JBNB  Vol.3 No.4 A , October 2012
Antimicrobial Activity of Minocycline-Loaded Genipin-Crosslinked Nano-Fibrous Chitosan Mats for Guided Tissue Regeneration
ABSTRACT
Antimicrobial delivery has been advocated for guided tissue regeneration (GTR) or guided bone regeneration (GBR) therapies involving patients with aggressive or unresolved periodontitis/peri-implantitis. Electrospun chitosan membranes demonstrate several advantages over traditional GTR barrier membranes because they stimulate healing, mimic the topology of the extracellular matrix, and allow for diffusion of nutrients and wastes into/out of the graft site, and were shown to stimulate bone formation in a rabbit calvarial criticalsize defect model. Previously, we have shown improvements in mechanical properties and degradation kinetics by crosslinking electrospun membranes with 5 mM or 10 mM genipin. We have also demonstrated the ability of elecrospun chitosan membranes to inhibit lippopolysaccharide (LPS)-induced monocyte activation. In this study, minocycline was incorporated into the chitosan membrane by passive absorption at 5 or 10 mg/mL. The minocycline-loaded membranes and control membranes (carrier only) were tested against Porphyromonas gingivalis (P. gingivalis) by repeated zone of inhibition (ZOI) measurements. Testing showed that uncrosslinked and genipin-crosslinked membranes have similar capacity to absorb aqueous solutions (swelling ratio 1.7 - 2.2). Minocycline loading resulted in bacterial inhibition for up to 8 days from crosslinked membranes (with 11 mm initial ZOI) whereas uncrosslinked membranes loaded with minocycline only inhibited bacteria for 4 days (with 8 mm initial ZOI). These in vitro results suggest that genipin-crosslinked electrospun chitosan membranes loaded with minocycline may be able to reduce early bacterial contamination of GTR graft sites.

Cite this paper
P. Norowski, J. Babu, P. Adatrow, F. Garcia-Godoy, W. Haggard and J. Bumgardner, "Antimicrobial Activity of Minocycline-Loaded Genipin-Crosslinked Nano-Fibrous Chitosan Mats for Guided Tissue Regeneration," Journal of Biomaterials and Nanobiotechnology, Vol. 3 No. 4, 2012, pp. 528-532. doi: 10.4236/jbnb.2012.324054.
References
[1]   S. M. Kuo, S. J. Chang, T. W. Chen and T. C. Kuan, “Guided Tissue Regeneration for Using a Chitosan Membrane: An Experimental Study in Rats,” Journal of Biomedical Materials Research Part A, Vol. 76, No. 2, 2006, pp. 408-415. doi:10.1002/jbm.a.30534

[2]   S. Y. Shin, H. N. Park, K. H. Kim, M. H. Lee, Y. S. Choi, Y. J. Park, Y. M. Lee, Y. Ku, I. C. Rhyu, S. B. Han, S. J. Lee and C. P. Chung, “Biological Evaluation of Chitosan Nanofiber Membrane for Guided Bone Regeneration,” Journal of Periodontology, Vol. 76, No. 10, 2005, pp. 1778- 1784. doi:10.1902/jop.2005.76.10.1778

[3]   Y. J. Yeo, D. W. Jeon, C. S. Kim, S. H. Choi, K. S. Cho, Y. K. Lee and C. K. Kim, “Effects of Chitosan Nonwoven Membrane on Periodontal Healing of Surgically Created One-Wall Intrabony Defects in Beagle Dogs,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 72, No. 1, 2005, pp. 86-93. doi:10.1002/jbm.b.30121

[4]   T. Matsunaga, K. Yanagiguchi, S. Yamada, N. Ohara, T. Ikeda and Y. Hayashi, “Chitosan Monomer Promotes Tissue Regeneration on Dental Pulp Wounds,” Journal of Biomedical Materials Research Part A, Vol. 76, No. 4, 2005, pp. 711-720.

[5]   H. J. Yoon, M. E. Moon, H. S. Park, S. Y. Im and Y. H. Kim, “Chitosan Oligo-saccharide (COS) Inhibits LPS-Induced Inflammatory Effects in RAW 264.7 Macrophage Cells,” Biochemical and Biophysical Research Communications, Vol. 358, No. 3, 2007, pp. 954-959. doi:10.1016/j.bbrc.2007.05.042

[6]   K.-S. Nam, M.-K. Kim and Y.-H. Shon, “Inhibition of Proinflammatory Cytokine-Induced Invasiveness of HT-29 Cells by Chitosan Oligo-saccharide,” Journal of Microbiology and Biotechnology, Vol. 17, No. 12, 2007, pp. 2042-2045.

[7]   F. Chen, X. Li, X. Mo, C. He, H. Wang and Y. Ikada, “Electrospun Chitosan-P(LLA-CL) Nanofibers for Biomimetic Extracellular Matrix,” Journal of Biomaterials Science, Vol. 19, No. 5, 2008, pp. 677-691. doi:10.1163/156856208784089661

[8]   Y. Z. Cai, L. L. Wang, H. X. Cai, Y. Y. Qi, X. H. Zou and H. W. Ouyang, “Electrospun Nanofibrous Matrix Improves the Regeneration of Dense Cortical Bone,” Journal of Biomedical Materials Research Part A, Vol. 95, No. 1, 2010, pp. 49-57. doi:10.1002/jbm.a.32816

[9]   P. Norowski, University of Memphis, 2011.

[10]   P. A. Norowski, S. Mishra, P. C. Adatrow, W. O. Haggard and J. D. Bumgardner, “Suture Pullout Strength and in Vitro Fibroblast and RAW 264.7 Monocyte Biocompatibility of Genipin Crosslinked Nanofibrous Chitosan Mats for Guided Tissue Regeneration,” Journal of Biomedical Materials Research Part A, Vol. 100A, No. 11, 2012, pp. 2890-2896. doi:10.1002/jbm.a.34224

[11]   D. Ugar-Cankal and N. Ozmeric, “A Multifaceted Molecule, Nitric Oxide in Oral and Periodontal Diseases,” Clinica Chimica Acta, Vol. 366, No. 1-2, 2006, pp. 90-100. doi:10.1016/j.cca.2005.10.018

[12]   F. Daghigh, R. C. Borghaei, R. D. Thornton and J. H. Bee, “Human Gingival Fibroblasts Produce Nitric Oxide in Response to Proinflammatory Cytokines,” Journal of Periodontology, Vol. 73, No. 4, 2002, pp. 392-400. doi:10.1902/jop.2002.73.4.392

[13]   B. R. Rifkin, A. T. Vernillo and L. M. Golub, “Blocking Periodontal Disease Progression By Inhibiting Tissue-Destructive Enzymes: A Potential Therapeutic Role for Tetracyclines and Their Chemically-Modified Analogs,” Journal of Periodontology, Vol. 64, No. 8, 1993, pp. 819-827. doi:10.1902/jop.1993.64.8s.819

[14]   P. Sangsanoh and P. Supaphol, “Stability Improvement of Electrospun Chitosan Nanofibrous Membranes in Neutral or Weak Basic Aqueous Solutions,” Biomacromolecules, Vol. 7, No. 10, 2006, pp. 2710-2714. doi:10.1021/bm060286l

[15]   C.-Y. Chang and S. Yamada, “Evaluation of the Regenerative Effect of a 25% Doxycycline-Loaded Biodegradable Membrane for Guided Tissue Regeneration,” Journal of Periodontology, Vol. 71, No. 7, 2000, pp. 1086-1093. doi:10.1902/jop.2000.71.7.1086

[16]   Y.-T. Chen, S.-L. Hung, L.-W. Lin, L.-Y. Chi and L.-J. Ling, “Attachment of Periodontal Ligament Cells to Chlor-hexidine-Loaded Guided Tissue Regeneration Membranes,” Journal of Periodontology, Vol. 74, No. 11, 2003, pp. 1652-1659. doi:10.1902/jop.2003.74.11.1652

[17]   Y. J. Park, Y. M. Lee, S. N. Park, J. Y. Lee, Y. Ku, C. P. Chung and S. J. Lee, “Enhanced Guided Bone Regeneration by Controlled Tetracycline Release from Poly(L- Lactide) Barrier Membranes,” Journal of Biomedical Materials Research, Vol. 51, No. 3, 2000, pp. 391-739. doi:10.1002/1097-4636(20000905)51:3<391::AID-JBM13>3.0.CO;2-9

[18]   M. Minabe, T. Kodama, T. Kogou, H. Fushimi, T. Sugiyama, K. Takeuchi, E. Miterai and S. Nishikubo, “Clinical Significance of Antibiotic Therapy in Guided Tissue Regeneration with a Resorbable Membrane,” Periodontal Clinical Investigations, Vol. 23, No. 1, 2001, pp. 20-30.

[19]   P. S. Bland, J. M. Goodson, J. C. Gunsolley, S. G. Grossi, J. Otomo-Corgel, F. Doherty and J. L. Comiskey, “Association of Antimicrobial and Clinical Efficacy: Periodontitis Therapy with Minocycline Microspheres,” Journal of the International Academy of Periodontology, Vol. 12, No. 1, 2010, pp. 11-19.

 
 
Top