Surgical site infections (SSIs) are one of the worst adverse events in surgery, since they are associated with longer post-operative hospital stays, additional surgical procedures, treatment in intensive care units and often higher mortality. The incidence of SSI in developed countries averages around 2–3%. This level of risk is significantly higher in developing countries, where SSI rates 1.2 to 23.6 per 100 surgical procedures [1]. In the past 70 years, antibiotics have been crucial in the fight against infectious diseases caused by bacteria and other microbes, being an important reason for the increase of average life expectancy in the 20th century. But just few years after the mass-production of antibiotics, microbes began to resist them, and antibiotics were at risk of becoming useless. Anti-Microbial Resistance (AMR) is the cause of an increase of health care cost due to longer duration of illness, additional tests and use of more expensive drugs and it is associated to an increased risk of compromised clinical outcomes, consuming more health-care resources. New resistance mechanisms are emerging and spreading globally, threatening our ability to treat common infectious diseases and resulting in prolonged illness, disability, and death [2]. Today, the control and prevention of infection diseases is one of the topics of the 2030 Agenda for Sustainable Development adopted by all United Nations Member States in 2015 (Sustainable Development Goal 3: Ensure healthy lives and promote well-being for all at all ages) [3].
Polymethylmethacrylate (PMMA) based bone cements are commonly used for artificial joints fixing and as fillers for large bone defects in orthopaedic surgery [4] due to their fast primary fixation to the bone. However, the interface between bone cement and bone has been recognized as a weak-link zone, both mechanically and biologically [5], as well as for its predisposition to bacterial contamination and, in turn, the risk of being preferential site of surgical infection. The bacterial adhesion on the cement surface can be prevented by favoring their fast bone-bonding ability and with this purpose, the addition of a bioactive fillers, like hydroxyapatite, bioactive glasses and glass-ceramics, represents a common approach [6–11,]. Another strategy to counteract the bacterial contamination is to load the bone cements with antibiotics, like gentamycin, vancomycin or others [9, 12–15], but these formulations are mainly indicated for revision surgery, due to some relevant drawbacks of antibiotic-loaded bone cements [16, 17], including the risk of developing antibiotic-resistant strains, that strongly limits their use in prophylaxis.
Aiming to prevent the increase of multiresistant bacteria and to reduce the incidence of periprosthetic infections, some antibiotic-free antibacterial bone cement formulation were investigated in literature, for example loading bone cements with silver nanoparticles [9, 18–21], or adding a variety of antibacterial additives together with bioactive fillers [9, 22, 23], but the antibacterial properties of these formulations, as well as the bone cement handling and its mechanical properties still need optimization [24].
A completely different approach has been patented by Vernè and co-workers [25], who developed a composite bone cements consisting in a PMMA matrix loaded with silica-based silver-doped bioactive glass particles. Bioactive glasses (BGs) are worldwide known as optimal materials for the realization of bone substitutes as well as coatings on metallic devices, and can be treated to enrich their surfaces with a variety of active ions [26, 27].
The use of silver-doped bioactive glasses as additional phase into PMMA-based bone cements has been previously proven, by the authors of the present paper, to be safe and effective in various commercial bone cements, having different compositions and viscosities [28–32]. For each of the investigated composite formulations, deep studies have been carried out in order to assess the most effective glass synthesis methods, as well as the proper amount and grain size of the antibacterial and bioactive glass particles, to modulate the bioactive and antibacterial ability of the implant. On the base of these previous studies, the ion-exchange process has been recognized as a good and versatile technique for the synthesis of the bioactive and antibacterial glasses, since it allows introducing a controlled and reproducible silver amount in the glass network without affecting its bioactivity, by tailoring the process parameters: temperature, time concentration and pH of the solution [29]. The composite bone cements object of the above mentioned previous studies have been suggested as very promising formulations due to the following proven advantages:
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Their bioactive and antibacterial properties are imparted by a unique inorganic phase (i.e. there is no need of embedding too many additional phases into the bone cement).
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The silver ions release can be tailored and assured for a prolonged time, if necessary, by a correct design of the glass composition.
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The mechanical compressive strength of the composite bone cement is unaffected in comparison with the plain bone cement and are still in agreement with the ISO 5833 standards.
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The biocompatibility of the plain bone cement is maintained.
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The antimicrobial effect has been demonstrated towards the most common bacterial and fungal strains.
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The bioactive and antibacterial glasses possess intrinsic radio-opacity, so the use of traditional radio-opaque additives, in addition to the glass, is no longer needed.
These advantages let foresee, in case of future clinical uses, an important reduction of implant septic loosening incidence and a significant decrease of antibiotic treatments due to periprosthetic infections.
For a better assessment of the potentiality of this innovative approach to surgical site infection prevention, in the present paper the method for the preparation of composite bone cements containing bioactive and antibacterial glass particles has been further optimized and investigated. Since it was already reported by the authors that different viscosities of the bone cement seem not to influence the composites handling and the glass distribution in the PMMA matrix [30], in the present paper a high viscosity commercial bone cement was used as polymeric matrix and the study was focused on the effect of glass particle size on the composite cement mechanical properties, in particular bending strength, without altering the bioactive and antibacterial behaviour induced by the dispersed glass particles, as well as the setting properties of pristine cement.