Nanoparticles for the Prevention and Treatment of Bacterial Biofilms on Orthopedic Implants

Introduction

Orthopedic implants have indubitably enhanced the quality of life for patients with incapacitating bone diseases such as osteoarthritis and bone fractures (Connaughton et al., 2014). Recent times have witnessed substantial advances in the design of orthopedic implants with a focus on enhancing their performance and durability (Caplin & García, 2019). It is estimated that the global market size of orthopedic implants will reach 79.5 billion USD by 2030 (Wu et al., 2022). However, implantation is associated with a risk of infection due to bacterial adherence on the surface of implants (Abouaitah et al., 2021). This is attributed to the fact that ~ 10,000 times lower bacterial load is necessary to colonize an implant as compared to native tissue (Khatoon et al., 2018). The risk of implant-associated infection is enhanced in patients having a compromised immune system (Abouaitah et al., 2021). The rate of implant-associated infections also depends on the condition and lifestyle of the patient such as patients having diabetes mellitus, obesity, smokers, etc. (Billings & Anderson, 2022).

Biofilms are defined as organized clusters of bacteria enclosed in a self-generated matrix. The composition of this matrix varies with the type of species, strain, and environmental conditions. These biofilm bacteria are resistant to conventional antibiotics, immune mechanisms of destruction such as phagocytosis, and adaptive immune responses (Arciola et al., 2012). It is imperative to preclude bacterial adherence and propagation at 6 h after implantation to achieve an aseptic environment at the site of implantation for a longer time, as bacterial adherence at this stage can culminate in biofilm formation on the implant surface (Pawar et al., 2018). Bacterial biofilm-associated infections account for 65–80% of orthopedic implant-associated infections (Wei et al., 2022). Thus, biofilm formation on orthopedic implants remains a grave concern threatening their clinical success (Caplin & García, 2019).

The skin barrier is disrupted during the surgical procedure of implantation and the incorporation of foreign material in the body renders the body vulnerable to infection (Connaughton et al., 2014). Post-implantation there is a race between the host cells and the microorganisms to adhere and colonize the implantation area (Chopra et al., 2021). Implantation of an orthopedic device results in the formation of an immunosuppressed environment termed the immune-competent fibroinflammatory zone which triggers bacterial infection and biofilm formation. Micromovement of the orthopedic device within the host tissue causes suppression of the immune response to bacterial infection. When the orthopedic device moves within the tissue, it releases fragments detrimental to the neighbouring tissue further exacerbating the bacterial infection (Moure et al., 2017).

Staphylococcus, Pseudomonas, and Enterobacteriaceae are the notorious bacteria commonly responsible for serious implant-associated bacterial infections such as prosthetic joint infections. These bacteria are capable of biofilm formation on the surface of implants (Abouaitah et al., 2021). Staphylococcus aureus and Staphylococcus epidermidis account for almost 70% of orthopedic implant infections and Pseudomonas aeruginosa accounts for 8% of orthopedic implant infections (Raphel et al., 2016).