Evaluation Of Antimicrobial and Cytotoxic Properties of Chondroitin Sulphate Based Hydrogel Incorporated with Dihydroxyacetone Phosphate, Copper Nanoparticles and Quercetin
Keywords:
Antioxidant, Chondroitin sulphate, Copper nanoparticles, Injectable hydrogelsAbstract
Introduction: Chondroitin sulfate, a natural component found in connective tissues and cartilage, possesses intrinsic antioxidant capabilities. These properties stem from its capacity to counteract free radicals, inhibit the activities of reactive oxygen species (ROS), and reduce oxidative stress within the local environment. The aim of the study is to evaluate the antimicrobial and cytotoxic properties of chondroitin sulphate based hydrogel incorporated with dihydroxyacetone phosphate, copper nanoparticles and quercetin.
Materials and methods: 10% chondroitin sulphate was methacrylated using methacrylic acid, and then supplemented with Cu nanoparticles and dihydroxyacetone phosphate/quercetin. The resulting solution was photocrosslinked using the photoinitiator I2959 to form a gel, which was subsequently freeze-dried. The lyophilized material was analyzed for swelling and degradation properties, tested for antimicrobial effects, and evaluated for cell compatibility using the MTT assay.
RESULTS: The culture plates show clear zones of inhibition around the hydrogel sample, indicating moderate antibacterial activity. This suggests that the Cu nanoparticles and quercetin incorporated in the formulation may effectively reduce bacterial growth, which is beneficial for applications in wound healing and implantable biomaterials.The control sample showed a viability of 91.2%, while the test sample recorded a slightly higher value of 93.6%. These characteristics are desirable in injectable hydrogels, as they improve adaptability to tissue architecture and enable better control over the material’s resorption and drug release.
CONCLUSION: In conclusion, the incorporation of Cu and DAP nanoparticles, along with quercetin, into CS- based injectable hydrogels holds great potential for the development of advanced biomaterials with enhanced antimicrobial and cytotoxic properties
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Kishen A, Cecil A, Chitra S. Fabrication of hydroxyapatite reinforced polymeric hydrogel membrane for regeneration. Saudi Dent J. 2023 Sep;35(6):678-683. doi: 10.1016/j.sdentj.2023.05.021.
G S, P T P, Cecil A, S C, Suresh N. Formulation of a Novel Polymeric Hydrogel Membrane for Periodontal Tissue Regeneration Using Tricalcium Phosphate-Alginate Reinforcement. Cureus. 2024 Apr 8;16(4):e57844. doi: 10.7759/cureus.57844.
Catoira MC, Fusaro L, Di Francesco D, Ramella M, Boccafoschi F. Overview of natural hydrogels for regenerative medicine applications. J Mater Sci Mater Med [Internet]. 2019 Oct 10;30(10):115. Available from: http://dx.doi.org/10.1007/s10856-019-6318-7
Yuan FZ, Wang HF, Guan J, Fu JN, Yang M, Zhang JY, et al. Fabrication of Injectable Chitosan-Chondroitin Sulfate Hydrogel Embedding Kartogenin-Loaded Microspheres as an Ultrasound-Triggered Drug Delivery System for Cartilage Tissue Engineering. Pharmaceutics [Internet]. 2021 Sep 16;13(9). Available from: http://dx.doi.org/10.3390/pharmaceutics13091487
Shah SA, Sohail M, Khan SA, Kousar M. Improved drug delivery and accelerated diabetic wound healing by chondroitin sulfate grafted alginate-based thermoreversible hydrogels. Mater Sci Eng C Mater Biol Appl [Internet]. 2021 Jul;126:112169. Available from: http://dx.doi.org/10.1016/j.msec.2021.112169
Jabeen N, Sohail M, Shah SA, Mahmood A, Khan S, Kashif MUR, et al. Silymarin nanocrystals-laden chondroitin sulphate-based thermoreversible hydrogels; A promising approach for bioavailability enhancement. Int J Biol Macromol [Internet]. 2022 Oct 1;218:456–72. Available from: http://dx.doi.org/10.1016/j.ijbiomac.2022.07.114
He Y, Sun M, Wang J, Yang X, Lin C, Ge L, et al. Chondroitin sulfate microspheres anchored with drug-loaded liposomes play a dual antioxidant role in the treatment of osteoarthritis. Acta Biomater [Internet]. 2022 Oct 1;151:512–27. Available from: http://dx.doi.org/10.1016/j.actbio.2022.07.052
Zhang Y, Chen W, Feng W, Fang W, Han X, Cheng C. Multifunctional chondroitin sulfate based hydrogels for promoting infected diabetic wounds healing by chemo-photothermal antibacterial and cytokine modulation. Carbohydr Polym [Internet]. 2023 Aug 15;314:120937. Available from: http://dx.doi.org/10.1016/j.carbpol.2023.120937
Sahiner M, Suner SS, Yilmaz AS, Sahiner N. Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability. Polymers [Internet]. 2022 Oct 14;14(20). Available from: http://dx.doi.org/10.3390/polym14204324
Milinčić DD, Popović DA, Lević SM, Kostić AŽ, Tešić ŽL, Nedović VA, et al. Application of Polyphenol-Loaded Nanoparticles in Food Industry. Nanomaterials (Basel) [Internet]. 2019 Nov 16;9(11). Available from: http://dx.doi.org/10.3390/nano9111629
AbdElrazek DA, Ibrahim MA, Hassan NH, Hassanen EI, Farroh KY, Abass HI. Neuroprotective effect of quercetin and nano-quercetin against cyclophosphamide-induced oxidative stress in the rat brain: Role of Nrf2/ HO-1/Keap-1 signaling pathway. Neurotoxicology [Internet]. 2023 Sep;98:16–28. Available from: http://dx.doi.org/10.1016/j.neuro.2023.06.008
Li X, Xu Q, Johnson M, Wang X, Lyu J, Li Y, et al. A chondroitin sulfate based injectable hydrogel for delivery of stem cells in cartilage regeneration. Biomater Sci [Internet]. 2021 Jun 4;9(11):4139–48. Available from: http://dx.doi.org/10.1039/d1bm00482d
Chen F, Yu S, Liu B, Ni Y, Yu C, Su Y, et al. An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering. Sci Rep [Internet]. 2016 Jan 28;6:20014. Available from: http://dx.doi.org/10.1038/srep20014
Ganesh SB, Aravindan M, Kaarthikeyan G, Martin TM, Kumar MS, Chitra S. Embryonic toxicology evaluation of novel Cissus quadrangularis, bioceramics and tendon extracellular matrix incorporated scaffolds for periodontal bone regeneration using zebrafish model. Journal of Oral Biology and Craniofacial Research. 2025 May 1;15(3):563-9.
Ben Jaballah M, Ambily Rajendran A, Prieto-Simón B, Dridi C. Development of a sustainable nanosensor using green Cu nanoparticles for simultaneous determination of antibiotics in drinking water. Anal Methods [Internet]. 2022 May 27;14(20):2014–25. Available from: http://dx.doi.org/10.1039/d2ay00419d
Jessop IA, Pérez YP, Jachura A, Nuñez H, Saldías C, Isaacs M, et al. New Hybrid Copper Nanoparticles/Conjugated Polyelectrolyte Composite with Antibacterial Activity. Polymers [Internet]. 2021 Jan 27;13(3). Available from: http://dx.doi.org/10.3390/polym13030401
Khokhar D, Jadoun S, Arif R, Jabin S, Rathore DS. Facile synthesis of the chemically oxidative grafted copolymer of 2,6-diaminopyridine (DAP) and thiophene (Th) for optoelectronic and antioxidant studies. J Mol Struct [Internet]. 2022 Jan 15;1248:131453. Available from: https://www.sciencedirect.com/science/article/pii/S0022286021015817
Vieira IRS, de Carvalho APA de, Conte-Junior CA. Recent advances in biobased and biodegradable polymer nanocomposites, nanoparticles, and natural antioxidants for antibacterial and antioxidant food packaging applications. Compr Rev Food Sci Food Saf [Internet]. 2022 Jul;21(4):3673–716. Available from: http://dx.doi.org/10.1111/1541-4337.12990
Hassanen EI, Tohamy AF, Issa MY, Ibrahim MA, Farroh KY, Hassan AM. Pomegranate Juice Diminishes The Mitochondria-Dependent Cell Death And NF-kB Signaling Pathway Induced By Copper Oxide Nanoparticles On Liver And Kidneys Of Rats. Int J Nanomedicine [Internet]. 2019 Nov 15;14:8905–22. Available from: http://dx.doi.org/10.2147/IJN.S229461
Tao BB, Wu NN, Zhang HD, Wang HB. Blocking the Cu (II) Ions Mediated Catalytical Ability for Construction of Ratiometric Fluorescence Sensing Platform Based on Glutathione-Stabilized Copper Nanoclusters. J Electrochem Soc [Internet]. 2022 Mar 30 [cited 2023 Nov 18];169(3):037529. Available from: https://iopscience.iop.org/article/10.1149/1945-7111/ac5f1e/meta
Hanurry EY, Birhan YS, Darge HF, Mekonnen TW, Arunagiri V, Chou HY, et al. PAMAM Dendritic Nanoparticle-Incorporated Hydrogel to Enhance the Immunogenic Cell Death and Immune Response of Immunochemotherapy. ACS Biomater Sci Eng [Internet]. 2022 Jun 13;8(6):2403–18. Available from: http://dx.doi.org/10.1021/acsbiomaterials.2c00171
Muzzarelli RAA, Greco F, Busilacchi A, Sollazzo V, Gigante A. Chitosan, hyaluronan and chondroitin sulfate in tissue engineering for cartilage regeneration: a review. Carbohydr Polym [Internet]. 2012 Jul 1;89(3):723–39. Available from: http://dx.doi.org/10.1016/j.carbpol.2012.04.057
Park H, Choi B, Hu J, Lee M. Injectable chitosan hyaluronic acid hydrogels for cartilage tissue engineering. Acta Biomater [Internet]. 2013 Jan;9(1):4779–86. Available from: http://dx.doi.org/10.1016/j.actbio.2012.08.033
Kaya S, Yesudass S, Arthanari S, Bose S, Serdaroğlu G. Materials Development and Processing for Biomedical Applications [Internet]. CRC Press; 2022. 340 p. Available from: https://play.google.com/store/books/details?id=18pkEAAAQBAJ
González-Paredes A, Clarés-Naveros B, Ruiz-Martínez MA, Durbán-Fornieles JJ, Ramos-Cormenzana A, Monteoliva-Sánchez M. Delivery systems for natural antioxidant compounds: Archaeosomes and archaeosomal hydrogels characterization and release study. Int J Pharm [Internet]. 2011 Dec 15;421(2):321–31. Available from: http://dx.doi.org/10.1016/j.ijpharm.2011.09.042
Kumar M, Kumar D, Garg Y, Mahmood S, Chopra S, Bhatia A. Marine-derived polysaccharides and their therapeutic potential in wound healing application - A review. Int J Biol Macromol [Internet]. 2023 Oct 10;253(Pt 6):127331. Available from: http://dx.doi.org/10.1016/j.ijbiomac.2023.127331
Gnanasagar WR. Calcium Strontium Silicate-infused Alginate/Extracellular Matrix-based Scaffold for Periodontal Regeneration: An In Vitro Study. Dent. 2025;16(2):160-6.
Saha R, Patkar S, Pillai MM, Tayalia P. Bilayered skin substitute incorporating rutin nanoparticles for antioxidant, anti-inflammatory, and anti-fibrotic effect. Biomater Adv [Internet]. 2023 Jul;150:213432. Available from: http://dx.doi.org/10.1016/j.bioadv.2023.213432
Granados A, Pleixats R, Vallribera A. Recent Advances on Antimicrobial and Anti-Inflammatory Cotton Fabrics Containing Nanostructures. Molecules [Internet]. 2021 May 18;26(10). Available from: http://dx.doi.org/10.3390/molecules26103008
Pisoschi AM, Iordache F, Stanca L, Gajaila I, Ghimpeteanu OM, Geicu OI, et al. Antioxidant, Anti-inflammatory, and Immunomodulatory Roles of Nonvitamin Antioxidants in Anti-SARS-CoV-2 Therapy. J Med Chem [Internet]. 2022 Oct 13;65(19):12562–93. Available from: http://dx.doi.org/10.1021/acs.jmedchem.2c01134
Sapudom J, Kongsema M, Methachittipan A, Damrongsakkul S, Kanokpanont S, Teo JCM, et al. Degradation products of crosslinked silk fibroin scaffolds modulate the immune response but not cell toxicity. J Mater Chem B Mater Biol Med [Internet]. 2023 Apr 26;11(16):3607–16. Available from: http://dx.doi.org/10.1039/d3tb00097d
Bajpai D, Ramamurthy J. Role of alginate-based scaffolds for periodontal regeneration of intrabony defects: A systematic review. World Journal of Dentistry. 2024 Apr 2;15(2):181-7.
van Essen TH, van Zijl L, Possemiers T, Mulder AA, Zwart SJ, Chou CH, et al. Biocompatibility of a fish scale-derived artificial cornea: Cytotoxicity, cellular adhesion and phenotype, and in vivo immunogenicity. Biomaterials [Internet]. 2016 Mar;81:36–45. Available from: http://dx.doi.org/10.1016/j.biomaterials.2015.11.015
Das R, Suryawanshi N, Burnase N, Barapatre A, Dharshini RS, Kumar B, Kumar PS. Classification and bibliometric analysis of hydrogels in periodontitis treatment: Trends, mechanisms, advantages, and future research directions. Dental Materials. 2024 Nov 6.
Huynh V, Wylie RG. Competitive Affinity Release for Long-Term Delivery of Antibodies from Hydrogels. Angew Chem Int Ed Engl [Internet]. 2018 Mar 19;57(13):3406–10. Available from: http://dx.doi.org/10.1002/anie.201713428
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