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Bone growth to metal implants is regulated by their surface chemical properties.

Bony ingrowth to control (non-treated) and heat-treated stainless steel and Ti-6Al-4V implants into the medullary canal of the femur in rats was studied by mechanical, chemical and Auger electron spectroscopic methods. At all time intervals up to 35 d post-implantation, the shear strengths of the heat-treated Ti-6Al-4V and stainless steel implants were significantly higher (1.6-fold to 3.4-fold) than in control implants. Using Auger electron spectroscopy depth profiling methods, it was found that the heat treatment modified the implant surface composition significantly, resulting in a thicker oxide layer and other chemical changes. It is concluded that heat treatment of metal implants prior to their insertion alters their chemical surface properties and augments bony ingrowth to them.

Alloys↗

Bone bonding behavior of the hydroxyapatite containing glass-titanium composite prepared by the Cullet method.

Bioactive composites composed of hydroxyapatite containing glass (HA-G) as a coating and titanium (Ti) or titanium alloy implants as a substrate were prepared by the Cullet method. This method results in the HA-G coating layer on the substrate with a compositional gradient in HA concentration. The results of in vitro and in vivo experiments investigating the characteristics of the composite materials are reported and discussed in this article. In vitro evaluations confirmed that the Cullet method was suitable for the preparation of the functionally gradient composite implants with higher reliable quality. In vivo experiments permitted evaluation of bonding strength of these composite implants to living bone tissue. Mechanical pull-out tests indicated that the implants bonded to living bone at least as firmly as those by the conventional method, and that the adhesion between the HA-G coating layer and metal substrate was well integrated and strongly maintained in vivo. SEM observations with EDX and a histological study of the interface between the HA-G-Ti composite implants and bone tissue revealed not only that the implants bonded to bone directly without any intervening tissue but that bone ingrowth into the HA-G layer occurred. The HA-G-Ti composite implants demonstrate both biocompatible and osteoconductive characteristics, and may be expected to obtain good and lasting results when applied clinically.

Animals↗

Hydroxyapatite-based composite for dental implants: an in vivo removal torque experiment.

Screw-shaped dental implants were fabricated from commercially pure Ti (c.p. Ti) and HA-based composites. The HA-based composites were fabricated by mixing HA with Al(2)O(3)-coated ZrO(2) powders. The mechanical properties of these composites were enhanced by a factor of 3. These were implanted into the rabbit tibiae and the removal torque to loosen the implants in vivo was measured in order to investigate the osteointegration. After a healing period of 6 weeks, the implants were retrieved with a torque gauge instrument. The HA-based composite implants showed an almost 2-times-higher removal torque when compared to the Ti implants (ANOVA, p < 0.05), indicating excellent biocompatibility to bone. Thus, HA-based composites had not only better mechanical properties but also similar bioactivity as HA itself. It is believed that a HA-based composite is suitable for artificial dental implants.

Aluminum Oxide↗

Histological comparison of early wound healing following dense hydroxyapatite granule grafting and barrier placement in surgically-created bone defects neighboring implants.

The purpose of this study was to examine early wound healing following grafting of dense hydroxyapatite granules (HA granules) and barrier placement in surgically-created bone defects surrounding implants. Eight healthy adult dogs with an average weight of 15 kg were used in this study. Thirty-two bone defects measuring 4 mm x 4 mm were removed with a surgical bur to form continuous bucco-lingual bone defects and 32 implants (16 titanium [Ti]) and 16 hydroxyapatite-coated [HA]) were then placed into the defects. Four implant groups were created: 1) grafting HA; 2) covering with an expanded polytetrafluoroethylene (ePTFE) membrane; 3) grafting HA and covering with ePTFE membrane; and 4) control (no treatment). Animals were sacrificed 28 days after surgery. Histological sections revealed large amounts of newly-formed bone in all bone defects surrounding the implants treated with ePTFE membranes alone. Fibrous encapsulation of HA granules was observed in the defects of the HA granules grafting group. In the group with grafting of HA granules and covering with ePTFE membranes, small amounts of bone tissue were observed among HA granules, but most HA granules were surrounded with fibrous tissue. Bone defects were completely filled with connective tissue in the control group. There were no differences in the histological findings between Ti and HA-coated implants in all cases. Histomorphometric data disclosed that the presence of HA granules in the bone defects significantly arrested bone formation. Our study suggests that the grafting of dense HA into bone defects surrounding implants will result in fibrous healing during the early healing stage.

Alveolar Bone Loss↗

Early bone apposition in vivo on plasma-sprayed and electrochemically deposited hydroxyapatite coatings on titanium alloy.

Three different implants, bare Ti-6Al-4V alloy, Ti-6Al-4V alloy coated with plasma-sprayed hydroxyapatite (PSHA), and Ti-6Al-4V alloy coated with electrochemically deposited hydroxyapatite (EDHA), were implanted into canine trabecular bone for 6 h, 7, and 14 days, respectively. Environmental scanning electron microscopy study showed that PSHA coatings had higher bone apposition ratios than those exhibited by bare Ti-6Al-4V and EDHA coatings after 7 days; however, at 14 days after implantation, EDHA and PSHA coatings exhibited similar bone apposition ratios, much higher than that for bare Ti-6Al-4V. The ultrastructure of the bone/implant interface observed by transmission electron microscope showed that the earliest mineralization (6 h-7 days) was in the form of nano-ribbon cluster mineral deposits with a Ca/P atomic ratio lower than that of hydroxyapatite. Later-stage mineralization (7-14 days) resulted in bone-like tissue with the characteristic templating of self-assembled collagen fibrils by HA platelets. Though adhesion of EDHA coatings to Ti-6Al-4V substrate proved problematical and clearly needs to be addressed through appropriate manipulation of electrodepositon parameters, the finely textured microstructure of EDHA coatings appears to provide significant advantage for the integration of mineralized bone tissue into the coatings.

Alloys↗

Bone response adjacent to calcium phosphate electrostatic spray deposition coated implants: an experimental study in goats.

BACKGROUND: A new technique to deposit calcium phosphate (CaP) coatings onto titanium substrates has been developed recently. This electrostatic spray deposition (ESD) technique seems to be very promising. It appears to have clinical advantages such as an inexpensive and simple set-up, high deposition efficiency and the possibility to synthesize layers with a defined surface morphology. OBJECTIVE: The aim of this study was to examine biological properties and osteoconductivity of ESD CaP coatings when inserted into the femoral condyle of a goat. MATERIAL AND METHODS: Twenty-four implants with two gaps, i.e. 1 or 2 mm, were inserted into the femoral condyles of six goats. The implants were coated on one side with either a commercially available plasma-sprayed hydroxyapatite (HAPS) coating or an ESD carbonate apatite (CAESD) coating. The other side of the implant was always left uncoated (Ti). Twelve weeks after implantation the animals were sacrificed and the characteristics of bone ingrowth and bone contact were evaluated. RESULTS: At 3 months, histological and quantitative histomorphometrical measurements demonstrated more bone ingrowth and bone contact for coated sites as compared with uncoated sites. Statistical testing revealed that for both the 1 and 2 mm gaps HAPS (plasma-sprayed hydroxyapatite) as well as CAESD (ESD carbonate apatite) -coated surfaces always had a significantly higher (P<0.05) amount of bone contact than uncoated Ti surfaces. On HAPS surfaces always significantly more bone was present than on CAESD surfaces. Further statistical testing revealed a significant difference in bone ingrowth between the HAPS as well as CAESD and Ti 1+2 mm gap specimens (P<0.05). Further, HAPS 1 mm gaps showed more bone ingrowth than CAESD 1 mm gaps. No significant difference existed between HAPS and CAESD 2 mm gaps. CONCLUSION: On the basis of our observations, we conclude that the used ESD technique is a promising new method to deposit CaP coatings onto titanium substrates. On the other hand, plasma-spray HA-coated implants have a still more favourable effect on the bone response.

Animals↗

Corrosion behavior of a low modulus beta-Ti-45%Nb alloy for use in medical implants.

The corrosion and electrochemical behavior of a low stiffness beta -Ti-45wt.%Nb (Ti45Nb) was studied in solutions that resemble body environment, as compared to Ti6Al4V and Ti-55wt.%Ni (Ti55Ni, Nitinol) alloys currently used in surgical implants. In Ringers' solution, Ti45Nb alloy exhibited an excellent corrosion resistance, comparable to that of Ti6Al4V and much better than that of Nitinol. In acidic environments, beta -Ti45Nb remained passive under conditions where active dissolution was observed for both Ti6Al4V and Nitinol alloys. The results warrant further corrosion and biocompatibility studies of beta -Ti45Nb alloy to establish its suitability as implant material.

Alloys↗

Healing of large (2 mm) gaps around calcium phosphate-coated bone implants: a study in goats with a follow-up of 6 months.

Plasma-sprayed hydroxylapatite (HA) coatings are known for their ability to demonstrate osseointegration with bone. Recently it was found that the amount of bone apposition was strongly reduced 6 weeks after implantation in a goat model if gaps of two millimeters between bone and apatite coating existed. Stability of the apatite coatings examined did not influence the gap-healing ability. This study investigated whether a longer follow-up period of 24 weeks would be sufficient for the restoration of bone apposition on apatite coatings in an identical surgical model with 2 mm gaps, and whether bone apposition on the apatite coatings is influenced by the coating stability. Three coatings were investigated: 25-30% crystalline HA (aHA), 60-63% crystalline HA (cHA), and 85-90% crystalline fluorapatite (FA). Uncoated Ti-6A1-4V implants were used as controls. Implants were inserted in the femoral condyles of both femora of eight goats. Each goat received four implants. Histology revealed that bone formation on each of the apatite coatings remained low and did not increase with an extended follow-up period of 24 weeks. The coatings showed significantly (P < 0.01) more bone contact than the uncoated control implants. The three different coatings did not show significant differences in bone apposition. The aHA coating in most cases had disappeared completely after 24 weeks. Despite the disappearance of the aHA coating, bone contact was seen on the substrate surface without fibrous tissue interposition. The cHA coating showed minor signs of degradation while the FA coatings showed no visible degradation. It is concluded that non-press-fit implantation of apatite-coated implants leads to more bone apposition as compared to uncoated Ti-6A1-4V implants. However, it is suggested by these results that the upper limit of gaps around apatite implants is 2 millimeters in a non-weight-bearing model in goats. Bone apposition will not increase by extending the follow-up period more than six weeks, nor will it be altering the stability of the apatite coatings used.

Animals↗

Differentiation of human bone-derived cells grown on GRGDSP-peptide bound titanium surfaces.

Various surface modifications have been applied to titanium alloy (Ti-6Al-4V) implants, in an attempt to enhance osseointegration; crucial for ideal prosthetic fixation. Despite the numerous studies demonstrating that peptide-modified surfaces influence in vitro cellular behavior, there is relatively little data reporting their effects on bone remodeling. The objective of this article was to examine the effects of chemically modifying Ti-6Al-4V surfaces with a common RGD sequence, a 15-residue peptide containing GRGDSP (glycine-arginine-glycine-aspartate-serine-proline), on the modulation of bone remodeling. The expression of proteins known to be associated with osseous matrix and bone resorption were studied during the growth of human bone-derived cells (HBDC) on these peptide-modified surfaces. HBDC grown for 7 days on RGD surfaces displayed significantly increased levels of osteocalcin, and pro-collagen Ialpha1 mRNAs, compared with the production by HBDC grown on the native Ti-6Al-4V. A pattern that was also reflected at the protein levels for osteocalcin, type I collagen, and bone sialoprotein. Moreover, HBDC grown for 7 and 14 days on RGD-modified Ti-6Al-4V expressed significantly higher level of osteoclast differentiation factors and lower levels of osteoprotegerin and IL-6 proteins compared with other surfaces tested. These results suggest that different chemical treatments of implant material (Ti-6Al-4V) surface result in differential bone responses, not only their ability to form bone but also to stimulate osteoclastic formation.

Amino Acid Sequence↗

Differential healing response of bone adjacent to porous implants coated with hydroxyapatite and 45S5 bioactive glass.

This study tested the hypothesis that the rate and the extent of bone formation adjacent to porous, coated Ti-6Al-4V implants are differentially affected by the type of bioactive ceramic coating. Forty-eight rabbits received cylindrical Ti-6Al-4V intramedullary distal femoral implants bilaterally. Implants for the right limbs were coated with 45S5 Bioglass (45S5). Implants used for the left limbs either were coated with tricalcium phosphate/hydroxyapatite (HA) or were left uncoated as controls (CTL). The 45S5-coated implants histologically and biomechanically were compared to HA-coated and CTL implants at 4, 8, 12, and 16 weeks. After 12 and 16 weeks of healing, more bone and thicker trabeculae were measured histomorphometrically within the implant pores for the 45S5-coated implants compared to the HA-coated and CTL implants (p < 0.05). With time the HA-coated and CTL groups exhibited a significant decline in percent of bone and of trabecular thickness (p < 0.05) while the 45S5-coated implants did not. Biomechanical analyses indicated similar shear strengths for all treatment groups. In summary, 45S5-coated implants exhibited greater bone ingrowth compared to HA-coated and CTL implants, and they maintained their mechanical integrity over time.

Animals↗

New surface modification for Ti-6Al-7Nb alloy: oxygen diffusion hardening (ODH).

PVD-TiN coating and N+ implantation of Ti-6Al-7Nb alloy resulted in surface hardening to a depth of less 3 microns. The new oxygen diffusion hardening (ODH) treatment increased the hardness gradually to 50 microns. PUD-TiN showed an improvement in the tribological properties, while N+ implantation increased the PE wear rate. The wear rate of the ultrahigh-molecular-weight as well as the friction coefficient were reduced to one-half of the values achieved with the combination of CoCrMo-alloy when paired against the ODH-treated surface. In pairing with ZrO2-containing bone cement the ODH-treated surface showed only a minimal reaction.

Corrosion↗

Ectopic bone formation by composites of BMP and metal implants in rats.

Disc-shaped implants of titanium alloy (Ti-6Al-4V) were treated on one side by corundum-blasting (CB) or by coating with hydroxyapatite (HA) or pure titanium (Ti) using plasma spraying. Half of the implants were additionally coated with purified swine BMP-3. The composites and the uncoated controls were implanted into abdominal wall-muscle pouches of rats. 25 days after implantation, ectopic bone formation could be observed macroscopically and histologically in a high frequency in all 3 groups of BMP-coated implants, whereas the controls were constantly inactive. The volumes of induced bone were similar for BMP-3-coated pure Ti and HA implants, while CB implants were significantly less active. Our findings indicate that the bone formation process is influenced by the chemical composition and by the structure of the implant surface.

Alloys↗

The effects of interimplant distances on papilla formation and crestal resorption in implants with a morse cone connection and a platform switch: a histomorphometric study in dogs.

BACKGROUND: Implant esthetics have been the focus of attention for the last few years, and one of the most important points is the effect that interimplant distances can have on papilla formation and bone loss. The aim of this study was to evaluate the effect that distances of 1, 2, and 3 mm between implants after prosthetic restoration will have on crestal bone resorption (from the top of the implant to the bone crest [TI-BC]) and bone resorption (from the top of the implant to the first bone-to-implant contact TI-BIC) in two-stage implants used in a submerged and non-submerged protocol. METHODS: The mandibular bilateral premolars of seven dogs were extracted, and after 12 weeks, each dog received eight implants. The implants were placed so that three interimplant contact points were created, with 1-mm (group 1), 2-mm (group 2), and 3-mm (group 3) distances constructed on each side. The sides and the position of the groups were randomly selected. After 12 weeks, the implants received metallic prostheses with 5 mm between the contact point and the bone crest. After 8 weeks more, the animals were sacrificed. RESULTS: The TI-BC was 0.20 and 0.18 mm for group 1, 0.15 and 0.14 mm for group 2, and 0.15 and 0.15 mm for group 3 for non-submerged and submerged implants, respectively. At the proximal region, the TI-BC was 0.16 mm for non-submerged and 0.16 mm for submerged implants. The TI-BIC was 0.32 and 0.30 mm for group 1, 0.19 and 0.21 mm for group 2, and 0.30 and 0.24 mm for group 3 for non-submerged and submerged implants, respectively. At the proximal region, the TI-BIC was 0.26 mm for non-submerged and 0.25 mm for submerged implants. There was no statistical difference for any of the parameters (analysis of variance [ANOVA]). CONCLUSION: Distances of 1, 2, and 3 mm between implants do not result in statistically significant differences on TI-BC and TI-BIC around submerged or non-submerged implants with a Morse cone connection and a platform switch.

Alveolar Bone Loss↗

Bone ingrowth into weight-bearing porous fiber titanium implants. Mechanical and biochemical correlations.

Bone ingrowth into weight-bearing porous fiber Ti-6Al-4V implants in rat tibias was assessed for the amount, composition, and mineralization rate 3, 12, and 26 weeks after implantation. The data were compared with the ipsi- and contralateral metaphyseal controls and related to the ultimate bending stresses of the distal bone/implant interfaces. From the 3rd to the 12th week there was rapid bone ingrowth and also marked decline in mineralization rate of the ingrowing bone. After 12 weeks the implants were macroscopically pervaded by bone. The ultimate bending stresses increased from the 3rd to the 12th week and reached 45% of that of controls after 26 weeks. There was a linear proportionality between the amount of bone ingrowth and interfacial strength but a curvilinear relationship between bone maturity in terms of calcium/hydroxyproline and calcium/phosphorous ratios and interfacial strength. Stepwise multiple regression analysis showed that the interfacial strength depends on the amount and the maturity of the ingrown bone. Compared with the calcium/hydroxyproline ratio, the calcium/phosphorous ratio was an unreliable predictor of interfacial strength.

Animals↗

Biology of grit-blasted titanium alloy implants.

This study describes the biologic integration of grit-blasted titanium alloy (Ti-6A1-4V) implants that were press fit into the distal femoral canal of young adult rabbits and evaluated by histologic, histomorphometric, and biomechanical methods. Polished and aluminum oxide grit-blasted (4.2 +/- 0.7 microns surface roughness) solid implants were compared with titanium fibermetal implants. Nondecalcified cross sections were studied by histology, histomorphometry, and electron microscopy in the backscatter mode at 3, 6, and 12 weeks after implantation. Pullout strength was measured at 12 weeks. Data were analyzed by analysis of variance and post-hoc Student-Newman-Keuls and Scheffe's tests. The blasted implants had significantly more bone intimately in contact with the implant surface (31%) than the fibermetal (17%), or solid polished implants (15%). By 3 weeks, woven bone had formed directly on the surface of the blasted implants, whereas there was a discrete space between woven bone and the other implants. Active remodeling of bone was shown by fluorochrome uptake at the surface of the blasted implants at 12 weeks after implantation. The strength of fixation of blasted and fiber-metal implants was significantly greater than polished implants at 12 weeks after implantation. Direct attachment of newly formed bone onto the blasted implant surface was confirmed by backscatter electron microscopy. The results of this study indicate that grit-blasted titanium surfaces provide an excellent surface for bone implant integration.

Alloys↗

Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist.

We have investigated the relevance of interleukin-1 receptor type I (IL-1R tI) in the implantation process in vivo in a murine model. Indirect immunofluorescence experiments demonstrate that IL-1R tI is located in mouse endometrial lumenal epithelium with increased intensity in the periimplantation period, whereas IL-1 beta staining is located in the mouse placenta. PMSG/human CG (hCG)-stimulated and mated 12-week-old B6C3F-1 female mice were randomly allocated to three groups: A, control noninjected; B, buffer-injected animals; and C, animals injected ip with 20 micrograms recombinant human IL-1 receptor antagonist (rhIL-1ra) every 12 h beginning on pregnancy day 3. Injections were continued until day 9, and animals were killed 12 h after the last injection. Pregnancy rates in the three groups were: noninjected, 58.8% (10 of 17); buffer-injected, 73.7% (14 of 19); rhIL-1ra-injected, 6.7% (1 of 15), P = 0.0001155, Fisher exact test. To rule out the possibility that pregnancy failure was due to an embryotoxic effect of rhIL-1ra, 2-cell mouse embryos (n = 276) were flushed from the same group of animals used for in vivo experiments and cultured with increasing concentrations of rhIL-1ra: 0 microgram/ml (n = 91), 1 microgram/ml (n = 36), 50 micrograms/ml (n = 36), 100 micrograms/ml (n = 52), and 200 micrograms/ml (n = 61) rhIL-1ra. The percentages of 2-cell mouse embryos reaching the blastocyst stage after 72 h in culture were 85.7%, 91.6%, 94.4%, 96%, and 85.2%, respectively. We further cultured these blastocysts for 5 days on fibronectin-coated plates with or without 200 micrograms/ml rhIL-1ra. In both groups, hatching, attachment to fibronectin, outgrowth, and migration were documented to be similar. Furthermore, our longitudinal morphological study of embryonic implantation in control and rhIL-1ra-injected mice shows that the blockade of IL-1R tI interferes with the attachment of mouse blastocysts to maternal endometrium in vivo. In summary, we demonstrate that blockade of maternal endometrial IL-1R tI with IL-1ra prevents implantation in the mouse by interfering with embryonic attachment, without adverse effects on blastocyst formation, hatching, fibronectin attachment, outgrowth, and migration in vitro.

Animals↗

In vivo effects of RGD-coated titanium implants inserted in two bone-gap models.

RGD (Arg-Gly-Asp) coating has been suggested to enhance implant fixation by facilitating the adhesion of osteogenic cells to implant surfaces. Orthopedic implants are unavoidably surrounded partly by gaps, and these regions represent a challenging environment for osseointegration. We examined the effects of cyclic RGD-coated implants on tissue integration and implant fixation in two cancellous bone-gap models. In canines, we inserted loaded RGD-coated implants with 0.75-mm gap (n = 8) and unloaded RGD-coated implants with 1.5-mm gap (n = 8) into the distal femur and proximal tibia, respectively. Control gap implants without RGD were inserted contralaterally. The titanium alloy (Ti-6Al-4V) implants were plasma sprayed and cylindrical. The observation period was 4 weeks and the fixation was evaluated by push-out test and histomorphometry. Mechanical implant fixation was improved for RGD-coated implants. Unloaded RGD-coated implants showed a significant increase in bone whereas both loaded and unloaded implants showed a significant reduction in fibrous tissue anchorage. The results are encouraging, because RGD had an overall positive effect on the fixation of titanium implants in regions where gaps exist with the surrounding bone. RGD peptide coatings can potentially be used to enhance tissue integration in these challenging environments.

Animals↗

Effect of calcium phosphate surface coating on bone ingrowth onto porous-surfaced titanium alloy implants in rabbit tibiae.

PURPOSE: The purpose of the present study was to determine whether calcium phosphate coating has a significant impact on bone ingrowth into a porous titanium implant. MATERIALS AND METHODS: Porous-surfaced titanium alloy Ti-6Al-4V implants were prepared with or without the addition of a thin surface layer of calcium phosphate applied by sol-gel coating. Implants were placed into the tibiae of 16 rabbits. Implanted sites were allowed to heal for 2 weeks, after which specimens were retrieved for morphometric assessment using backscatter scanning electron microscopy. RESULTS: The data collected show that there is more extensive ingrowth into the porous regions of the calcium phosphate-coated implants than into the control implants. The weighted average ingrowth for the calcium phosphate-coated implants was 2.01, whereas that for the noncoated implants was 1.49; the difference is statistically significant (P <.01). CONCLUSIONS: The addition of a thin layer of calcium phosphate to these implants appears to promote a more extensive implant-to-bone interface by allowing the neck regions to become intimately ingrown with bone even after only 2 weeks of initial healing.

Alloys↗