Optimizing interactions between biomaterials and hard tissue (orthopedic & dental)

Metals and metallic alloys are widely used in biomedical applications especially for load bearing and hard tissue prosthesis. Titanium and its alloys are well-established biomaterials for dental and orthopedic implants due to their excellent mechanical strength, light-weight, biocompatibility and corrosion resistance. However, the surface of titanium alloys is bioinert, which limits their potential in promising osteogenesis and osseointegration[40]. Recent advances in surface engineering of titanium alloys mainly focus on improving the bioactive interactions between implants and host bones through nanoscale functional coatings such as titanium oxide layer and bioactive calcium phosphate deposition.
Microarc oxidation (MAO) can produce porous titanium oxide coating on metallic implants. A novel hierarchical implant surface with micro/nanomorphology was developed by a duplex coating process. A titanium oxide layer was first generated by MAO, and then the coating was electrochemically reduced in alkaline solution (MAO-AK)[41]. Such modified titanium promoted adhesion and proliferation of seeded canine bone marrow stem cells. Besides, those stem cells were guided towards osteogenic differentiation by MAO-AK modified titanium. As implanted into canine femurs for 10 weeks, accelerated bone formation and higher bone-implant contact ratio were noticed in MAO-AK treated titanium compared to MAO only treated implants. Yang and Huang developed multiform TiO2nano-network coated titanium implants through a simple electrochemical anodization process[42]. The pore size in this TiO2 coating ranged from a few nanometers to a few hundreds of nanometers, which provided a large number of cell adhesion sites for the formation of focal adhesion complex. Such surface modified titanium implants promoted the osteogenic differentiation of human bone marrow hMSCs.
Different oxidizing atmosphere of titanium implants can result in surface deposition composed of various phases. It was investigated that surface oxidization of titanium in air leading to the rutile bioactive phase (TiO2) deposition. In contrast, under pure oxygen atmosphere, titanium monoxide (TiO) also formed on the surface besides TiO2[43]. High concentration of oxygen in pure oxygen atmosphere may induce a rapid oxidation process, thus forming an oxide layer on the surface which inhibits further oxidation. On the contrary, less oxygen in air allows more diffusion of oxygen across the titanium surface which leading to a gradual and sufficient titanium oxidation process. Different atmosphere treatments showed no significant effects on surface topography. Whereas the hydrophilicity of air-treated surface was significantly higher than that treated by pure oxygen. Similarly, air-treated implants were more efficient in apatite forming, cell attachment and proliferation, which suggests that air is more promising for the titanium implants oxidation compared with pure oxygen for better biofunctionalization outcomes.
Jeong et al. studied the effects of nonthermal atmospheric pressure plasma treatment (NTAPP)-treated titanium dental implant surface on oral soft tissue integration and control of cytokine release[44]. The inflammatory cytokine release is essential to physiological functions; however, overproduction may cause the destruction of surrounding soft tissue. The topographic features of titanium surface were not altered due to NTAPP treatment, whereas higher hydrophilicity and surface energy were detected. Inflamed cells on NTAPP-treated samples exhibited lower cytokine release compared with those seeded on untreated implants. However, higher cytokine level of inflamed cells was observed when compared with normal cells on NTAPP-treated implants. Which suggests that such surface engineered titanium implants may control the cytokine release necessary for proper inflammation response instead of a complete reduction in cytokine release.
Hydroxyapatite (HA) as an example of calcium phosphate, is an osteoconductive biomaterial that closely resembles the mineral phase in native bones[45]. HA coatings have been used for fixation of titanium hip replacements for over 20 years. Recent research focuses on adopting HA as a base layer and incorporating other functional molecules for diverse functions such as healing acceleration and infection reduction. Sarkar and Bose coated titanium implants (Ti6Al4V) with HA via plasma spraying to achieve better osseointegration for load-bearing bone-defect repair after osteosarcoma resection[46]. Plasma spraying is the most common method to apply HA coating that creates a rough and porous microstructure benefiting bone fixation. Besides, a localized dual-drug delivery system was constructed by applying curcumin and vitamin K2 on the surface of coated implants through simple physical adsorption for postoperative chemoprevention. The surface roughness was significantly increased upon HA deposition. The drug included HA-coated implants showed excellent performance in inhibiting in vitro osteosarcoma cell proliferation, which indicates their chemopreventive effect. That could address the difficulty in bone regeneration in tumor environment and prevent tumor recurrence. To assess the in vivoosseointegration ability, drug releasing HA-coated titanium implants were inserted in distal femur of rats. Dual-drug incorporated implants showed prominently improved bone-implant integration compared to HA only coated implants. Combining localized drug delivery with enhanced biocompatible titanium implants is effective for repairing tumor-associated bone defects.
Engineering of titanium implants with TiO2 nanotubes can improve surface chemistry and hydrophilicity, hence better cell attachment. However, the bioactivity brought by such nanoscale surface modification is reported to be insufficient compared to calcium phosphate (CaP) coating[47]. And in some cases, CaP coating encounters low adhesion strength to substrates and occasional in vivo delamination problems. Bose et al.applied strontium ions and silicon ions doped calcium phosphate coating on TiO2 nanotubes modified porous titanium implants by biomimetic coating[48]. The TiO2 nanotubes were first fabricated onto the titanium surface via electrochemical anodization. The surface modified metallic implants were immersed in SBF solutions at physiologic temperature and pH to grow homogenous CaP apatite layer on the surface. Histological evaluation showed evident and more osteoid formation and tissue ingrowth at the interface of CaP/ TiO2 coated Ti implants than Ti implants with nanotubes alone. Such effects were more pronounced in early healing stage (4 weeks). Push out tests after 4-weeks implantation showed a higher shear modulus of CaP/ TiO2 coated implants than TiO2 alone coated ones (80 MPa v.s 26 MPa), which reveals a better tissue adherence and mechanical interlocking.
Besides the dual-coating of TiO2 nanotubes and CaP onto titanium implants, there was a nanocomposite coating developed and applied to Ti6Al4V aiming for better corrosion resistance and osseointegration[49]. A PMMA-silica hybrid coating was synthesized by radical polymerization and deposited on Ti6Al4V by dip-coating. The PMMA-silica coated titanium implant presented a homogenous, relatively smooth and crack free surface with a roughness value of 1.3 ± 0.1 nm. The silica addition not only significantly increased the coating adhesion to the substrate, but contributed to notable improvement in coating durability (> 100 days). As stated by authors, the PMMA-silica treated titanium implants exhibited an anticorrosive performance that are superior to other reported anticorrosion coating on Ti6Al4V implants, for instances, SiO2-HA coating and PCL-HA coating.
The main cause of failure in joint replacements is implant loosening due to the inflammation response induced by wear debris (Figure 4). A thin layer of polyamide was coated on UHMWPE to strength the surface for reduction in wear debris[50]. The polyamide coated UHMWPE showed significantly higher antibacterial property than uncoated implants as well as enhanced wound healing effect. CoCrMo alloys are mostly used in join replacement due to their relatively high corrosion resistance and optimal mechanical properties. To improve their tribology performance, more wear-resistant materials can be coated on the bearing surface. Lohberger et al. studied the biological effects of ceramic surface coating on CoCrMo alloys[51]. A 5.5 ± 1.5 µm thick TiN layer was deposited on CoCrMo alloys using physical vapor deposition. The TiN coating was considered to be anti-allergic, wear-reducing and biocompatible coating. Releasing of particles and metal ions due to corrosion and abrasion was reduced through the TiN coating. Human osteoblasts seeded on TiN coated alloys exhibited improved cell viability and adhesion properties.