Engineered porous scaffolds for periprosthetic infection prevention.

Periprosthetic infection is a consequence of implant insertion procedures and strategies for its prevention involve either an increase in the rate of new bone formation or the release of antibiotics such as vancomycin. In this work we combined both strategies and developed a novel, multifunctional three-dimensional porous scaffold that was produced using hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP), coupled with a pectin (PEC)-chitosan (CHIT) polyelectrolyte (PEI), and loaded with vancomycin (VCA). By this approach, a controlled vancomycin release was achieved and serial bacterial dilution test demonstrated that, after 1week, the engineered construct still inhibits the bacterial growth. Degradation tests show an excellent behavior in a physiological and acidic environment (<10% of mass loss). Furthermore, the PEI coating shows an anti-inflammatory response, and good cell proliferation and migration were demonstrated in vitro using osteoblast SAOS-2 cell line. This new engineered construct exhibits excellent properties both as an antibacterial material and as a stimulator of bone formation, which makes it a good candidate to contrast periprosthetic infection.

In Vitro Cytokine Expression and In Vivo Healing and Inflammatory Response to a Collagen-Coated Synthetic Bone Filler.

The goal of the present work was to investigate the relationship between in vivo healing and inflammatory response and in vitro cytokine expression by macrophages of a synthetic bone filler (25% hydroxylapatite-75% ß-tricalcium phosphate) bearing a surface nanolayer of collagen. A clinically accepted, state-of-the-art xenograft material was used as a "negative control," that is, as a material that provides the correct clinical response for the intended use. In vitro data show that both materials exert a very low stimulation of proinflammatory cytokines by macrophages, and this was confirmed by the very mild inflammatory response detected in in vivo tests of local response in a rabbit model. Also, in vitro findings suggest a different mechanism of healing for the test and the control material, with a higher regenerative activity for the synthetic, resorbable filler, as confirmed by in vivo observation and literature reports. Thus, the simple in vitro model adopted provides a reasonable forecast of in vivo results, suggesting that new product development can be guided by in vitro tuning of cell-materials interactions.

Collagen type I coating stimulates bone regeneration and osteointegration of titanium implants in the osteopenic rat.

PURPOSE: To investigate the effects of titanium implants functionalised with collagen type I (TiColl) on bone regeneration and osteointegration in a healthy and osteopenic rat animal model. METHOD: TiColl screws were implanted into the femoral condyles of healthy and osteopenic rats and compared with acid-etched titanium (Ti) screws. The osteointegration process was evaluated by a complementary approach combining microtomographic, histological, histomorphometric and biomechanical investigations at four and 12 weeks. RESULTS: The TiColl screw also ensured a greater mechanical stability; the push-out values for TiColl screws increased from four to 12 weeks (+28 %). The energy necessary to detach the bone from the screw was significantly higher for TiColl-functionalised screws in comparison to Ti screws (+23 %) at 12 weeks. Histomorphometric investigation revealed that total bone-to-implant contact was higher in TiColl screws in comparison to Ti screws (P < 0.05) and at epiphyseal level, increased bone-to-implant contact was found with TiColl screws in comparison to Ti screws (P < 0.05) in an ovariectomy (OVX) condition. A significant increase in the measured total bone ingrowth from four to 12 weeks was detected for both materials, but more significant for the TiColl material (P < 0.0005). Finally, bone ingrowth in the TiColl group was significantly higher (P < 0.005) in comparison to that of Ti screws in the SHAM condition at metaphyseal level at 12 weeks. CONCLUSION: The present results showed that TiColl is effective in promoting implant osteointegration even in compromised bone.

Surface chemistry and effects on bone regeneration of a novel biomimetic synthetic bone filler.

The paper presents results of physico-chemical and biological investigations of a surface-engineered synthetic bone filler. Surface analysis confirms that the ceramic phosphate granules present a collagen nanolayer to the surrounding environment. Cell cultures tests show that, in agreement with literature reports, surface-immobilized collagen molecular cues can stimulate progression along the osteogenic pathway of undifferentiated human mesenchymal cells. Finally, in vivo test in a rabbit model of critical bone defects shows statistically significant increase of bone volume and mineral apposition rate between the biomimetic bone filler and collagen-free control. All together, obtained data confirm that biomolecular surface engineering can upgrade the properties of implant device, by promoting more specific and targeted implant-host cells interactions.

Adherent endotoxin on dental implant surfaces: a reappraisal.

Osteoimmunology is the crosstalk between cells from the immune and skeletal systems, suggesting a role of pro-inflammatory cytokines in the stimulation of osteoclast activity. Endotoxin or bacterial challenges to inflammatory cells are directly relevant to dental implant pathologies involving bone resorption, such as osseointegration failure and peri-implantitis. While the endotoxin amount on implant devices is regulated by standards, it is unknown whether commercially available dental implants elicit different levels of adherent-endotoxin stimulated cytokines. The objective of this work is to develop a model system and evaluate endotoxin-induced expression of pro-inflammatory cytokine genes relevant to osteoclast activation on commercially available dental implants. Murine J774-A1 macrophages were cultured on Ti disks with different level of lipopolysaccharide (LPS) contamination to define the time-course of the inflammatory response to endotoxin, as evaluated by reverse transcription polymerase chain reaction analysis. The developed protocol was then used to measure adherent endotoxin on commercially available packaged and sterile dental implants in the "as-implanted" condition. Results show that tested dental implants induce variable expression of endotoxin-stimulated genes, sometimes above the level expected to promote bone resorption in vivo. Results are unaffected by the specific surface treatment; rather, they likely reflect care in cleaning and packaging protocols. In conclusion, expression of genes that enhance osteoclast activity through endotoxin stimulation of inflammatory cells is widely different on commercially available dental implants. A reappraisal of the clinical impact of adherent endotoxins on dental (and bone) implant devices is required in light of increasing knowledge on crosstalk between cells from the immune and skeletal systems.