surgical research.

[29]  Jerome J. Schentag,et al.  High-pressure liquid chromatography analysis and single-dose disposition of tobramycin in human volunteers , 1980, Antimicrobial Agents and Chemotherapy.

[30]  K. Lewis,et al.  Biofilms and Planktonic Cells of Pseudomonas aeruginosa Have Similar Resistance to Killing by Antimicrobials , 2001, Journal of bacteriology.

[31]  Tetsu Sasaki,et al.  The Effects of Basic Fibroblast Growth Factor and Doxorubicin on Cultured Human Skin Fibroblasts: Relevance to Wound Healing , 1992, The Journal of dermatology.

[32]  D. Gilbert,et al.  Phenotypic Resistance of Staphylococcus aureus, Selected Enterobacteriaceae, and Pseudomonas aeruginosa after Single and Multiple In Vitro Exposures to Ciprofloxacin, Levofloxacin, and Trovafloxacin , 2001, Antimicrobial Agents and Chemotherapy.

[33]  Min Jung Song,et al.  Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking. , 2002, Biomaterials.

[34]  M. A. Nelson,et al.  Liquid chromatographic determination of amikacin in serum with spectrophotometric detection. , 1984, Journal of chromatography.

[35]  G F Pierce,et al.  Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair. , 1992, The American journal of pathology.

[36]  B. Dunkin,et al.  Effect of growth factors on cell proliferation and epithelialization in human skin. , 1995, The Journal of surgical research.