The influence of implant geometry and surface composition on bone response.

OBJECTIVES: The implant design and surface modification are independent conditions that can alter the implant bone response. The objective of this study is to compare the bone response to roughened tapered and cylindrical screw-type implants with and without hydroxyapatite (HA) surface coating in the femoral trabecular bone of rabbits. MATERIAL AND METHOD: Thirty-two implants (8 × 3.5 mm) consisting of four different types (eight implants in each group), that is, tapered implants, cylindrical implants, HA-coated tapered implants, and HA-coated cylindrical implants were installed in the femoral condyle of 16 rabbits. After 8 weeks of healing, the femoral condyles were retrieved and studied histologically. The bone-to-implant contact percentage was assessed and analyzed statistically. RESULTS: The histomorphometric analysis revealed that the bone-to-implant contact (BIC) values seemed to be higher for HA-coated tapered implants (65.62 ± 13.02) followed by cylindrical non-coated implants. All four types of implants showed wide distribution of BIC with no statistical significance between different types of implants. CONCLUSION: It can be concluded that under the current experimental conditions, implant design and surface composition had little effect on the bone-to-implant interface.

In situ growth of Ca-Zn-P coatings on the Zn-pretreated WE43 Mg alloy to mitigate corrosion and enhance cytocompatibility.

Magnesium (Mg) alloys are potential materials for orthopedic fixation devices but rapid degradation of the materials restricts wider clinical applications. Herein, zinc-incorporated calcium phosphate (Ca-Zn-P) coatings are prepared on the Zn-pretreated WE43 Mg alloy by a hydrothermal technique under relatively stable and favorable conditions. The hydrothermal coating consists of a compact bottom layer of CaZn2(PO4)2∙2 H2O and ZnO granular crystals and a jagged upper layer of CaHPO4. The Zn coating reduces the corrosion current density of WE43 to (3.49 ± 1.60) × 10-5 A cm-2, whereas the Ca-Zn-P/Zn composite coating further reduces it by 3 orders of magnitude in the simulated body fluid (SBF). The charge transfer resistances of the Zn-coated and Ca-Zn-P/Zn-coated alloys increase by 49 and 7176 times to 835 and 1.22 × 105 Ω cm2, respectively. The 7-day immersion results reveal that the Zn coating cannot provide long-term protection to WE43 in SBF because of the formation of galvanic couples between the Zn coating and WE43. In contrast, Ca-Zn-P/Zn-coated WE43 remains intact after soaking for 7 days and furthermore, the Ca-Zn-P coating self-repairs and continues to grow despite dissolution. The compact and adherent Ca-Zn-P bottom layer plays a major role in mitigating corrosion of WE43 by hindering penetration of the aggressive medium and charge transfer of the corrosion reactions resulting in only slight corrosion of the Zn layer. Biologically, the Zn coating reduces attachment and proliferation of MC3T3-E1 pre-osteoblasts on WE43, but the composite coating fosters cell adhesion and proliferation which stems from the good biocompatibility of the hydrothermal layer and relatively stable surface conditions avoiding severe corrosion.

Amorphous Precursor-Mediated Calcium Phosphate Coatings with Tunable Microstructures for Customized Bone Implants.

Calcium phosphate (CaP) is frequently used as coating for bone implants to promote osseointegration. However, commercial CaP coatings via plasma spraying display similar microstructures, and thus fail to provide specific implants according to different surgical conditions or skeletal bone sites. Herein, inspired by the formation of natural biominerals with various morphologies mediated by amorphous precursors, CaP coatings with tunable microstructures mediated by an amorphous metastable phase are fabricated. The microstructures of the coatings are precisely controlled by both polyaspartic acid and Mg2+ . The cell biological behaviors, including alkaline phosphatase activity, mineralization, and osteogenesis-related genes expression, on the CaP coatings with different microstructures, exhibit significant differences. Furthermore, in vivo experiments demonstrate the osseointegration in different types of rats and bones indeed favors different CaP coatings. This biomimetic strategy can be used to fabricate customized bone implants that can meet the specific requirements of various surgery conditions.

A systematic review on the effect of inorganic surface coatings in large animal models and meta-analysis on tricalcium phosphate and hydroxyapatite on periimplant bone formation.

The aim of the present systematic review was to analyse studies using inorganic implant coatings and, in a meta-analysis, the effect of specifically tricalcium phosphate (TCP) and hydroxyapatite (HA) implant surface coatings on bone formation according to the PRISMA criteria. Inclusion criteria were the comparison to rough surfaced titanium implants in large animal studies at different time points of healing. Forty studies met the inclusion criteria for the systematic review. Fifteen of these analyzed the bone-to-implant contact (BIC) around the most investigated inorganic titanium implant coatings, namely TCP and HA, and were included in the meta-analysis. The results of the TCP group show after 14 days a BIC being 3.48% points lower compared with the reference surface. This difference in BIC decreases to 0.85% points after 21-28 days. After 42-84 days, the difference in BIC of 13.79% points is in favor of the TCP-coatings. However, the results are not statistically significant, in part due to the fact that the variability between the studies increased over time. The results of the HA group show a significant difference in mean BIC of 6.94% points after 14 days in favor of the reference surface. After 21-28 days and 42-84 days the difference in BIC is slightly in favor of the test group with 1.53% points and 1.57% points, respectively, lacking significance. In large animals, there does not seem to be much effect of TCP-coated or HA-coated implants over uncoated rough titanium implants in the short term.

Effects of composition and hierarchical structures of calcium phosphate coating on the corrosion resistance and osteoblast compatibility of Mg alloys.

Magnesium and its alloys have been recently used in biomedical applications such as orthopedic implants, whereas the weak corrosion resistance undermines their clinical efficacy. Herein, to address this critical challenge, the preparation of hierarchically structured hydroxyapatite-based coatings was proposed. Compact coatings were fabricated on a Mg alloy through a facile two-step method of chemical deposition of brushite precursor and subsequent hydrothermal conversion. A series of HA-based coatings were obtained with kinetic conversion process with formation mechanism revealed. The hydroxyapatite coating demonstrated the greatest corrosion resistance for Mg in electrochemical and long-term immersion tests, especially against pitting corrosion, attributable to its compact structure, alkaline degradation environment and self-induced growth capacity. The in vitro cytocompatibility and osteoinductivity were dictated. Additionally, anti-corrosion mechanisms were compared among different coating compositions and structures, along with their correlation with cellular response. Our study brings hints for a tailored surface design for resorbable biomedical device applications.

Enhanced cytocompatibility and antibacterial property of zinc phosphate coating on biodegradable zinc materials.

Zinc (Zn) has recently emerged as a promising biodegradable metal thanks to its critical physiological roles and promising degradation behavior. However, cytocompatibility and antibacterial property of Zn is still suboptimal, in part, due to the excessive Zn ions released during degradation. Inspired by the calcium phosphate-based minerals in natural bone tissue, zinc phosphate (ZnP) coatings were prepared on pure Zn using a chemical conversion method in this study. The coating morphology was then optimized through controlling the pH of coating solution, resulting in a homogeneous micro-/nano-ZnP coating structure. The ZnP coating significantly increased the cell viability, adhesion, and differentiation of pre-osteoblasts and vascular endothelial cells, while significantly reduced the adhesion of the platelets and E. coli. Additionally, ZnP coating significantly reduced the Zn ion release from the bulk material during degradation process, resulting in a much lower Zn2+ concentration and pH change in the surrounding environment. The improved hemocompatibility, cytocompatibility and antibacterial performance of ZnP coated Zn biomaterials could be mainly attributed to the controlled Zn ion release and micro-/nano-scaled coating structure. Taken together, ZnP coating on Zn-based biomaterial appears to be a viable approach to enhance its biocompatibility and antibacterial property as well as to control its degradation rate. Statement of Significance Zn and its alloys are promising biodegradable implant materials for orthopedic and cardiovascular applications. However, notable cytotoxicity has been reported due to degradation products accumulated in the local environment, largely overdosed Zn2+. Thus, controlling burst Zn2+ release is the key to minimize the toxicity of Zn implants. To achieve this goal, we prepared a homogenous ZnP coating on Zn metals thanks to its easy synthesis, stable chemical property, and good biocompatibility. Results showed that ZnP not only improved the cell viability, adhesion and proliferation, but also significantly reduced the attachment of platelet and bacterial. Therefore, ZnP could be a promising approach to improve the functional performance of Zn-based implants, and potentially be applied to many other medical implants.

Mechanical and biological properties of electrodeposited calcium phosphate coatings.

Calcium phosphate (CaP) coatings were electrochemically deposited on titanium substrates. By increasing the electrodeposition time (from 1 to 30 min), the coating thickness increases but also the surface morphology of the CaP coatings is greatly affected going from smooth to plate-like, featuring elongated plates, ribbon-like and finally sharp needle structures. Micro-stretch tests reveal that, regardless of the coating morphology and thickness, the electrodeposited CaP coatings have strong adhesion with the titanium substrates and their failure mode is cohesive failure. The effects of different morphologies on cellular behavior such as adhesion, viability, proliferation, and osteogenic gene expression were studied. The surface morphology of CaP coatings has a remarkable effect on cell attachment, proliferation, and viability. A smooth surface results in better adhesion of the cells, whereas the presence of sharp needles and ribbons on rough surfaces restricts cell adhesion and consequently cell proliferation and viability. The improved cell adhesion and viability on the smoother surface can be attributed to the higher contact area between the cell and the coating, while the needle-like morphology inflicts damage to the cells by physically disrupting the cell wall. There is no significant difference in the level of osteoblast gene expression when osteosarcoma cells are cultured on coatings with different morphologies. Our study provides crucial insights into the optimum electrodeposition procedures for CaP coating formation leading to both good cell-material interaction and sufficient mechanical properties. This can be achieved with relatively thin coatings produced by short electrodeposition times.

Self-assembling antimicrobial peptides on nanotubular titanium surfaces coated with calcium phosphate for local therapy.

Bacterial infection is a serious medical problem leading to implant failure. The current antibiotic based therapies rise concerns due to bacterial resistance. The family of antimicrobial peptides (AMP) is one of the promising candidates as local therapy agents due to their broad-spectrum activity. Despite AMPs receive increasing attention to treat infection, their effective delivery to the implantation site has been limited. Here, we developed an engineered dual functional peptide which delivers AMP as a biomolecular therapeutic agent onto calcium phosphate (Ca-P) deposited nanotubular titanium surfaces. Dual functionality of the peptide was achieved by combining a hydroxyapatite binding peptide-1 (HABP1) with an AMP using a flexible linker. HABP functionality of the peptide provided a self-coating property onto the nano-topographies that are designed to improve osteointegration capability, while AMP offered an antimicrobial protection onto the implant surface. We successfully deposited calcium phosphate minerals on nanotubular titanium oxide surface using pulse electrochemical deposition (PECD) and characterized the minerals by XRD, FT-IR, FE-SEM. Antimicrobial activity of the engineered peptide was tested against S. mutans (gram- positive) and E. coli (gram-negative) both in solution and on the Ca-P coated nanotubular titanium surface. In solution activity of AMP and dual functional peptide have the same Minimum Inhibitory Concentration (MIC) (32 mg/mL). The peptide also resulted in the reduction of the number of bacteria both for E.coli and S. mutans compare to control groups on the surface. Antimicrobial features of dual functional peptides are strongly correlated with their structures suggesting tunability in design through linkers regions. The dual-function peptide offers single-step solution for implant surface functionalization that could be applicable to any implant surface having different topographies.

Human mesenchymal stromal cells response to biomimetic octacalcium phosphate containing strontium.

The incorporation of bioinorganics into synthetic biomaterials is a promising approach to improve the biological performance of bone graft substitutes, while still retaining their synthetic nature. Among these bioinorganics, strontium ions (Sr(2+) ) have reported enhanced bone formation, and a reduced risk of bone fractures. While previous results have been encouraging, more detailed studies are needed to further develop specific applications. This study demonstrates the effects of Sr(2+) on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) when introduced as either a dissolved salt, or incorporated into biomimetic calcium phosphate (CaP) coatings. Upon attachment, hMSCs seeded in the presence of higher Sr(2+) concentrations presented with a more elongated shape as compared to the controls without Sr(2+) . Both Sr(2+) as a dissolved salt in the medium, or incorporated into CaP coatings, positively influenced hMSC alkaline phosphatase (ALP) activity in a dose-dependent manner. At the mRNA level, the expression of osteogenic markers ALP, bone sialoprotein, bone morphogenetic protein 2, osteopontin, and osteoclacin were increased in the presence of Sr(2+) , independent of the delivery method. Overall, this study demonstrates the positive effects of strontium on the osteogenic differentiation of human MSCs, and supports the use of strontium-incorporated CaPs for bone regeneration applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1946-1960, 2016.

In vivo study of osteogenerating properties of calcium-phosphate coating on titanium alloy Ti-6Al-4V.

The method of formation of bioactive calcium-phosphate coating on medical titanium alloy Ti-6Al-4V (3.5-5.3% V; 5.3-6.8% Al; balance -Ti) by plasma electrolytic oxidation (PEO) has been developed. Evaluation of osteogenerating properties of the coating at fractures of the shaft of the femur on Wistar line laboratory rats has been performed. It has been established that the calcium-phosphate PEO coating accelerates osteogenesis and promotes the formation of a pronounced periosteal callus in the fracture area. The presence of calcium phosphates in the PEO coating surface layer significantly accelerates the growth of bone tissue on the titanium surface.