Titanium (Ti) and its alloys are believed to be promising scaffold materials for dental and orthopedic implantation due to their ideal mechanical properties and biocompatibility. However, the host immune response always causes implant failures in the clinic. Surface modification of the Ti scaffold is an important factor in this process and has been widely studied to regulate the host immune response and to further promote bone regeneration. In this study, a calcium-strontium-zinc-phosphate (CSZP) coating was fabricated on a Ti implant surface by phosphate chemical conversion (PCC) technique, which modified the surface topography and element constituents. Here, we envisioned an accurate immunomodulation strategy via delivery of interleukin (IL)-4 to promote CSZP-mediated bone regeneration. IL-4 (0 and 40 ng/mL) was used to regulate immune response of macrophages. The mechanical properties, biocompatibility, osteogenesis, and anti-inflammatory properties were evaluated. The results showed that the CSZP coating exhibited a significant enhancement in surface roughness and hydrophilicity, but no obvious changes in proliferation or apoptosis of bone marrow mesenchymal stem cells (BMMSCs) and macrophages. In vitro, the mRNA and protein expression of osteogenic related factors in BMMSCs cultured on a CSZP coating, such as ALP and OCN, were significantly higher than those on bare Ti. In vivo, there was no enhanced bone formation but increased macrophage type 1 (M1) polarization on the CSZP coating. IL-4 could induce M2 polarization and promote osteogenesis of BMMSCs on CSZP in vivo and in vitro. In conclusion, the CSZP coating is an effective scaffold for BMMSCs osteogenesis, and IL-4 presents the additional advantage of modulating the immune response for bone regeneration on the CSZP coating in vivo.
Zinc (Zn) alloys provide a new generation for orthopedic applications due to their essential physiological effects and promising degradation properties. However, excessive release of Zn ions (Zn2+) during degradation and the severe inflammatory microenvironment are not conducive to osseointegration, which is determined by the characteristics of the implant surface. Therefore, it is essential to modulate the release rate of Zn alloys by surface modification technology and endow them with anti‐inflammatory and osteogenic effects. In this study, two kinds of phosphate chemical conversion (PCC) coatings with different compositions and morphological structures are prepared, namely Zn–P (with disk‐like crystals) and Ca–Zn–P (with lamellar crystals). Although all the PCC‐coated Zn implants have low cytotoxicity, Ca–Zn–P show better osteoimmunomodulation effects in several aspects: the induction of the M2‐phenotype macrophage polarization and thus promotion of osteogenesis in vitro; the regulation of the bone immune microenvironment which is conducive to tissue regeneration and osseointegration in vivo; and the release of ions (through PI3K/AKT and Wnt signaling pathways) and the morphological structures (through RhoGTPase signaling pathways) act as possible mechanisms of M2 polarization. The Ca–Zn–P coating can be considered to provide new insights into bone immunomodulation and osseointegration.
Implant-associated infections (IAI) remains a common and devastating complication in orthopedic surgery. To reduce the incidence of IAI, implants with intrinsic antibacterial activity have been proposed. The surface functionalization and structure optimization of metallic implants can be achieved by surface modification using the phosphate chemical conversion (PCC) technique. Zinc (Zn) has strong antibacterial behavior toward a broad-spectrum of bacteria. Herein, Zn was incorporated into strontium−calcium-phosphate (SrCaP) coatings on titanium (Ti) via PCC method, and the influence of its doping amount on the phase, microstructure, antibacterial activity, and biocompatibility of the composite coating was researched. The results indicated that traces of Zn doping produced grain refinement of SrCaP coating with no significant effect on its phase and surface properties, while a higher Zn content induced its phase and microstructure transformed into zinc−strontium-phosphate (SrZn 2 (PO 4 ) 2 ). SrCaP-Zn1 and SrCaP-Zn4 represented trace and high content Zn-doped coatings, respectively, which exhibited a similar bacterial attachment for a short time but showed inhibition of biofilm formation after continuous incubation up to 24 h. The killing rates of SrCaP-Zn1 coating for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) reached 61.25% and 55.38%, respectively. While that data increased to 83.01% and 71.28% on SrCaP-Zn4 coating due to the more-releasing Zn 2+ . Furthermore, in vitro culture of MC3T3-E1 cells proved that the Zn-doped coatings also possessed excellent biocompatibility. This study provides a new perception for the phase and microstructural optimization of phosphate coatings on implant surfaces, as well as fabricating promising coatings with excellent biocompatibility and antimicrobial properties against IAI.
Periprosthetic joint infection (PJI) is one of the most pivotal issues accounting for clinical failure of titanium (Ti)-based implants. Therefore, it is of great significance to develop an antibacterial coating with high biocompatibility on the Ti implant surface. In this article, a novel zinc-doped strontium phosphate coating, denoted as Sr-Zn-PCC, was deposited on Ti substrates by phosphate chemical conversion (PCC) method. The texture characterizations indicated that continuous coatings containing SrHPO4, Sr3(PO4)2 and SrZn2(PO4)2 phases were formed on the Ti surface. It is found that the doping of Zn could tune the surface microstructure, roughness, wettability and corrosion resistance of the coatings. The Sr-Zn-PCC coating showed the same bacterial adhesion property at short time (2 h), but tended to hinder biofilm formation on coatings after incubation for up to 24 h. Up to 80% of Staphylococcus aureus (S. aureus) were killed within 24 h by contact with the Sr-Zn-PCC surface. Moreover, cytocompatibility assay indicated that MC-3T3 cells had good adhesion, spreading properties on the coatings, suggesting that it is a promising alloy with both excellent antibacterial ability and high biocompatibility for the applications on orthopedic implants.
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