CORR Insights®: Vitamin E Phosphate Coating Stimulates Bone Deposition in Implant-related Infections in a Rat Model

Where Are We Now?

Implant materials have a high risk of infection due to biofilm formation on certain surfaces [4], which can also trigger inflammatory reactions that lead to osteonecrosis, implant loosening, and revision surgery. Implant coatings have been designed to either prevent infection, improve osseointegration, or both [6]. Absorbable or nonabsorbable implant coatings may serve as local-delivery systems when combined with therapeutics such as proteins or antibiotics.

The current study by Lovati and colleagues [7] elucidates a strategy for implant coatings to modulate the inflammatory response to prevent infection-induced bone loss. Building on the reported antibacterial effects of vitamin E and its phosphate esters [1], vitamin E phosphate coatings formed by a simple immersion process have been shown to be antiadhesive to bacteria, which could prevent bacterial biofilm formation [2]. The anti-inflammatory properties of orally ingested vitamin E are well known and could prevent bone destruction by bacteria [3].

The findings in the current study indicate that vitamin E phosphate-coated implants reduced the risk of osteonecrosis with implant-associated infection, though the antimicrobial properties of vitamin E phosphate alone did not considerably impact bacterial colonization of bone [7]. Fewer signs of infection were observed in coated implants in this highly contaminated model, although no antibacterial effects were detected.

In their study, Lovati and colleagues [7] also include a highly contaminated model of osteomyelitis that has limited applicability to clinical scenarios. Without concurrent antibiotic prophylaxis, the vitamin E phosphate effect in reducing clinical signs of infection may actually serve to delay diagnosis and intervention for implant-associated infection. The authors also suggest that the vitamin E phosphate coatings could be combined with antibiotics to serve as a local delivery system [7], but without an antimicrobial therapy to eradicate bacterial biofilm, the infection and accompanying tissue destruction would still occur as the vitamin E phosphate within the coating is depleted.

Where Do We Need To Go?

Despite the findings in the current study, gaps in our knowledge remain regarding how the mechanisms of vitamin E protect from bone loss. In fact, some studies provide conflicting evidence about the benefits of vitamin E in bone [5, 9]. Oral supplementation of vitamin E shows no association with changes in bone mineral density [8]. The local-delivery strategy in the investigated coating has potential to target tissue directly, and may provide an added benefit over oral supplementation with vitamin E. While no cytotoxic or inflammatory reactions were noted in the current study, dose-response studies (particularly for implants of various sizes and geometries) would be a critical element in bringing this coating into routine clinical use.

The retention of the implant coating after the dip-coating procedure was not evaluated in this study [7], which had only a 6-week surveillance period. The adsorption of coatings onto titanium has been demonstrated in previous research [2], but studies examining this coating procedure on other implant materials could expand its clinical applicability. Further, the ability of the coatings to withstand implantation procedures, mechanical loads, and high temperatures associated with bone cement is unknown. But Lovati and colleagues [7] do indicate that longer-lasting coatings are in development, which could provide longer-term protection of implants.

How Do We Get There?

Further preclinical investigations combining the vitamin E coating with systemic antibiotic administration in accordance with contemporary clinical guidelines should precede clinical investigations into this novel coating technique. Future studies should characterize various antibiotics in combination with the system, as well as release profile and possible additive, synergistic, or antagonistic effects of a vitamin/antibiotic combination. Inclusion of different time points prior to 6 weeks and beyond 42 days could advance the clinical potential of this and similar coatings.

Thorough materials characterization is also needed to determine how much vitamin E is adsorbed to the surface, how it is released, and how long the coating remains active. Mechanistic studies of vitamin coatings would also support this promising strategy for improving osseointegration when used in conjunction with infection preventative therapeutics.