Insights into Functional Tetracycline/Antioxidant Containing Chitosan Hydrogels as Potential Bio-Active Restorative Materials: Structure, Function and Antimicrobial Activity


The human inflammatory periodontal diseases are amongst the most common of chronic diseases to affect adults. Periodontitis is regarded as “an inflammatory lesion, mediated by complex host-parasite interactions, that leads to the loss of connective tissue attachment to root surface cementum and adjacent alveolar bone”. Substantial data are available in the literature on the role of reactive oxygen species (ROS) and antioxidants in disorders such as the inflammatory diseases. However, remarkably little information is available on the periodontal diseases, which show many of the pathological features of other chronic inflammatory diseases. The periodontal tissues also provide an ideal medium within which to study mechanisms of ROS mediated tissue damage and of antioxidant defense in response to bacterial colonisation, through the non-invasive collection of GCF. The objectives of this study are to evaluate the novel chitosan based functional drug delivery systems which can be successfully incorporated into “dual action bioactive restorative materials” containing common antibiotics such as tetracycline, krill oil, aloe and aspirin as commonly used antioxidant species. Methods: The novel hydrogels will be investigated with respect to the antioxidant capacity and drug release capacity of the tetracycline from the designer drug delivery system, the use of SEM imaging for the characterization of the surfaces and reactive features of novel materials with antimicrobial potential. Results: A steady slow release of tetracycline, while maintaining antibiotic effects against the tested bacteria, for at least 10 days was shown from designer chitosan-antioxidant hydrogels. Within the limitations of the study design chitosan-antioxidant hydrogels are suitable materials for functional restorative and periodontal applications in vitro. The addition of antioxidants to the tetracycline containing prototype delivery system had a beneficial effect on the design of the hydrogel by slowing down the release of tetracycline and thereby enabling a sustainable antifungal activity over time.

Share and Cite:

Perchyonok, V. , Zhang, S. , Basson, N. , Grobler, S. , Oberholzer, T. and Massey, W. (2014) Insights into Functional Tetracycline/Antioxidant Containing Chitosan Hydrogels as Potential Bio-Active Restorative Materials: Structure, Function and Antimicrobial Activity. Open Journal of Stomatology, 4, 99-108. doi: 10.4236/ojst.2014.43016.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Goodson, J.M., Haffajee, A. and Socransky, S.S. (1979) Periodontal Therapy by Local Delivery of Tetracycline. Journal of Clinical Periodontology, 6, 83-92.
[2] Goodson, J.M., Cugini, M.A., Kent, R.L., et al. (1991) Multicenter Evaluation of Tetracycline Fiber Therapy: I. Experimental Design, Methods, and Baseline Data. Journal of Periodontal Research, 26, 361-370.
[3] Goodson, J.M., Cugini, M.A., Kent, R.L., et al. (1991) Multicenter Evaluation of Tetracycline Fiber Therapy: II. Clinical Response. Journal of Periodontal Research, 26, 371-379.
[4] Newman, M.G., Kornman, K.S. and Doherty, F.M. (1994) A 6-Month Multi-Center Evaluation of Adjunctive Tetracycline Fiber Therapy Used in Conjunction with Scaling and Root Planning in Maintenance Patients: Clinical Results. Journal of Periodontology, 65, 685-691.
[5] Soskolne, W.A., Heasman, P.A., Stabholz, A., et al. (1997) Sustained Local Delivery of Chlorhexidine in the Treatment of Periodontitis: A Multi-Center Study. Journal of Periodontology, 68, 32-38.
[6] van Steenberghe, D., Bercy, P., Kohl, J., et al. (1993) Subgingival Minocycline Hydrochloride Ointment in Moderate to Severe Chronic Adult Periodontitis: A Randomized, Doubleblind, Vehicle-Controlled, Multicenter Study. Journal of Periodontology, 64, 637-644.
[7] Ainamo, J., Lie, T., Ellingsen, B.H., et al. (1992) Clinical Responses to Subgingival Application of a Metronidazole 25% Gel Compared to the Effect of Subgingival Scaling in Adult Periodontitis. Journal of Clinical Periodontology, 19, 723-729.
[8] Jeffcoat, M.K., Bray, K.S., Ciancio, S.G., et al. (1998) Adjunctive Use of a Subgingival Controlled Release Chlorhexidine Chip Reduces Probing Depth and Improves Attachment Level Compared with Scaling and Root Planning Alone. Journal of Periodontology, 69, 989-997.
[9] Garrett, S., Johnson, L., Drisko, C.H., et al. (1999) Two Multi-Center Studies Evaluating Locally Delivered Doxycycline Hyclate, Placebo Control, Oral Hygiene, and Scaling and Root Planing in the Treatment of Periodontitis. Journal of Periodontology, 70, 490-503.
[10] Tonetti, M., Cugini, M.A. and Goodson, J.M. (1990) Zero-Order Delivery with Periodontal Placement of Tetracycline-Loaded Ethylene Vinyl Acetate Fibers. Journal of Periodontal Research, 25, 243-249.
[11] Greenstein, G. (1987) Effects of Subgingival Irrigation on Periodontal Status. Journal of Periodontology, 58, 827-836.
[12] Rethman, M. and Greenstein, G. (1994) Oral Irrigation in the Treatment of Periodontal Diseases. Current Opinion in Periodontology, 99-110.
[13] Khor, E. and Lim, L.Y. (2003) Implantable Applications of Chitin and Chitosan. Biomaterials, 24, 2339-2349.
[14] Athanasiou, K.A., Shah, A.R., Hernandez, R.J. and LeBaron, R.G. (2001) Basic Science of Articular Cartilage Repair. Clinical Journal of Sport Medicine, 20, 223-247.
[15] Dornish, M., Kaplan, D. and Skaugrud, O. (2001) Standards and Guidelines for Biopolymers in Tissue-Engineered Medical Products: ASTM Alginate and Chitosan Standard Guides. American Society for Testing and Materials. Annals of the New York Academy of Sciences, 944, 388-397.
[16] Hu, Q., Li, B., Wang, M. and Shen, J. (2004) Preparation and Characterization of Biodegradable Chitosan/Hydroxyapatite Nanocomposite Rods via in Situ Hybridization: A Potential Material as Internal Fixation of Bone Fracture. Biomaterials, 25, 779-785.
[17] Risbud, M.V. and Bhonde, R.R. (2000) Polyacryla-midechitosan Hydrogels: In Vitro Biocompatibility and Sustained Antibiotic Release Studies. Drug Delivery, 7, 69-75.
[18] Chow, K.S. and Khor, E. (2000) Novel Fabrication of Open-Pore Chitin Matrixes. Biomacromolecules, 1, 61-67.
[19] Senel, S., Ikinci, G., Kas, S., Yousefi-Rad, A., Sargon, M.F. and Hincal, A.A. (2000) Chitosan Films and Hydrogels of Chlorhexidine Gluconate for Oral Mucosal Delivery. International Journal of Pharmaceutics, 193, 197-203.
[20] Needleman, I.G., Smales, F.C. and Martin, G.P. (1997) An Investigation of Bioadhesion for Periodontal and Oral Mucosal Drug Delivery. Journal of Clinical Periodontology, 24, 394-400.
[21] Lin, D.M., Kalachandra, S., Valiyaparambil, J. and Offenbacher, S. (2003) A Polymeric Device for Delivery of Anti-Microbial and Anti-Fungal Drugs in the Oral Environment: Effect of Temperature and Medium on the Rate of Drug Release. Dental Materials, 19, 589-596.
[22] Mi, F.L., Shyu, S.S., Chen, C.T. and Schoung, J.Y. (1999) Porous Chitosan Microsphere for Controlling the Antigen Release of Newcastle Disease Vaccine: Preparation of Antigen Adsorbed Microsphere and in Vitro Release. Biomaterials, 20, 1603-1612.
[23] Park, Y.J., Lee, J.Y., Yeom, H.R., et al. (2005) Injectable Polysaccharide Microcapsules for Prolonged Release of Minocycline for the Treatment of Periodontitis. Biotechnology Letters, 27, 1761-1766.
[24] Chung, T.W., Lu, Y.F., Wang, S.S., Lin, Y.S. and Chu, S.H. (2002) Growth of Human Endothelial Cells on Photochemically Grafted Gly-Arg-Gly-Asp (GRGD) Chitosans. Biomaterials, 23, 4803-4809.
[25] Flemmig, T.F., Weinacht, S., Rudiger, S., Rumetsch, M., Jung, A. and Klaiber, B. (1996) Adjunctive Controlled Topical Application of Tetracycline HCl in the Treatment of Localized Persistent or Recurrent Periodontitis. Effects on Clinical Parameters and Elastasealpha1-Proteinase Inhibitor in Gingival Crevicular Fluid. Journal of Clinical Periodontology, 23, 914-921.
[26] Odim, J., Laks, H., Allada, V., Child, J., Wilson, S. and Gjertson, D. (2005) Results of Aortic Valvesparing and Restoration with Autologous Pericardial Leaflet Extensions in Congenital Heart Disease. Annals of Thoracic Surgery, 80, 647-653.
[27] Myken, P.S. (2005) Seventeen-Year Experience with the St Jude Medical Biocor Porcine Bioprosthesis. Journal of Heart Valve Disease, 14, 486-492.
[28] Lu, H.K., Lee, S.Y. and Lin, F.P. (1998) Elastic Modulus, Permeation Time and Swelling Ratio of a New Porcine Dermal Collagen Membrane. Journal of Periodontal Research, 33, 243-248.
[29] Ishihara, M., Ono, K., Sato, M., et al. (2001) Acceleration of Wound Contraction and Healing with a Photocrosslinkable Chitosan Hydrogel. Wound Repair and Regeneration, 9, 513-521.
[30] Guo, J.F., Jourdian, G.W. and Mac-Callum, D.K. (1989) Culture and Growth Characteristics of Chondrocytes Encapsulated in Alginate Beads. Connective Tissue Research, 19, 277-297.
[31] Kawase, M., Michibayashi, N., Nakashima, Y., Kurikawa, N., Yagi, K. and Mizoguchi, T. (1997) Application of Glutaraldehyde-Crosslinked Chitosan as a Scaffold for Hepatocyte Attachment. Biological & Pharmaceutical Bulletin, 20, 708-710.
[32] Koyano, T., Minoura, N., Nagura, M. and Kobayashi, K. (1998) Attachment and Growth of Cultured Fibroblast Cells on PVA/Chitosan Blended Hydrogels. Journal of Biomedical Materials Research, 39, 486-490.<486::AID-JBM20>3.0.CO;2-7
[33] Lee, Y.M., Park, Y.J., Lee, S.J., et al. (2000) Tissue Engineered Bone Formation Using Chitosan/Tricalcium Phosphate Sponges. Journal of Periodontology, 71, 410-417.
[34] Zhang, Y. and Zhang, M. (2002) Three-Dimensional Macroporous Calcium Phosphate Bioceramics with Nested Chitosan Sponges for Load-Bearing Bone Implants. Journal of Biomedical Materials Research, 61, 1-8.
[35] Zhao, F., Yin, Y., Lu, W.W., et al. (2002) Preparation and Histological Evaluation of Biomimetic Three-Dimensional Hydroxyapatite/Chitosan-Gelatin Network Composite Scaffolds. Biomaterials, 23, 3227-3234.
[36] Anitua, E. (1999) Plasma Rich in Growth Factors: Preliminary Results of Use in the Preparation of Future Sites for Implants. International Journal of Oral & Maxillofacial Implants, 14, 529-535.
[37] Klokkevold, P.R., Vandemark, L., Kenney, E.B. and Bernard, G.W. (1996) Osteogenesis Enhanced by Chitosan (Poly-N-Acetyl Glucosaminoglycan) in Vitro. Journal of Periodontology, 67, 1170-1175.
[38] Mizuno, K., Yamamura, K., Yano, K., et al. (2003) Effect of Chitosan Film Containing Basic Fibroblast Growth Factor on Wound Healing in Genetically Diabetic Mice. Journal of Biomedical Materials Research, 64A, 177-181.
[39] Park, J.S., Choi, S.H., Moon, I.S., Cho, K.S., Chai, J.K. and Kim, C.K. (200) Eight-Week Histological Analysis on the Effect of Chitosan on Surgically Created One-Wall Intrabony Defects in Beagle Dogs. Journal of Clinical Periodontology, 30, 443-453.
[40] Chou, T.C., Fu, E. and Shen, E.C. (2003) Chitosan Inhibits Prostaglandin E2 Formation and Cyclooxygenase-2 Induction in Lipopolysaccharide-Treated RAW 264.7 Macrophages. Biochemical and Biophysical Research Communications, 308, 403-407.
[41] Bauer, A.W., Kirby, W.M.M., Sherris, J.C. and Turck, M. (1966) Antibiotic Susceptibility Testing by a Standardized Single Disc Method. American Journal of Clinical Pathology, 36, 493-496.

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.