Infection burden and immunological responses are equivalent for polymeric and metallic implant materials in vitro and in a murine model of fracture‐related infection

Abstract

The development of an infection is a major complication for some patients with implanted biomaterials. Whether the material or surface composition of the used biomaterial influences infection has not been directly compared for key biomaterials currently in use in human patients. We conducted a thorough in vitro and in vivo investigation using titanium (Ti) and polyether-ether-ketone (PEEK) as both commercially available and as modified equivalents (surface polished Ti, and oxygen plasma treated PEEK). Complement activation and cytokine secretion of cell of the immune system was assessed in vitro for all materials in the absence and presence of bacterial stimulants. In a follow-up in vivo study, we monitored bacterial infection associated with clinically available and standard Ti and PEEK inoculated with Staphylococcus aureus. Complement activation was affected by material choice in the absence of bacterial stimulation, although the material based differences were largely lost upon bacterial stimulation. In the in vivo study, the bacterial burden, histological response and cytokine secretion suggests that there is no significant difference between both PEEK and Ti. In conclusion, the underlying material has a certain impact in the absence of bacterial stimulation, however, in the presence of bacterial stimulation, bacteria seem to dictate the responses in a manner that overshadows the influence of material surface properties.

Longitudinal time-lapse in vivo micro-CT reveals differential patterns of peri-implant bone changes after subclinical bacterial infection in a rat model

“…In the present iteration of the model, barium sulfate-enhanced PEEK gives good image quality and image processing is easily automated, making the model suitable for longitudinal studies. The use of PEEK also has clinical relevance, since it is increasingly used in orthopedic medicine and we have shown that the progression of infection around PEEK devices is essentially identical to titanium in a mouse model 23 . Using this model, non-infected rats display an uninterrupted progression of implant integration and bone remodeling, peak bone formation at day 14, and minimal periosteal reaction.…”

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

“…179 Once implanted, a bacterial culture is inoculated into the intraarticular space near the implant. 173 Implant-associated infection models have been established using a range of bacteria including Staphylococcus aureus and methicillinresistant S. aureus (MRSA), [32][33][34]36,115,117,128,134,[169][170][171][172][173][174][175][176][177][178][179][180][181][182]184,185 Staphylococcus epidermidis, 116 Escherichia coli, 163,180 Pseudomonas aeruginosa, 163 Propionibacterium acnes, 116,183 and Streptococcus agalactiae. 172 Bioluminescent strains of bacteria (e.g., S. aureus, E. coli) are frequently used to enable in vivo tracking and imaging of the extent and evolution of the infection over time.…”

“…32,34,179,185 To measure and track the extent of the infection during and at the end of the study, in vivo bioluminescence imaging (BLI) of bacteria and colony forming unit (CFU) counts in excised bone and synovial tissue and on r e m o v e d i m p l a n t s h a v e b e e n a n alyzed. 12,32,33,36,[115][116][117]128,134,163,[170][171][172][173][174][175][176][177][178][179]182,183,185 Histology (e.g., hematoxylin and eosin, Gram stain, tartrate-resistant acid phosphatase (TRAP)) is performed on excised bone and synovial tissue to supplement CFU counts and to identify osteoclasts. 12,32,36,115,117,128,163,[169][170][171][172]174,[176][177][178][179]182,183,185 Scanning electron microscopy (SEM) and crystal violet staining are used to ...…”

“…12,32,33,36,[115][116][117]128,134,163,[170][171][172][173][174][175][176][177][178][179]182,183,185 Histology (e.g., hematoxylin and eosin, Gram stain, tartrate-resistant acid phosphatase (TRAP)) is performed on excised bone and synovial tissue to supplement CFU counts and to identify osteoclasts. 12,32,36,115,117,128,163,[169][170][171][172]174,[176][177][178][179]182,183,185 Scanning electron microscopy (SEM) and crystal violet staining are used to further examine the architecture and presence of bacterial biofilm on the excised implant. 32,170,173,175,181 Radioactive tracers (e.g., 18 ...…”

“…Nondegradable polymeric materials such as poly­(ether ether ketone), ,− poly­(ethylene glycol) (PEG), − ,,, poly­(ethyleneimine), , cyclodextrin, ,− poly­(methyl methacrylate) (PMMA), ,,,,,− polyethylene terephthalate, , silicone, , and polyesters , have the potential to serve as long-term antimicrobial materials. Since the release of antibiotics from nondegradable materials is not associated with the rate of degradation of the material, these materials primarily rely on diffusion and affinity-based interactions to dictate the release kinetics of antibiotics.…”