Elsevier

Biomaterials

Volume 84, April 2016, Pages 301-314
Biomaterials

Review
Multifunctional coatings to simultaneously promote osseointegration and prevent infection of orthopaedic implants

https://doi.org/10.1016/j.biomaterials.2016.01.016Get rights and content

Abstract

The two leading causes of failure for joint arthroplasty prostheses are aseptic loosening and periprosthetic joint infection. With the number of primary and revision joint replacement surgeries on the rise, strategies to mitigate these failure modes have become increasingly important. Much of the recent work in this field has focused on the design of coatings either to prevent infection while ignoring bone mineralization or vice versa, to promote osseointegration while ignoring microbial susceptibility. However, both coating functions are required to achieve long-term success of the implant; therefore, these two modalities must be evaluated in parallel during the development of new orthopaedic coating strategies. In this review, we discuss recent progress and future directions for the design of multifunctional orthopaedic coatings that can inhibit microbial cells while still promoting osseointegration.

Introduction

Orthopaedic implant use for joint replacements has been on the rise, with significant increases still projected over the next 15 years [1]. The majority of procedures are knee and hip replacements, with over 700,000 knee and 300,000 hip replacements done annually in the United States [2]. While these surgeries have a track record of decades of positive outcomes, approximately 10% of these implants fail prematurely, within the first 10–20 years, thereby affecting many tens of thousands of patients annually [3]. Furthermore, as the US population continues to age and as life expectancy continues to increase, premature failures are not the only concern; many patients are now outliving their implants. This combination of factors leads to projections of a dramatic increase in implant failures in the near future.

The two leading causes of implant failure are aseptic loosening and infection. While the reported rates of these failures vary depending on the study, approximately 18% of implant failures are due to aseptic loosening while 20% of failures are attributed to infection [4], [5]. Additionally, these issues become even more prevalent in revised total joint arthroplasties. Aseptic loosening can originate from a variety of sources. These include micromotion of the implant relative to the bone during loading, the generation of implant wear particles that lead to inflammation and bone resorption, and poor osseointegration – the functional interface between the implant and the patient's bone [6]. Implant site infections occur as microbes, particularly bacteria, become sessile and adhere to implant surfaces. These solid interfaces provide surfaces for bacterial attachment, proliferation, and biofilm formation, in which the adherent bacteria produce a protective, polymeric, extracellular substance, rendering these bacteria substantially more difficult to eradicate than individual suspended planktonic bacteria floating around the body [7], [8]. A wide variety of bacteria can infect an implant, but a small subset of species makes up the majority of pathogens. Staphylococcus bacteria, most prominently Staphylococcus aureus and Staphylococcus epidermidis, account for close to 70% of orthopaedic implant infections, while Pseudomonas aeruginosa accounts for another 8% of infections [9].

Aseptic loosening and implant infection appear to be mutually exclusive, particularly given the use of the word ‘aseptic’. However, recent studies point to the potential connection between implants that have been reported to fail aseptically and latent occult infections that may have been missed prior to the time of diagnosis [10]. Therefore, even in cases of implant failure where infection was not the primary cause, microbial presence may still play a critical role in initiating or accelerating the failure pathway.

Independently, the problems of aseptic loosening and infection are pressing for the orthopaedics field, and many excellent review articles cover the fields of osseointegration and infection prevention individually [11], [12], [13], [14], [15], [16], [17], [18]. However, the two issues are intimately related, as laid out by Gristina in his description of the “race for the surface”; if the host's cells can reach and occupy the implant surface first, not only will stronger tissue integration be achieved, but a defensive barrier will also be established against microbial attachment and colonization [19]. Strong osseointegration and prevention of infection are both required for a successful implant, necessitating that implant designs consider both criteria simultaneously. In this review we describe several of the specific underlying mechanisms that lead to implant failure either by aseptic loosening or infection and potential design strategies to address these challenges (summarized in Table 1). In particular, with recent progress in understanding the connections between aseptic loosening and infection, this article will highlight recent works that address both problems in concert.

Section snippets

Challenges and potential solutions for osseointegration

Implant osseointegration relies on two distinct requirements. The first is obtaining initial implant stability during surgery, which then lays the groundwork for subsequent osseointegration of the implant as the patient heals. Ensuring implant stability is largely the responsibility of the surgeon and her/his team. Even technological solutions to improve initial implant fit, including automated imaging and robotic arm assistance platforms only assist, rather than replace, the surgery team. The

Challenges and potential solutions for bacterial infection of implants

Infection of orthopaedic implants can have a plethora of consequences, including hospitalization and costly revision surgery [11]. Implant infection has been reported to be the new leading cause of orthopaedic implant removal, overtaking aseptic loosening [4], [72], [73], [74]. Despite the biocompatibility of titanium and its alloys used for implants, bacteria easily and readily colonize these surfaces. Once bacteria adhere to the surface, they begin to proliferate, eventually reaching a high

Future direction

Addressing the clinical challenges of aseptic loosening and implant infection have clearly drawn much attention from the research community. While significant advances have been made in coating technologies to reduce failure either by loosening or infection, the development of technologies to address both challenges simultaneously is ongoing. A clear future direction for the field is the development of multifunctional implant coatings that can effectively balance osseointegration and microbial

Conclusions

Orthopaedic implants are widely used and highly successful treatments for musculoskeletal issues. Their success can be undermined by poor osseointegration and infection, the two leading causes of implant failure and revision surgeries. A variety of strategies have been studied to improve osseointegration and to prevent infection, though typically proposed solutions have only addressed one of the two issues. In this review, we highlighted technologies that have the potential to address these

Acknowledgments

We acknowledge the Robert L. and Mary Ellenburg Professorship at Stanford University (SBG) and funding from the National Science Foundation (DMR 0846363 to SCH) and the National Institutes of Health (U19 AI116484–01, R21 EB018407–01, R21 AR062359-01 to SCH).

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