Antimicrobial surfaces in biomedical engineering and healthcare
biomaterials
Abstract
The presence of harmful microorganisms (such as bacteria, fungi, and viruses) in biomedical items
significantly contributes to the occurrence of hospital-acquired infections (HAI), which
substantially burdens the healthcare system. The imperative to reduce patient-related illnesses in
healthcare settings necessitates the advancement of biomaterials capable of impeding surface
contamination. This article overviews contemporary antimicrobial approaches, focusing on novel
antimicrobial biomaterials and antimicrobial surface topographies inspired by the natural world.
There has been a recent uptick in applying these developments to the creation of biomedical
engineering devices.
Keywords: Antimicrobial surfaces, Biomaterials, Biomedical engineering.
Introduction
The purpose of this introductory section is to provide an overview of the topic at hand and set
before the onset of the SARS-CoV-2 pandemic. It was approximated that Healthcare-Associated
Infections (HAIs) were responsible for causing around 100,000 deaths per year in the United States
and 37,000 deaths per year in Europe. The healthcare system experiences a considerable financial
burden, with a total of V7 billion allocated alone for this purpose in Europe [1]. The primary
etiological agents of healthcare-associated infections (HAIs) are bacteria, with Pseudomonas
aeruginosa being a prominent example. However, certain species of fungi, such as Candida auris,
and viral strains, including norovirus, have also been implicated in HAIs [2,3]. Additionally, crossinfection has been identified as another significant factor contributing to the prevalence of HAIs.
The ongoing global pandemic has heightened public consciousness regarding the significance of
adhering to optimal strategies to mitigate the transmission of germs. These strategies encompass
several measures, including but not limited to social distancing, hand cleanliness, and the
utilization of face masks. According to the European Centre for Disease Prevention and Control
(ECDC) [4], implementing these measures has contributed to a decline in the transmission of not
only SARS-CoV-2 but also various other infectious diseases that require notification. A notable
surge of interest has been in developing novel antimicrobial surfaces and biomaterial coatings.
These advancements are specifically designed to successfully mitigate the risk of microbial
contamination and the subsequent transmission of illnesses [5]. The hospital setting has witnessed
the emergence of novel antimicrobial fibre technologies as a feasible approach to tackle the
problem of contamination and the spread of sickness through fabrics [6]. Showcases the notable
antimicrobial effectiveness of a newly developed material using gallium liquid metal copper alloy
(LMCu) particles. This material demonstrates substantial capabilities in combating bacterial,
fungal, and viral infections [7]. The progress in developing these textiles holds great promise for
significantly contributing to the fight against SAR-CoV-2. This contribution may be observed in
various aspects, such as enhancing personal protective equipment (PPE) utilized by healthcare
personnel, including coats, masks, and uniforms.
Additionally, these textiles can improve the quality of bed and bath linens and gowns for patients
[8]. Furthermore, various biomedical implanted devices, catheters, prostheses, contact lenses,
medical instruments, respiratory machines, and other tools commonly seen in hospitals can
potentially be sources of healthcare-associated infections (HAIs) [9]. Over several decades,
microbes have developed strategies to circumvent various microbial disinfection and
decontamination methods. The ability to produce biofilms and the emergence of multidrugresistant microbes have contributed to this accomplishment [10,11]. As a result, managing
healthcare-associated infections (HAIs) becomes ever more difficult, typically requiring prolonged
rounds of intravenous systemic antibiotic treatment. Assuming the situation remains unresolved
and progresses to a severe stage, it may lead to the development of septicaemia. In such instances,
surgical intervention may be required to eradicate the infected device and necrotic tissue and drain
any abscesses [12]. Therefore, it is crucial to develop novel strategies to address the issue of
multidrug-resistant (MDR) bacteria contamination, proliferation and spread on diverse surfaces,
particularly those linked to medical implants. The convergence of biomedical engineering and
materials science methodologies yields notable progress in antimicrobial research, culminating in
innovative and dynamic discoveries. Antimicrobial surfaces commonly elicit many interactions
with microorganisms, including physical, chemical, or biological. This review classifies
antimicrobial surfaces into three discrete types. The proposed research involves the investigation
of three distinct surface functionalities: Characters exhibiting anti-adhesive and anti-biofouling
characteristics,Surfaces including biocides for controlled release and Photocatalytic surfaces.
Emerging antimicrobial materials and strategies
Anti-adhesive surfaces
Surfaces with anti-adhesive and antifouling properties reduce microbial attachment to solids and
prevent biofilm development. Adhesion can be diminished by employing superhydrophobic
characters, zwitterionic polymers, or modifying the nanostructure [14,15]. Instead of antibiotics, a
possible alternative is to change implant materials using physically tailored solutions to regulate
bacterial colonization [16]. The surface's topography may successfully lessen fouling. Micro- and
nano-structured surfaces in nature prevent bacterial adherence without killing them, as shown in
Figure 3. Antifouling agents include lotus leaves, shark skin, and rose petals. The micro-nano
structure of many insects serves as a barrier against bacteria. Specifically, biomimetic
antimicrobial surface structures [17–19] have been inspired by the phenomena and used in
biomedical engineering. The lysis of a bacterial cell, according to a theory put forward by Ishak et
al. [20]. However, new studies have introduced alternative paradigms to those of Ishak et al.
According to research by Wu et al. (2019), bacterial cell membrane stretching is affected by the
density and height of nanostructures [21]. While the models have shed light on the mechanism,
their applicability has been limited due to the complexity of the interactions between bacteria and
substrates. Therefore, further research is required to determine the forces to penetrate the cell wall
[22]. Hasan et al. created a nanoscale topography effective against bacteria and viruses. Tests were
performed using aluminium 6063 disks. The disks were etched with sodium hydroxide for three
hours to create ridges and improve hydrophilicity. Nanoindentation tests showed exceptional
mechanical capabilities of nanostructured surfaces. The first documented nanostructure having
antibacterial and antiviral capabilities, this discovery is significant. Therefore, it holds significant
potential in reducing the transmission of infections from different types of physical surfaces [23].
The coordinated efforts of Wei et al. have resulted in an important recent advancement in this field.
The study utilized vertical silicon nanowires (SiN) arrays and conducted experiments to assess
their biocidal properties. The results of these studies revealed interesting discoveries, suggesting a
limited presence of bactericidal activity on the surface. The bactericidal properties were
successfully demonstrated with the inclusion of a lysosome. The SiN-PMAA/Lys surfaces showed
a remarkable efficacy of over 95%. The results of this study highlight the significance of the
surface's topography and wide surface area in maintaining lysosomes despite the absence of
bactericidal activity. As a result, this led to the eliminating of both floating and attached bacteria
[24]. This study differed from previous studies in its experimental design by highlighting the
potential misinterpretation of findings that attribute the inhibition of bacterial adhesion solely to
topographic signals. This phenomenon can be attributed to the correlation between topographic
cues and the chemical properties of the coatings' components. The absence of clear differentiation
in these studies has been found to have detrimental effects on understanding antimicrobial
surfaces. Therefore, future experimental frameworks must address this issue by including control
samples that lack chemical action [25]. The technological challenge of producing bioinspired
surfaces on a wide scale in a cost-effective manner is an aspect that requires attention [26].
Significant advancements have been achieved in this domain, as a range of procedures can be
effectively employed for diverse materials. The authors Ozkan et al. conducted a study in which
they employed aerosol-assisted chemical vapour deposition (AACVD) to synthesize polymer films
coated with copper that exhibit superhydrophobic and antibacterial properties. The combination of
polydimethylsiloxane (PDMS) and copper nanoparticles (CuNPs) in the AACVD process resulted
in the effective fabrication of a unique surface with superhydrophobic and antibacterial properties
[27]. Various natural surfaces possess bactericidal properties, including the wings of cicadas and
dragonflies. The ongoing studies demonstrate these natural bactericidal compounds' potential
[17,28,29]. To investigate the impact of surface topography on the interactions between bacteria
and surfaces, Flynn et al. fabricated several replicas of cicada wings using polypropylene glycol
(PEG) materials. Water-swollen polyethene glycol (PEG) facilitated the regulated generation of
bigger pillars, improving bactericidal effectiveness [30]. Furthermore, Fisher et al. studied surfaces
patterned with diamond nanocones, which serve as biomimetic counterparts to the bactericidal
cicada fly wing. The researchers noticed the antibacterial properties of these surfaces. The
researchers created two diamond nanocone surfaces and subsequently used scanning electron
microscopy (SEM) to analyze and characterize their morphology [16]. The observation results
indicated surface B exhibited notably greater bacterial activity than surface A. The findings of this
study are significant because they show that surface B, with its size variety, nonuniformity, and
reduced density of nanocone arrays, may increase bacterial activity [16]. Green et al., who studied
the antibacterial characteristics of gecko skin and compared it to other materials, found results
consistent with those in the present work. The methods by which bacteria rupture on surfaces have
been the subject of numerous physical theories. Compression, stretching, tearing, and piercing are
all included in these models [31]. More research is needed to determine what mechanism gives
these naturally-inspired surfaces superior killing efficiency. Despite the promising results seen
with these surfaces, more research is required to grasp the underlying concepts and tools [32].
Biocidal/biostatic surfaces
Contact-active antimicrobial surfaces function by effectively eliminating microorganisms without
the need for the dissemination of biocidal agents. In general, two approaches are commonly
employed. The first approach involves optimizing a spacer effect, wherein the biocide is tethered
to the surface via a polymer chain. This arrangement facilitates the biocide's ability to access and
disrupt the cytoplasmic membrane of the bacteria. The second approach involves using positively
charged quaternary ammonium compounds (QACs), effectively eliminating bacteria by displacing
phospholipids from their cell membranes [34].Antimicrobial polymers have emerged as a potential
field of study in the fight against microbial contamination. This is primarily owing to their flexible
chemistry, which allows for the customization of properties and performance [35]. Polymeric
materials with inherent antibacterial properties have garnered significant attention due to their
innate ability to combat microbial growth. Recent studies have discovered that composite films
containing hyaluronic acid exhibit bacteriostatic properties [36e 38]. The mechanical and
antibacterial performance of produced films was enhanced by including carbon nanofibers. The
materials mentioned above were specifically identified as promising therapeutic coatings for
dressings intended for wound healing [39]. A subsequent investigation revealed that the
bactericidal properties of a Schiff base derived from O-amine functionalized chitosan were
superior to those of chitosan and O-amine functionalized chitosan counterparts [40]. Antimicrobial
peptides are a class of naturally derived antimicrobials with a wide range of antimicrobial
properties. These peptides can potentially serve as a viable substitute for traditional antibiotics.
Using bioinspired antimicrobial peptides (AMPs) in fabricating materials has emerged as a
promising approach for combating infectious diseases and inhibiting bacterial adhesion and
biofilm formation on various surfaces. Antimicrobial peptides (AMPs) possess the potential to be
modified to achieve a wide range of antimicrobial effects. They have demonstrated notable
efficacy against bacteria resistant to conventional antibiotics while displaying exceptional
biocompatibility [41,42]. Numerous microorganisms and diseases exhibit a high degree of
resistance to targeted eradication owing to the intricate nature of their membranes. The utilization
of computer-aided design in the analysis of antimicrobial peptides (AMPs) enables the collection
of essential data regarding chemical properties and biological activities within AMP sequences.
This facilitates the development of predictive models that can evaluate the antibacterial potential
of a candidate sequence before its chemical synthesis [43]. Furthermore, utilizing bioinformatics,
protein engineering, and de novo design [44] provides an opportunity to computationally create
antimicrobial peptides (AMPs) with targeted efficacy against certain viruses. Several research
studies have been conducted on utilizing hybrid polymeric/metal antimicrobial coatings in recent
years. Hazer et al. (year) conducted a study investigating the antibacterial characteristics and
biofilm formation inhibition of Titanium screws coated with polymer-based Ag nanoparticles
(NPs). The screws that underwent modifications showed potential as they could withstand tapping
stresses, as evidenced by the continued presence of Ag NPs on their surface even after 21 days
following implantation in rabbits [45]. Although these studies exhibit promising antibacterial
properties, they are not devoid of dispute due to their metallic composition. Regrettably, the
existing body of research on hybrid polymeric-metal coatings is insufficient in simultaneously
investigating the impact of these coatings on bacteria and eukaryotic cells [46]. Multifunctional
sustainable hydrogels derived from lignin have demonstrated significant promise as prospective
materials for healthcare applications due to their robustness, elasticity, potent antimicrobial
properties, adhesive nature towards skin tissue and diverse surfaces, and ability to self-repair [47].
One promising contemporary strategy for the prevention of bacterial infections involves the
application of antibacterial biomaterials onto the surfaces of medical devices, which aids in
reducing bacterial adhesion [48]. Bacteria tend to adhere to tissue surfaces or implants and
concurrently generate extracellular polymeric substances (EPS) that facilitate the formation of
bacterial biofilms. These biofilms frequently lead to the development of pathogenic illnesses
[49,50]. In recent times, polymer coatings have demonstrated significant efficacy in addressing the
issue of microbial proliferation. Using anti-adhesive coatings in conjunction with bactericidal
surfaces has shown potential synergistic outcomes. A reversible, non-leaching antibacterial surface
that modifies hierarchical polymer brush structure to adapt to bacteria was studied by Yan et al.
The experimental approach required incorporating a pH-responsive polymer outer layer into the
bactericidal background layer. This exterior layer worked as an actuator to regulate hierarchical
surface attributes, as shown in Figure 1 [51]. By altering pH, the hierarchical surface can switch
between bactericidal and bacteria-repellent properties [52]. The persistence of the surface's
antimicrobial efficiency would be improved by studying multifunctional materials with adaptive
antibacterial capabilities without additional antimicrobial chemicals [53]. Semi-interpenetrating
polymer networks (SIPN) were developed by Zhao et al., and they have antifogging and
antibacterial properties. Hydrophobic quaternary ammonium contributed to antibacterial effects,
while the hydrophilic/hydrophobic balance was responsible for antifogging. These coverings
rendered Gram-positive and Gram-negative bacteria ineffective [54]. There is a need for more
information about modern multifunctional coatings since more study is needed. These coatings are
a step forward in antimicrobial surface technology due to their multifunctionality, which
safeguards patients [25]. Urinary catheters with a pH-sensitive hydrogel coating were described
by Milo et al. (year). The coating has two antibacterial protection layers, as Milo et al. defined.
Urine pH increases owing to infection, causing the poly (methyl methacrylate-co-methacrylic acid)
layer to enlarge and release a dye, resulting in a noticeable colour change. The surface inhibited
bacterial growth and provided early warning of illness. The only way to stop the spread of a
pathogen is to identify it quickly. Therefore, more study of related chemicals is warranted [55].
However, since human pH can vary, various triggers have been investigated [56]. The hydrogel
developed by Zhou et al. reacts to the poisons or enzymes pathogenic microorganisms release.
Incorporating GelMA hydrogels into wound dressings resulted in the selective inhibition of
pathogenic germs. To identify infections, a hydrogel matrix was designed with a blister that
contained a dye that fluoresced when diluted due to vesicle membrane breakdown. This
mechanism's ability to detect illness, combat harmful microbes, and heal wounds shows
considerable promise [54]. Hydrogels are useful in preventing antibiotic resistance because they
may adapt to biological cues and activate when necessary (56).
Photocatalytic surfaces
Photocatalytic oxidation is being studied as a potential replacement for antimicrobial coatings in
healthcare. Surfaces like these typically contain photocatalytic metal oxides like titanium dioxide
(TiO2), which, when exposed to ultraviolet-A (UV-A) radiation, oxygen, and water, produce
hydroxyl radicals (OH). Figure 4 shows that the OH radicals are highly effective at killing bacteria.
The utilization of titanium dioxide (TiO2) for photocatalytic applications has recently gained
significant popularity. This can be attributed to its remarkable characteristics, such as noteworthy
stability and photoactivity, cost-effectiveness, and non-toxic properties [57]. Titanium dioxide
(TiO2) has some limitations, such as a substantial band gap and heightened recombination
rates.Consequently, it is frequently subjected to metal oxide modifications [58]. In their study,
Pedroza-Herrera et al. synthesized copper-doped titanium dioxide (TiO2) nanoparticles using the
sole gel deposition method, followed by microwave hydrothermal treatment. Their research
significantly reduced the band gap of the nanoparticles through a modest amount of doping. The
nanoparticles have notable antibacterial characteristics while demonstrating no cytotoxic effects
on blood cells. The approach described in this study combines the photocatalytic oxidative
mechanism with the leaching process of copper ions, resulting in significant antibacterial efficacy
[59]. In addition to metallic materials, non-metallic elements, namely SiO2, nitrogen, and fluorine,
can be employed as modifiers for TiO2, enhancing its photocatalytic performance while exhibiting
negligible toxicity levels. The hybrid nanocomposite consisting of TiO2 nanoparticles and
bacterial cellulose, doped with fluorine and nitrogen, was developed by Janpetch et al. The material
exhibited an increased sensitivity to visible light. It showed a significant disinfection activity when
exposed to fluorescent light, effectively targeting Gram-positive and Gram-negative bacteria [60].
The fabrication of these photocatalytic coatings is achieved through a thermal spray approach. The
procedure above represents a single-step manufacturing method that involves chemical synthesis
and element doping. This technique can potentially be utilized in developing anti-fouling selfcleaning surfaces, as well as for visible light-induced sterilization, as indicated by references
[61e64]. The thermal spray approach has demonstrated efficacy in the production of photocatalytic
coatings. However, the existing literature on this application and its associated disinfection
mechanisms must be improved, indicating additional scholarly investigation is required.
Final considerations
This review provides an overview of the most recent materials and methodologies utilized in
advancing and auguring antimicrobial surfaces. The utilization of coatings that exhibit controlled
release of antimicrobial compounds upon the adhesion of certain microorganisms to the surface is
yielding encouraging outcomes. Polymers and biopolymers play a prominent role in this
technological field, and integrating multifunctionality into their mechanisms holds promise for
addressing the contemporary challenge of antibiotic resistance in medicine. Hybrid polymericmetal coatings have undergone notable progress, yet they are presently subject to dispute due to
their potential adverse effects on eukaryotic cells. Incorporating investigations into these materials'
cellular and antibacterial properties is crucial for future study. Stimuli-responsive hydrogels
represent a significant category of biomaterials that has garnered increasing attention in recent
years. Enzyme-responsive gels have garnered considerable attention in the scientific community
due to their dual functionality of directly targeting bacteria and identifying illnesses at an early
stage. There is a growing interest in novel methodologies for developing antibacterial surfaces that
use topographical aspects. Considerable advancements have been achieved in the realm of
manufacturing methodologies employed for the synthesis of these complex surfaces. There is a
growing interest in the utilization of photocatalytic characters that are synthesized by thermal spray
techniques. Integrating many antimicrobial strategies can enhance the efficacy of combating
pathogenic microbes, hence facilitating the development of multifunctional surfaces that can
effectively mitigate adhesion biofilm formation and exhibit biostatic or biocidal qualities.
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