Polymers in Biomedical Applications: Comparison
Please note this is a comparison between Version 1 by Buddhika Sampath Kumara and Version 2 by Jessie Wu.

Bacterial infections and antibiotic resistance remain significant contributors to morbidity and mortality worldwide. Despite recent advances in biomedical research, a substantial number of medical devices and implants continue to be plagued by bacterial colonisation, resulting in severe consequences, including fatalities. The development of nanostructured surfaces with mechano-bactericidal properties has emerged as a promising solution to this problem. These surfaces employ a mechanical rupturing mechanism to lyse bacterial cells, effectively halting subsequent biofilm formation on various materials and, ultimately, thwarting bacterial infections.

  • antibacterial surfaces
  • nanofabrication
  • antimicrobial
  • polymeric implants

1. Introduction

Bacterial cells usually attach to surfaces, colonise, and form a matrix of polysaccharide material called biofilms. Bacteria can adhere to many different surfaces, including human tissues, metals, and polymeric surfaces [1]. The bacteria that form biofilms are highly resistant to disinfectants, antiseptics, and other antimicrobial agents that are normally effective in their planktonic state [2][3][4][2,3,4]. Moreover, overuse of antibiotics has led to an era where bacteria are becoming increasingly resistant to antibacterial agents, making it more difficult to treat infections [4][5][4,5]. The discovery of the mechano-bactericidal response to nano-topography found on insect wings, such as cicadas and dragonflies, has inspired the development of nanostructured topography on synthetic materials, which can reduce or inhibit the growth of bacteria on their surfaces. Most of the studies on artificial antibacterial micro/nanostructured surfaces were based on materials like ceramics, metals, and alloys, because of their superior mechanical and thermal properties that lead to potential applications in medical and industrial sectors. Metals are among the most used engineering materials and are employed extensively as biomaterials [6][7][6,7]. However, they can cause inflammation, bone loss, and imaging artifacts in computed tomography (CT) scans and magnetic resonance imaging (MRI) due to their magnetic properties, low flexibility, and low biocompatibility compared to biocompatible polymers [8][9][8,9]. High cost and density characteristics also make them less effective in specific medical implants such as cardiovascular implants, absorbable implants, paediatric implants, and cochlear implants [9][10][11][12][13][14][15][9,10,11,12,13,14,15]. Biocompatible polymers are attractive alternatives that can be used in such applications due to ease of processing, low weight, high biocompatibility, and biodegradability [16][17][18][19][16,17,18,19]. The methods for developing nanostructured bactericidal surfaces have been reviewed in the recent literature [20][21][22][23][24][20,21,22,23,24]. However, a comprehensive and critical overview of the techniques developed for polymers is yet missing.

2. Polymers Used in Biomedical Applications

Many biocompatible polymers are used in medical implants with some demonstrating high biocompatibility [25]. The most commonly used biocompatible polymers are polyglycolic acid (PGA) [26][27][26,27], poly(lactic-co-glycolic acid) (PLGA) [26][28][29][30][26,28,29,30], polycaprolactone (PCL) [26][31][32][26,31,32], polyurethane (PU) [33], polyvinyl alcohol (PVA) [34][35][36][34,35,36], silicone [33][37][38][33,37,38], polylactic acid (PLA) [26][39][40][41][42][43][44][26,39,40,41,42,43,44], polypropylene (PP) [45][46][45,46], and polymethyl methacrylate (PMMA) [47][48][49][47,48,49]. Each polymer has distinct advantages and limitations in various biomedical applications, as mentioned in Table 1. For instance, PMMA is a frequently used polymer for dental implants due to its non-degradability and high strength while PLA is used in bone tissue engineering applications due to its biodegradability and osteoblast stimulation [39][50][39,50]. Moreover, polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) are emerging biomedical materials with high biocompatibility, thermal stability, and non-degradability with excellent mechanical properties which are suitable for various biomedical applications [51][52][51,52]. In such applications, one of the most concerning issues is implant failures due to bacterial infections as described in the Introduction section. Bacteria colonise various implant surfaces, such as dental implants, catheters, and orthopaedic implants [53]. Furthermore, antibiotic resistance directly contributes to implant failures due to the formation of biofilms on these surfaces [54][55][54,55]. In response to this concern, numerous studies have been undertaken to develop physical and chemical methods aimed at reducing bacterial colonisation [56][57][56,57]. To implement these strategies successfully, the choice of implant material plays a pivotal role in developing surfaces that are bactericidal and/or antifouling. Among various materials, polymers offer advantageous characteristics for biomedical implant applications. These attributes are highly considered in the biomedical field, particularly for ensuring a successful implant surgery in in vivo conditions (Figure 1).
Figure 1. Driving factors to choose a polymer as implant material. Compared to other materials polymers provide some favourable characteristics for biomedical implant applications, which is essential in the biomedical field for successful implant in in vivo applications.

3. Mechanism of Bacteria Adhesion on Surfaces

Bacteria are present in different environments, such as animals, soil, plants, fresh water, and air [91]. Bacterial adhesion refers to the capability of bacteria to attach to a range of surfaces, such as human tissues, medical implants, polymers, metals, and glasses [92]. This process is vital for bacterial colonisation and is achieved through a complex process that involves few stages with multiple factors. As an overview, it is affected by the distinct characteristics of bacteria such as motility, cell wall structure and appendages (flagella, pili, and curli), exposure duration to the surface, amount of nutrients, coaggregation, cohesion, and bacterial density [92][93][94][92,93,94]. Bacteria colonisation occurs in two stages: (1) prior attachment stage, known as the primary stage or reversible adhesion, and (2) post-attachment stage, known as the secondary stage or irreversible adhesion [95]. During the reversible (volatile) adhesion, once the bacteria reach a certain proximity from the surface, their adhesion depends on the superposition of attractive and/or repulsive forces such as electrostatic, van der Waals, hydrophobic, and hydrodynamic forces [95], whereas the attraction of the bacteria to the surface is high during this stage and occurs within few minutes [96]. The majority of bacteria carry a predominantly negative surface charge [97][98][97,98], especially in the initial growth stage [98], and tend to selectively bond with surfaces that are positively charged [99]. However, if the environment (where the bacteria and surface are located) is in high ionic condition, then this electrostatic interaction will be reduced due to the charge screening effect (neutralizing) caused by oppositely charged ions in the environment [93][99][93,99]. In the second stage, adhesion becomes irreversible (permanent) without any need for physical or chemical intervention, firmly anchoring the organism to the surface within several hours [95][99][95,99]. Similar to the primary stage, van der Waal interactions are involved, which are between the outer cell wall and the surface. Moreover, polysaccharides and proteins play a crucial role in the transition from reversible to irreversible cell attachment, whereas the irreversible attachment is mostly dominated by the production of extracellular polymeric substances (EPSs) [92][99][100][92,99,100]. EPSs consist of polysaccharides, proteins, extracellular DNA, and lipids. EPSs, which are released by cells in biofilms adhered to surfaces, protect against mechanical damage and shear generated by flow [99]. Notably, within biofilms, EPSs exhibit a non-homogeneous distribution pattern among cells [101]. In the biofilm, an EPS offers various advantages to the cells. These benefits include adhesion, protection, and structural support. Specifically, the aggregative polysaccharides function as molecular glue, facilitating the adhesion of bacterial cells both to each other and to surfaces [102]. In addition to these factors, the surface characteristics of the substrate, including factors like surface charge density, wettability, roughness, stiffness, and surface architecture, are also regarded as significant factors that influence the initial adhesion of bacteria to surfaces [94]. Once these bacterial cells colonise a surface, they can create numerous problems such as infections. Many different methods are used to mitigate bacterial colonisation.
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