IR and Visible Light-Activated Antimicrobial Properties and Biosafety Issues of New Polymeric Hybrid Hydrogels Containing Non-Stoichiometric Metal Oxides Nanoparticles

The emergence of multi-drug-resistant bacteria, or superbugs, is a global issue for prosthetic biomaterials since they could be colonized by antibiotic-resistant pathogens sustaining the spread of infections. New research aimed at developing biomaterials that could prevent or control bacterial colonization is the current effort in this area [1-10]. The current paper is coherent with what is set by the new Horizon Europe (Global Challenges and European Industrial Competitiveness) and Agenda 2030 (goal 3-Ensure healthy lives and promote wellbeing for all ages). In particular, the research investigates the optimal combination of the material, manufacturing process, and surface modification to give birth to a new generation of coating materials characterised by reduced post-surgical complications. The development of anti-bacterial surfaces is entirely related to these topics since a decrease in infections is beneficial not only for the patient but also for the health system, leading to minor costs of hospitalization and revision procedures. The most common method to produce ‘antimicrobial materials’ is adding an active agent, such as silver ions, quaternary ammonium salts, phenols, and antibiotics, to the polymer as an additive [4-6]. These additives (most of them are biocides capable of killing all living organisms) are slowly leached into the surrounding environment killing the microorganisms, and can only be effective when leached. However, there are biosafety concerns of the use of materials impregnated with a leaching antibacterial agent, including contamination of the environment and short durations of antimicrobial action due to rapid leaching at the beginning of use (the so-called “burst effect” that involves an initially too high concentration of the released agent). Several alternative approaches have been used to make non-leaching biocidal materials to overwhelm these problems [7- 14]. The development of nano-materials with biocidal and antiviral traits provided several benefits to counter the surface and airborne contamination [4-6,15-20]. The already commonly used inorganic nanoparticles with biocide properties are pure metals such as silver, gold, iron, aluminium, cadmium, cobalt, zinc, and copper, as well as UV photo exited metal-oxides comprising TiO2, FeO2, Fe3O4, SiO2, CeO2, WO3, and ZnO2 [15-20]. However, some concerns for use in biomedical applications were raised since they are activated under UV radiation. UV photo-excited nanoparticles induce the generation of pairs of electrons and holes, which react with water and oxygen to yield Reactive Oxygen Species (ROS) that have been proven to damage microbial membrane, triggering controlled cellular processes. Nonstoichiometric metal oxide nanomaterials such as WO3−x, SiO2−x, or TiO2-x have recently shown efficient photoactivation even in visible and Near-Infrared (NIR) light frequencies. The oxygen defects in the structure induce strong Local Surface Plasma Resonance (LSPR) and strong photo-absorption in a broad wavelength range of the NIR region [20]. It appears, hence, that there are several opportunities to create advanced intelligent materials that can kill bacteria without harming other higher organisms. This could be a critical distinction as biosafety regulatory issues and clinical impacts are considered. The European Food Safety Authority (EFSA), responsible for assessing health risks related to food for human and animal consumption, has issued scientific opinions on emerging risks of nanostructured materials [21].

The long-term success of an orthopaedic implant largely depends on the extent of its osseointegration in the surrounding bone. In recent decades, there have been several attempts to develop porous metal structures and coatings to maximize bone ingrowth on prosthesis surfaces. Innovative Additive Manufacturing (AM) technologies, which are based upon building components by adding layers of material rather than by removing material from a raw shape, can provide a breakthrough solution to overcome the significant limitations of the existing technologies and enhance the performance of porous scaffolds significantly. This article reviews the latest developments in EBM technology applied to prepare highly biocompatible porous materials such as Trabecular Titanium and the production of orthopaedic prostheses with enhanced characteristics. While Additive Manufacturing (AM) technologies continuously improve orthopedic implants’ shape and mechanical performance, few solutions have optimised new bone growth and osseointegration without sacrificing device performance. Our perspective study falls in the new Horizon Europe program (Pillar 2 cluster 1, Health, “Tackling diseases and reducing disease burden: identifying new prevention, diagnostics, vaccines, therapies, alternatives to antibiotics”). The new materials have the potential to accelerate the transition to a novel, improved implant device production, exploiting the potentiality of innovative manufacturing technologies and treatments [22,23]. In particular, to develop novel coating technologies for maxillofacial and orthopaedic implants to enhance implant osseointegration and prevent early and late bacterial infections. By considering data on orthopaedic implants failure and occurrence of associated infections (revisions close to 10% of the primary operations; loss of 6 15% within ten years after implantation; periprosthetic infection occurrence in 1-2% of all primary implant surgeries, 8% for revision surgeries), it is immediately apparent that the research outcome not only could represent an up-and-coming market but will also be able to improve the patients’ life-quality drastically. It should also be considered that the highest cost is nowadays on the hospital stay and surgery: the time the patient spends in the hospital can be primarily reduced by the adoption of implants with improved osseointegration and antibacterial performance, especially in surgery where the part has to be partially or reconstructed (examples: pelvis, mandible, cheekbone). At the same time, these characteristics will drastically reduce hospitalisation time. A prosthesis or fixation device designed to include both osseointegration and antibacterial/ bioactive properties will reduce the possibility of failure (aiming at reducing at less than 5% within ten years after implantation) and the cost for the secondary actions.

1. Shah KW, Huseien GF (2020) Inorganic nanomaterials for fighting surface and airborne pathogens and viruses. Nano 1(3): 032003.
2. Mathew TV, Kuriakose S (2013) Studies on the antimicrobial properties of colloidal silver nanoparticles stabilized by bovine serum albumin. Colloids Surf B Biointerfaces 101: 14-18.
3. Peters T (1995) All about albumin: Biochemistry, genetics, and medical applications. Academic, New York, USA.
4. Aversa R, Petrescu RV, Apicella A (2019) A nanodiamond for structural biomimetic scaffolds, Engineering Review 39(1):81-89.
5. Aversa R, Petrescu RV, Apicella A, Petrescu FIT (2020) Biologically structured materials. Independent Journal of Management & Production 10(8): 1119-1139.
6. Liu T, Chen Y, Apicella A, Mu Z, Yu T, et al. (2020) Effect of porous microstructures on the biomechanical characteristics of a root analogue implant: An animal study and a finite element analysis. ACS Biomater Sci Eng 6(11): 6356-6367.
7. Apicella D, Veltri M, Balleri P, Apicella A, Ferrari M (2011) Influence of abutment material on the fracture strength and failure modes of abutment-fixture assemblies when loaded in a bio-faithful simulation. Clinical Oral Implants Research 22(2): 182-188.
8. Sorrentino R, Apicella D, Riccio C, Gherlone E, Zarone F, et al. (2009) Nonlinear visco-elastic finite element analysis of different porcelain veneers configuration. J Biomed Mater Res B Appl Biomater 91(2): 727-736.
9. Tiller JC, Liao CJ, Lewis K, Klibanov AM (2001) Designing surfaces that kill bacteria on contact. Proc Natl Acad Sci USA 98(11): 5981-5985.
10. Cen L, Neoh KG, Ying L Kang ET (2004) Surface modification of polymeric films and membranes to achieve antibacterial properties. Surf Interf Anal 36(8): 716-719.
11. Usman MS, ME El Zowalaty, Shameli K, Zainuddin N, Salama M, et al. (2013) Synthesis, characterization, and antimicrobial properties of copper nanoparticles. Int J Nanomed 8: 4467-4479.
12. Marais F, Mehtar S, Chalkley L (2010) Antimicrobial efficacy of copper touch surfaces in reducing environmental bio burden in a South African community healthcare facility. J Hosp Infect 74(1): 80-82.
13. Gramanzini M, Gargiulo S, Zarone F, Megna R, Apicella A, et al. (2016) Combined microcomputed tomography, biomechanical and histomorphometric analysis of the peri-implant bone: A pilot study in minipig model. Dental Materials 32(6): 794-806.
14. Aversa R, Petrescu FIT, Petrescu RV, Apicella A (2016) Biomimetic FEA bone modeling for customized hybrid biological prostheses development. American Journal of Applied Science 13(11): 1060-1067.
15. Nikolova MP, Chavali MS (2020) Metal oxide nanoparticles as biomedical materials. Biomimetics 5(2): 27.
16. Teleanu DM, Chircov C, Grumezescu AM, Volceanov A, Teleanu RL (2018) Impact of nanoparticles on brain health: An up-to-date overview. Journal of Clinical Medicine 7(12): 490.
17. (2019) EFSA statement on the review of the risks related to the exposure to the food additive titanium dioxide (E171) performed by the French Agency for Food. EFSA (European Food Safety Authority) - EFSA Journal, Wiley Online Library.
18. Shah KW, Li W (2019) A review on catalytic nanomaterials for volatile organic compounds VOC removal and their applications for healthy buildings. Nanomaterials 9(6): 910.
19. Cetal Z (2018) Zero-dimensional, one-dimensional, two-dimensional and three-dimensional biomaterials for cell fate regulation. Adv Drug Delivery Rev 132: 33-56.
20. Netal SP (2018) Nanomaterials history, classification, unique properties, production and market. Emerging Applications of Nanoparticles and Architecture Nanostructures (Amsterdam: Elsevier), pp: 341-384.
21. Dastjerdi R, Montazer M (2010) A review on the application of inorganic nano-structured materials in the modification of textiles: focus on anti-microbial properties. Colloids Surf B 79(1): 5-18.
22. Ratner BD (2007) Polym Int A paradigm shift: biomaterials that heal. Polym Int 56(10): 1183-1185.
23. Beyth N, Yudovin Farber I, Bahir R, Domb AJ, Weiss EI (2006) Antibacterial activity of dental composites containing quaternary ammonium polyethylenimine nanoparticles against Streptococcus mutans. Biomaterials 27(21): 3995-4002.