No abstract

In the last 5 years, a wide variety of surface modification strategies are explored to improve the integration of poly(etheretherketone) (PEEK) implants with bone. Since PEEK does not support bone on‐growth, its surface properties need to be tailored to promote osteogenesis at the bone‐implant interface. Surface modifications applied to achieve this response range from simple surface morphology changes to the deposition of osteoconductive coatings. Of the many methods, titanium and/or hydroxyapatite coatings, extrusion to create surface pores, and an accelerated neutral atom beam treatment have been approved by the U.S. Food and Drug Administration to improve the integration of PEEK spinal cages. The success of these surface modifications brings hope for the clinical translation of other techniques in the future, but there are several limitations that may be preventing other treatments from reaching the clinic. This review describes numerous strategies that have been applied to PEEK‐based implants for improving their osseointegration and enhancing their antibacterial properties. The review concludes with a discussion about future directions for the field and provides suggestions for advancing clinical translation of surface‐modified PEEK implants to improve the lives of patients in need of these implants.

Implants can induce a foreign body reaction that leads to chronic inflammation and fibrosis in the surrounding tissue. Macrophages help detect the foreign material, play a role in the inflammatory response, and may promote fibrosis instead of the desired tissue regeneration around implants. Implant surface properties impact macrophage responses by changing the nature of the adsorbed protein layer, but conflicting studies highlight the complexity of this relationship. In this study, the effect of surface chemistry on macrophage behavior was investigated with poly­(styrene) surfaces containing common functional groups at similar surface densities. The protein layer was characterized to identify the proteins that adsorbed on the surfaces from the medium and the proteins secreted onto the surfaces by adherent macrophages. Of the surface chemistries studied, carboxylic acid (COOH) groups promoted anti-inflammatory responses from unstimulated macrophages and did not exacerbate inflammation upon stimulation. These surfaces also enhanced the adsorption of proteins involved in integrin signaling and promoted the secretion of proteins related to angiogenesis, integrin signaling, and cytokine signaling, which have been previously associated with improved biomaterial integration. Therefore, this study suggests that surface modification with COOH groups may help improve the integration of implants in the body by enhancing anti-inflammatory macrophage responses through altered protein adsorption.

Electrospun fibers are excellent candidates for wound dressings and tissue engineering scaffolds. To actively prevent infection during wound healing, the electrospun fibers can be loaded with antimicrobial agents, such as antibiotics or natural antimicrobials. Different methods have been used to incorporate antimicrobial agents in electrospun fibers during the electrospinning process, including blending, coaxial electrospinning, and emulsion electrospinning, to provide controlled release of the agent. Some evidence suggests that a burst release of antimicrobials through physical adsorption, or physisorption, may offer improved antibacterial properties, but a comparison between physisorbed and blended antimicrobial agents has not been conducted. In this study, the antimicrobial and release properties of poly(lactide-co-glycolide) electrospun fibers containing either blended or physisorbed ciprofloxacin are compared using disks containing similar initial amounts of ciprofloxacin. The results demonstrate that physically adsorbed ciprofloxacin provides more effective antibacterial properties than blended ciprofloxacin up to 48 h against P. aeruginosa PA14, S. aureus, and S. epidermidis regardless of initial loading due to a faster release of the antibiotic in the first 6 h. However, beyond 24 h, blended ciprofloxacin retained the clear zones better than physisorbed ciprofloxacin due to a continuous release. Physisorption offers a simple approach for incorporating antibiotics in electrospun fibers for stronger short-term antibacterial effects and may be applied to scaffolds containing blended antibiotics to sustain antibacterial properties for long-term wound dressings.

Poly(etheretherketone) (PEEK) implants suffer from poor osseointegration because of chronic inflammation. In this study, we hypothesized that adding NH 2 and COOH groups to the surface of PEEK could modulate macrophage responses by altering protein adsorption and improve its osseointegration. NH 2 and COOHfunctionalized PEEK surfaces induced pro-and anti-inflammatory macrophage responses, respectively, and differences in protein adsorption patterns on these surfaces were related to the varied inflammatory responses. The macrophage responses to NH 2 surfaces significantly reduced the osteogenic differentiation of mesenchymal stem cells (MSCs). MSCs cultured on NH 2 surfaces differentiated less than those on COOH surfaces even though NH 2 surfaces promoted the most mineralization in simulated body fluid solutions. After 14 days in rat tibia unicortical defects, the bone around NH 2 surfaces had thinner trabeculae and higher specific bone surface than the bone around unmodified implants; surprisingly, the NH 2 implants significantly increased bone-binding over the unmodified implants, while COOH implants only showed a trend for increasing bone-binding. Taken together, these results suggest that both mineral-binding and immune responses play a role in osseointegration, and PEEK implant integration may be improved with mixtures of these two functional groups to harness the ability to reduce inflammation and bind bone strongly.