2509001243
  • Open Access
  • Article

Substrate-Independent Antibacterial Coatings with Optimal Concentration of Covalently Immobilised Silver Nanoparticles That Support Osteogenesis

  • Neethu Ninan 1, 2,   
  • Fei Wei 3,   
  • Dennis Palms 1,   
  • Peter Zilm 4,   
  • Yunpeng Zhao 5,   
  • Richard Bright 1, *,   
  • Yin Xiao 3, 6, 7,   
  • Krasimir Vasilev 1, *

Received: 12 Aug 2025 | Revised: 02 Sep 2025 | Accepted: 04 Sep 2025 | Published: 10 Sep 2025

Abstract

Medical device-associated infections remain a major clinical challenge, frequently leading to implant failure, patient morbidity and mortality, and high healthcare costs. Equally critical is effective device osteointegration, which is often compromised in environments prone to infection. Here, we present a multifunctional, substrate-independent surface coating that simultaneously imparts robust antibacterial activity and promotes osteogenesis through modulation of inflammation. A thin plasma polymer layer derived from 2-methyl-2-oxazoline was deposited on material substrates to facilitate covalent binding of controlled concentrations of silver nanoparticles (AgNPs), functionalized with 2-mercaptosuccinic acid using oxazoline ring-opening chemistry. The coatings exhibited potent antibacterial effects against both Gram-positive and Gram-negative pathogens, including Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, while maintaining cytocompatibility with human cells. Mechanistic studies revealed that the AgNPs functionalized surfaces exhibited a concentration-dependent modulation of inflammatory cytokine and osteoclastogenic markers expression in macrophages, while promoting osteogenic signalling in co-cultured human bone marrow stromal cells. Coatings having immobilized AgNP at a concentration of 9 At% achieved an optimal balance between antibacterial efficacy and osteoimmunomodulation. This study demonstrates that finely tuning the AgNPs surface concentration can deliver a bioactive coating platform with dual antibacterial and osteogenic functionality, offering promising translational potential for a wide range of medical implants where osteointegration is vital, such as in orthopaedics and dentistry.

References 

  • 1.
    Darouiche, R.O. Treatment of infections associated with surgical implants. N. Engl. J. Med. 2004, 350, 1422–1429.
  • 2.
    Rosenthal, V.D.; Al-Abdely, H.M.; El-Kholy, A.A.; et al. International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module. Am. J. Infect. Control 2016, 44, 1495–1504.
  • 3.
    Vasilev, K.; Poulter, N.; Martinek, P.; et al. Controlled Release of Levofloxacin Sandwiched between Two Plasma Polymerized Layers on a Solid Carrier. ACS Appl. Mater. Interfaces 2011, 3, 4831–4836.
  • 4.
    Dudeck, M.A.; Edwards, J.R.; Allen-Bridson, K.; et al. National Healthcare Safety Network report, data summary for 2013, Device-associated Module. Am. J. Infect. Control 2015, 43, 206–221.
  • 5.
    Li, B.; Thebault, P.; Labat, B.; et al. Implants coating strategies for antibacterial treatment in fracture and defect models: A systematic review of animal studies. J. Orthop. Transl. 2024, 45, 24–35.
  • 6.
    Zimlichman, E.; Henderson, D.; Tamir, O.; et al. Health Care–Associated Infections: A Meta-analysis of Costs and Financial Impact on the US Health Care System. JAMA Intern. Med. 2013, 173, 2039–2046.
  • 7.
    Bleyer, A.J. Use of antimicrobial catheter lock solutions to prevent catheter-related bacteremia. Clin. J. Am. Soc. Nephrol. CJASN 2007, 2, 1073–1078.
  • 8.
    Allegranzi, B.; Bagheri Nejad, S.; Combescure, C.; et al. Burden of endemic health-care-associated infection in developing countries: Systematic review and meta-analysis. Lancet 2011, 377, 228–241.
  • 9.
    Deen, J.; von Seidlein, L.; Andersen, F.; et al. Community-acquired bacterial bloodstream infections in developing countries in south and southeast Asia: A systematic review. Lancet. Infect. Dis. 2012, 12, 480–487.
  • 10.
    Bagheri Nejad, S.; Allegranzi, B.; Syed, S.B.; et al. Health-care-associated infection in Africa: A systematic review. Bull. World Health Organ. 2011, 89, 757–765.
  • 11.
    Grayson, M.L. Kucers' the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic and Antiviral Drugs; CRC Press: Boca Raton, FL, USA, 2017.
  • 12.
    Diab-El Schahawi, M.; Presterl, E.; Reilly, J.S. Basic Microbiology and Infection Control for Midwives, 1st ed.; Springer International Publishing: Cham, Switzerland, 2019.
  • 13.
    Bright, R.; Hayles, A.; Wood, J.; et al. Surfaces Containing Sharp Nanostructures Enhance Antibiotic Efficacy. Nano Lett. 2022, 22, 6724–6731.
  • 14.
    Shree, P.; Singh, C.K.; Sodhi, K.K.; et al. Biofilms: Understanding the structure and contribution towards bacterial resistance in antibiotics. Med. Microecol. 2023, 16, 100084.
  • 15.
    Lim, L.M.; Ly, N.; Anderson, D.; et al. Resurgence of colistin: A review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy 2010, 30, 1279–1291.
  • 16.
    Robles, M.; Toscano, E.; Cotta, J.; et al. Antibiotic-induced liver toxicity: Mechanisms, clinical features and causality assessment. Curr. Drug Saf. 2010, 5, 212–222.
  • 17.
    Montanari, E.; Bernardo, G.; Le Noci, V.; et al. Biofilm formation by the host microbiota: A protective shield against immunity and its implication in cancer. Mol Cancer 2025, 24, 148.
  • 18.
    Mihai, M.M.; Holban, A.M.; Giurcaneanu, C.; et al. Microbial biofilms: Impact on the pathogenesis of periodontitis, cystic fibrosis, chronic wounds and medical device-related infections. Curr. Top. Med. Chem. 2015, 15, 1552–1576.
  • 19.
    Martínez, J.L. Antibiotics and antibiotic resistance genes in natural environments. Science 2008, 321, 365–367.
  • 20.
    Vasilev, K.; Cook, J.; Griesser, H.J. Antibacterial surfaces for biomedical devices. Expert Rev. Med. Devices 2009, 6, 553–567.
  • 21.
    Vasilev, K.; Griesser, S.S.; Griesser, H.J. Antibacterial Surfaces and Coatings Produced by Plasma Techniques. Plasma Process. Polym. 2011, 8, 1010–1023.
  • 22.
    Hasan, J.; Bright, R.; Hayles, A.; et al. Preventing Peri-implantitis: The Quest for a Next Generation of Titanium Dental Implants. ACS Biomater. Sci. Eng. 2022, 8, 4697–4737.
  • 23.
    Bright, R.; Hayles, A.; Wood, J.; et al. Interplay between Immune and Bacterial Cells on a Biomimetic Nanostructured Surface: A “Race for the Surface” Study. ACS Appl. Bio Mater. 2023, 6, 3472–3483.
  • 24.
    Romo-Rico, J.; Bright, R.; Krishna, S.M.; et al. Antimicrobial graphene-based coatings for biomedical implant applications. Carbon Trends 2023, 12, 100282.
  • 25.
    Chernousova, S.; Epple, M. Silver as Antibacterial Agent: Ion, Nanoparticle, and Metal. Angew. Chem. Int. Ed. 2013, 52, 1636–1653.
  • 26.
    Taheri, S.; Baier, G.; Majewski, P.; et al. Synthesis and antibacterial properties of a hybrid of silver–potato starch nanocapsules by miniemulsion/polyaddition polymerization. J. Mater. Chem. B 2014, 2, 1838–1845.
  • 27.
    Alexander, J.W. History of the medical use of silver. Surg. Infect. 2009, 10, 289–292.
  • 28.
    Beattie, M.; Taylor, J. Silver alloy vs. uncoated urinary catheters: A systematic review of the literature. J. Clin. Nurs. 2011, 20, 2098–2108.
  • 29.
    Jiang, Y.; Zhang, Q.; Wang, H.; et al. Effectiveness of silver and iodine dressings on wound healing: A systematic review and meta-analysis. BMJ Open 2024, 14, e077902.
  • 30.
    Liang, K.; Liu, Y.; Jiang, F. Analysis of therapeutic effect of silver-based dressings on chronic wound healing. Int. Wound J. 2024, 21, e70006.
  • 31.
    Macgregor-Ramiasa, M.N.; Cavallaro, A.A.; Vasilev, K. Properties and reactivity of polyoxazoline plasma polymer films. J. Mater. Chem. B 2015, 3, 6327–6337.
  • 32.
    Ramiasa, M.N.; Cavallaro, A.A.; Mierczynska, A.; et al. Plasma polymerised polyoxazoline thin films for biomedical applications. Chem. Commun. 2015, 51, 4279–4282.
  • 33.
    Cavallaro, A.A.; Macgregor-Ramiasa, M.N.; Vasilev, K. Antibiofouling Properties of Plasma-Deposited Oxazoline-Based Thin Films. ACS Appl. Mater. Interfaces 2016, 8, 6354–6362.
  • 34.
    Ninan, N.; Joseph, B.; Visalakshan, R.M.; et al. Plasma assisted design of biocompatible 3D printed PCL/silver nanoparticle scaffolds: In vitro and in vivo analyses. Mater. Adv. 2021, 2, 6620–6630.
  • 35.
    Goreham, R.V.; Short, R.D.; Vasilev, K. Method for the Generation of Surface-Bound Nanoparticle Density Gradients. J. Phys. Chem. C 2011, 115, 3429–3433.
  • 36.
    Hernandez-Lopez, J.L.; Bauer, R.E.; Chang, W.S.; et al. Functional polymers as nanoscopic building blocks. Mater. Sci. Eng. C 2003, 23, 267–274.
  • 37.
    Macgregor-Ramiasa, M.; McNicholas, K.; Ostrikov, K.; et al. A platform for selective immuno-capture of cancer cells from urine. Biosens. Bioelectron. 2017, 96, 373–380.
  • 38.
    Alemie, M.N.; Bright, R.; Nguyen, N.H.; et al. Surface Chemistry Induced IgG Unfolding and Modulation of Immune Responses. ACS Appl. Mater. Interfaces 2024, 16, 50507–50523.
  • 39.
    Vasilev, K.; Sah, V.; Anselme, K.; et al. Tunable antibacterial coatings that support mammalian cell growth. Nano Lett 2010, 10, 202–207.
  • 40.
    Nguyen, T.T.; Zhang, P.; Bi, J.; et al. Silver─Gallium Nano-Amalgamated Particles as a Novel, Biocompatible Solution for Antibacterial Coatings. Adv. Funct. Mater. 2024, 34, 2310539.
  • 41.
    Haidari, H.; Kopecki, Z.; Bright, R.; et al. Ultrasmall AgNP-Impregnated Biocompatible Hydrogel with Highly Effective Biofilm Elimination Properties. ACS Appl. Mater. Interfaces 2020, 12, 41011–41025.
  • 42.
    Vasilev, K.; Michelmore, A.; Martinek, P.; et al. Early Stages of Growth of Plasma Polymer Coatings Deposited from Nitrogen- and Oxygen-Containing Monomers. Plasma Process. Polym. 2010, 7, 824–835.
  • 43.
    Taheri, S.; Cavallaro, A.; Christo, S.N.; et al. Substrate independent silver nanoparticle based antibacterial coatings. Biomaterials 2014, 35, 4601–4609.
  • 44.
    Berger, A.; Edelsberg, J.; Oster, G.; et al. Patterns of Initial Antibiotic Therapy for Complicated Skin and Skin Structure Infections (cSSSI) in US Hospitals, 2000–2009. Infect. Dis. Clin. Pract. 2013, 21, 159–167.
  • 45.
    O’Gara, J.P.; Humphreys, H. Staphylococcus epidermidis biofilms: Importance and implications. J. Med. Microbiol. 2001, 50, 582–587.
  • 46.
    Otto, M. Staphylococcal Biofilms. Microbiol. Spectr. 2018, 6. https://doi.org/10.1128/microbiolspec.GPP3-0023-2018.
  • 47.
    Pavlovsky, L.; Sturtevant, R.A.; Younger, J.G.; et al. Effects of temperature on the morphological, polymeric, and mechanical properties of Staphylococcus epidermidis bacterial biofilms. Langmuir ACS J. Surf. Colloids 2015, 31, 2036–2042.
  • 48.
    Walker, J.T.; Jhutty, A.; Parks, S.; et al. Investigation of healthcare-acquired infections associated with Pseudomonas aeruginosa biofilms in taps in neonatal units in Northern Ireland. J. Hosp. Infect. 2014, 86, 16–23.
  • 49.
    Le Feuvre, R.A.; Brough, D.; Iwakura, Y.; et al. Priming of Macrophages with Lipopolysaccharide Potentiates P2X7-mediated Cell Death via a Caspase-1-dependent Mechanism, Independently of Cytokine Production. J. Biol. Chem. 2002, 277, 3210–3218.
  • 50.
    Park, B.S.; Lee, J.-O. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp. Mol. Med. 2013, 45, e66.
  • 51.
    Mareddy, S.; Crawford, R.; Brooke, G.; et al. Clonal isolation and characterization of bone marrow stromal cells from patients with osteoarthritis. Tissue Eng. 2007, 13, 819–829.
  • 52.
    Singh, S.; Jones, B.J.; Crawford, R.; et al. Characterization of a mesenchymal-like stem cell population from osteophyte tissue. Stem Cells Dev. 2008, 17, 245–254.
  • 53.
    Chen, Z.; Klein, T.; Murray, R.Z.; et al. Osteoimmunomodulation for the development of advanced bone biomaterials. Mater. Today 2016, 19, 304–321.
  • 54.
    He, W.; Elkhooly, T.A.; Liu, X.; et al. Silver nanoparticle based coatings enhance adipogenesis compared to osteogenesis in human mesenchymal stem cells through oxidative stress. J. Mater. Chem. B 2016, 4, 1466–1479.
  • 55.
    Xiu, Z.; Zhang, Q.; Puppala, H.L.; et al. Negligible Particle-Specific Antibacterial Activity of Silver Nanoparticles. Nano Lett. 2012, 12, 4271–4275.
  • 56.
    Liu, J.; Hurt, R.H. Ion Release Kinetics and Particle Persistence in Aqueous Nano-Silver Colloids. Environ. Sci. Technol. 2010, 44, 2169–2175.
  • 57.
    Dreikausen, L.; Blender, B.; Trifunovic-Koenig, M.; et al. Analysis of microbial contamination during use and reprocessing of surgical instruments and sterile packaging systems. PLoS ONE 2023, 18, e0280595.
  • 58.
    Wang, S.; van Dijl, J.M. Disinfection of medical devices with a steam machine that operates at atmospheric pressure and is suitable for home usage. Sci. Rep. 2025, 15, 25486.
  • 59.
    Yang, H.; Wang, Y.; Yao, L.; et al. Antifouling Polymer Coatings for Bioactive Surfaces. Langmuir : ACS J. Surf. Colloids 2025, 41, 6471–6496.
  • 60.
    Wang, A.; Pu, K.; Dong, B.; et al. Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells. J. Appl. Toxicol. JAT 2013, 33, 1156–1164.
  • 61.
    Werner, S.; Krieg, T.; Smola, H. Keratinocyte-fibroblast interactions in wound healing. J. Investig. Dermatol. 2007, 127, 998–1008.
  • 62.
    Yang, A.; Cardona, D.L.; Barile, F.A. In vitro cytotoxicity testing with fluorescence-based assays in cultured human lung and dermal cells. Cell Biol. Toxicol. 2002, 18, 97–108.
  • 63.
    Ninan, N.; Muthiah, M.; Park, I.-K.; et al. Faujasites Incorporated Tissue Engineering Scaffolds for Wound Healing: In Vitro and In Vivo Analysis. ACS Appl. Mater. Interfaces 2013, 5, 11194–11206.
  • 64.
    Wiegand, C.; Hipler, U.C. Evaluation of biocompatibility and cytotoxicity using keratinocyte and fibroblast cultures. Ski. Pharmacol Physiol 2009, 22, 74–82.
  • 65.
    Mayol, L.; De Stefano, D.; De Falco, F.; et al. Effect of hyaluronic acid on the thermogelation and biocompatibility of its blends with methyl cellulose. Carbohydr. Polym. 2014, 112, 480–485.
  • 66.
    Burrell, R.E. A scientific perspective on the use of topical silver preparations. Ostomy/Wound Manag. 2003, 49, 19–24.
  • 67.
    Nadworny, P.L.; Wang, J.; Tredget, E.E.; et al. Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model. Nanomed. Nanotechnol. Biol. Med. 2008, 4, 241–251.
  • 68.
    Warriner, R.; Burrell, R. Infection and the chronic wound: A focus on silver. Adv. Ski. Wound Care 2005, 18, 2–12.
  • 69.
    Xie, H.; Pei, W.; and Wu, J. Effect of exposure of osteoblast-like cells to low-dose silver nanoparticles: Uptake, retention and osteogenic activity. Artif. Cells Nanomed. Biotechnol. 2019, 47, 260–267.
  • 70.
    Xiao, K.; Liu, C.; Tu, Z.; et al. Activation of the NF-κB and MAPK Signaling Pathways Contributes to the Inflammatory Responses, but Not Cell Injury, in IPEC-1 Cells Challenged with Hydrogen Peroxide. Oxidative Med. Cell. Longevity 2020, 2020, 5803639.
  • 71.
    Chen, J.; Chen, X.; Xuan, Y.; et al. Surface functionalization-dependent inflammatory potential of polystyrene nanoplastics through the activation of MAPK/NF-κB signaling pathways in macrophage Raw 264.7. Ecotoxicol. Environ. Saf. 2023, 251, 114520.
  • 72.
    Arya, P.N.; Saranya, I.; Selvamurugan, N. Crosstalk between Wnt and bone morphogenetic protein signaling during osteogenic differentiation. World J Stem Cells 2024, 16, 102–113.
  • 73.
    Wang, L.; Ruan, M.; Bu, Q.; et al. Signaling Pathways Driving MSC Osteogenesis: Mechanisms, Regulation, and Translational Applications. Int. J. Mol. Sci. 2025, 26, 1311.
  • 74.
    Bright, R.; Visalakshan, R.M.; Simon, J.; et al. Manipulation of Serum Protein Adsorption by Nanoengineered Biomaterials Influences Subsequent Immune Responses. ACS Biomater. Sci. Eng. 2024, 10, 6230–6240.
  • 75.
    Sharifianjazi, F.; Sharifianjazi, M.; Irandoost, M.; et al. Advances in Zinc-Containing Bioactive Glasses: A Comprehensive Review. J Funct Biomater 2024, 15, 258.
  • 76.
    Elbasuney, S.; El-Sayyad, G.S.; Radwan, S.M.; et al. Antimicrobial, and Antibiofilm Activities of Silver Doped Hydroxyapatite: A Novel Bioceramic Material for Dental Filling. J. Inorg. Organomet. Polym. Mater. 2022, 32, 4559–4575.
  • 77.
    Marsico, M.; Azari, R.; Curcio, M.; et al. Enhancing the Antibacterial Properties of Chitosan Coatings: Ag@Chitosan and Chitosan from Insects. Coatings 2024, 14, 925.
Share this article:
How to Cite
Ninan, N.; Wei, F.; Palms, D.; Zilm, P.; Zhao, Y.; Bright, R.; Xiao, Y.; Vasilev, K. Substrate-Independent Antibacterial Coatings with Optimal Concentration of Covalently Immobilised Silver Nanoparticles That Support Osteogenesis. Regenerative Medicine and Dentistry 2025, 2 (3), 11. https://doi.org/10.53941/rmd.2025.100011.
RIS
BibTex
Copyright & License
article copyright Image
Copyright (c) 2025 by the authors.