Biomechanical and histomorphometric evaluation of skin integration on titanium and PEEK implants with different surface treatments.

Percutaneous implants are frequently affected by bacterial growth at the skin-implant interface. Integration between implant and surrounding skin is important to prevent bacteria from spreading to the underlying tissue. The standard method to evaluate skin-implant integration is by histomorphometry on samples which have been placed in tissue grown in vivo or ex vivo. In this study, a biomechanical method was developed and evaluated. The integration of implants into porcine skin was studied in an ex vivo model, where pig skin samples were cultivated in a nutrient solution. Cylindrical shaped implants, consisting of polyether ether ketone (PEEK) and titanium (Ti) with different surface treatments, were implanted in the skin tissue and the skin was grown in nutrient solution for 2 weeks. The implants were then extracted from the implantation site and the mechanical force during extraction was measured as a quantitative assessment of skin-implant integration. Implants from each group were also processed for histomorphometry and the degree of epidermal downgrowth (ED) and tissue to implant contact (TIC) was measured. A higher mean pullout force was observed for the PEEK implants compared to the Ti implants. Applying nanosized hydroxyapatite (HA) on Ti and PEEK increased the pullout force compared to uncoated controls, 24% for machined and 70% for blasted Ti, and 51% for machined PEEK. Treatment of Ti and PEEK with nanosized zirconium phosphate (ZrP) did not increase the pullout force. The histomorphometry analysis showed correlation between ED and pullout force, where the pullout force was inversely proportional to ED. For TIC, no significant differences were observed between the groups of same material (i.e. Ti, Ti+HA, Ti+ZrP, and PEEK, PEEK + HA, PEEK + ZrP), but it was significantly higher for PEEK compared to Ti. Scanning electron microscopy analysis was done on samples before and after the pullout tests, showing that the ZrP coating was unaffected by the 2 week ex vivo implantation and pullout procedure, no dissolution or detachment of the coating was observed. For the HA coating, a loss of coating was seen on approximately 5% of the total surface area of the implant. Graphical abstract.

Surface immobilized zoledronate improves screw fixation in rat bone: a new method for the coating of metal implants.

Previous studies show that surface immobilized bisphosphonates improve the fixation of stainless steel screws in rat tibia after 2-8 weeks of implantation. We report here about the immobilization of a potent bisphosphonate, zoledronate, to crosslinked fibrinogen by the use of another technique, i.e. ethyl-dimethyl-aminopropylcarbodiimide (EDC)/imidazole immobilization. Bone fixation of zoledronate-coated screws was compared to screws coated with crosslinked fibrinogen only and ditto with EDC/N-hydroxy-succinimide immobilized pamidronate. Fixation in rat tibia was evaluated by a pull-out test at either 2 or 6 weeks after implantation. Both bisphosphonate coatings increased the pull-out force at both time points, and zoledronate showed a significantly higher pull-out force than pamidronate. To further evaluate the new coating technique we also performed a morphometric study, focusing on the area surrounding the implant. The zoledronate coating resulted in an increased bone density around the screws compared to controls. No pronounced increase was seen around the pamidronate coated screws. Together, the results demonstrate the possibility of obtaining a significant local therapeutic effect with minute amounts of surface immobilized zoledronate.

Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings.

A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged ß-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

Characterization of the in vitro, ex vivo, and in vivo Efficacy of the Antimicrobial Peptide DPK-060 Used for Topical Treatment.

Antimicrobial peptides, also known as host defense peptides, have recently emerged as a promising new category of therapeutic agents for the treatment of infectious diseases. This study evaluated the preclinical in vitro, ex vivo, and in vivo antimicrobial activity, as well as the potential to cause skin irritation, of human kininogen-derived antimicrobial peptide DPK-060 in different formulations designed for topical delivery. We found that DPK-060 formulated in acetate buffer or poloxamer gel caused a marked reduction of bacterial counts of Staphylococcus aureus in vitro (minimum microbicidal concentration <5 µg/ml). We also found that DPK-060 in poloxamer gel significantly suppressed microbial survival in an ex vivo wound infection model using pig skin and in an in vivo mouse model of surgical site infection (≥99 or ≥94% reduction in bacterial counts was achieved with 1% DPK-060 at 4 h post-treatment, respectively). Encapsulation of DPK-060 in different types of lipid nanocapsules or cubosomes did not improve the bactericidal potential of the peptide under the applied test conditions. No reduction in cell viability was observed in response to administration of DPK-060 in any of the formulations tested. In conclusion, the present study confirms that DPK-060 has the potential to be an effective and safe drug candidate for the topical treatment of microbial infections; however, adsorption of the peptide to nanocarriers failed to show any additional benefits.