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.