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Comparison of in vivo dissolution processes in hydroxyapatite and silicon-substituted hydroxyapatite bioceramics.

The incorporation of silicate into hydroxyapatite (HA) has been shown to significantly increase the rate of bone apposition to HA bioceramic implants. However, uncertainty remains about the mechanism by which silicate increases the in vivo bioactivity of HA. In this study, high-resolution transmission electron microscopy was used to observe dissolution from HA, 0.8 wt% Si-HA and 1.5 wt% Si-HA implants after 6 and 12 weeks in vivo. Our observations confirmed that defects, in particular those involving grain boundaries, were the starting point of dissolution in vivo. Dissolution was observed to follow the order 1.5 wt% Si-HA>0.8 wt% Si-HA>pure HA and it was found to be particularly prevalent at grain boundaries and triple-junctions. These observations may help to explain the mechanism by which silicate ions increase the in vivo bioactivity of pure HA, and highlight the enhanced potential of these ceramics for biomedical applications.

Animals↗

Hydroxyapatite coating versus cemented fixation of the tibial component in total knee arthroplasty: prospective randomized comparison of hydroxyapatite-coated and cemented tibial components with 5-year follow-up using radiostereometry.

Fifty-three consecutive patients (57 knees; mean age, 69 years) entered a prospective randomized study to compare the fixation of hydroxyapatite (HA)-coated (29 knees) with cemented (28 knees) tibial components in the Tricon II total knee arthroplasty. The quality of the fixation during 5 years postoperatively was evaluated with radiostereometric analysis (RSA). Three HA-coated implants were revised: 2 owing to infection, and 1 owing to early delamination of the coating and clinical loosening. Eight patients (9 knees) died, 1 patient sustained a stroke, and 1 patient refused investigations after 1 year. In the 40 patients (19 HA-coated, 21 cemented) remaining at 5 years, the magnitude of the micromotion between the HA-coated and cemented groups did not differ. The HA-coated implants displayed most of the migration within the initial 3 months then stabilized, whereas the cemented implants showed an initially lower, but over time continuously increasing migration. Between 1 and 2 years, 4 of 24 HA-coated and 10 of 23 cemented implants migrated >0.2 mm and were categorized unstable, which has been shown to have a prognostic value as regards future aseptic loosening. Progressive radiolucent lines developed in 2 cemented knees, which both were categorized unstable. If HA-coated implants can sustain the forces that threaten the fixation in the early period after implantation, a strong and enduring fixation may be obtained.

Adult↗

Fibroblastic growth and attachment on hydroxyapatite-coated titanium surfaces following the use of various detoxification modalities. Part I: Noncontaminated hydroxyapatite.

Hydroxyapatite-coated titanium alloy test strips were treated with chlorhexidine gluconate, stannous fluoride, citric acid, tetracycline HCl, polymyxin B, hydrogen peroxide, and a plastic Cavitron tip: untreated sterile strips served as controls. The strips were incubated with cultured human gingival and periodontal ligament fibroblasts. Image analysis of three photomicrographs of each test strip (original magnification x350) indicated that the tetracycline HCl treatment resulted in significantly greater cellular surface area coverage compared with the other treatments. Citric acid and the plastic Cavitron tip also stimulated cell attachment, although the results from the Cavitron tip were not significantly different from citric acid or the other treatment groups. The remainder of the modalities and the untreated cellular controls experienced similar cellular coverage.

Cell Adhesion↗

Comparison of the early healing course of porous titanium with hydroxyapatite-coated porous titanium hip implants: clinical considerations for the use of hydroxyapatite coating in total hip replacement.

The role of hydroxyapatite (HA) coating in the fixation of human total joint prostheses remains to be established. Results of animal studies have been favorable, showing very rapid bone formation with a corresponding increase in bone-implant bond strength. In addition, the quantity of bone may be increased. This study compared identical porous titanium primary total hip implants with and without HA in similar patient populations. All of these patients were healthy and reliable, and had optimal bone geometry and bone quality for cementless fixation. The purpose of the study was to contrast the sequence of events, in the first year after surgery, between the two implant groups to identify the contribution of HA to early patient function and early radiographic appearance of the prosthesis. No significant clinical difference could be demonstrated between the two groups at 1 year from surgery. However, the HA group progressed more rapidly when comparing clinical scores at 6 months (P = .0058), and appeared to demonstrate more rapid bone remodeling at 6 months on the femoral side, although this observation did not quite make statistical significance (P = .0618). There was no difference between the acetabular components during the course of this study.

Female↗

Ultrastructural comparison of dissolution and apatite precipitation on hydroxyapatite and silicon-substituted hydroxyapatite in vitro and in vivo.

Recent histological studies have demonstrated that the substitution of silicate ions into hydroxyapatite (HA) significantly increases the rate of bone apposition to HA implants. The enhanced bioactivity of silicon-substituted HA (Si-HA) over pure HA has been attributed to the effect of silicate ions in accelerating dissolution. In the present study, high-resolution transmission electron microscopy (HR-TEM) was employed to compare dissolution of HA and Si-HA in an acellular simulated body fluid (SBF) to dissolution in an in vivo model. HR-TEM observations confirmed a difference in morphology of apatite precipitates in vivo and in SBF: apatite deposits were platelike in vivo and nodular in SBF. Compositional mapping suggested that preferential dissolution of silicon from the implant promotes the nucleation of carbonate apatite around the implant. The in vivo findings illustrated an absence of dissolution at the bone-HA or Si-HA interface, whereas dissolution was extensive from within the implant. The amount of dissolution in acellular SBF was similar to dissolution from within the implant, although the site at which the dissolution nucleates was different: dissolution predominates at the crystallite surfaces in SBF, whereas grain boundary dissolution predominates in vivo. These findings suggest that proteins in the in vivo milieu modify the processes of dissolution from the implant.

Biocompatible Materials↗

Comparison of plasma-sprayed hydroxyapatite coatings and zirconia-reinforced hydroxyapatite composite coatings: in vivo study.

The clinical use of plasma-sprayed hydroxyapatite (HA) coatings on metal implants has been widely adopted because the HA coating can achieve the firmly and directly biological fixation with the surrounding bone tissue. However, the long-term mechanical properties of HA coatings has been concern for the long-term clinical application. Previous research showed that the concept of adding ZrO2 as second phase to HA significantly increased the bonding strength of plasma-sprayed composite material. The present work aimed to explore the biological properties, including the histological responses and shear strength, between the plasma-sprayed HA and HA/ZrO2 coating, using the transcortical implant model in the femora of canines. After 6 and 12 weeks of implantation, the HA coating revealed the direct bone-to-coating contact by the backscattered electron images (BEIs) of scanning electron microscope (SEM), but the osseointegration was not observed at the surface of HA/ZrO2 coating. For new bone healing index (NBHI) and apposition index (AI), the values for HA implants were significantly higher than that for HA/ZrO2 coatings throughout all implant periods. After push-out test, the shear strength of HA-coated implants were statistically higher than HA/ZrO2 coated implants at 6- and 12-week implantation, and the failure mode of HA/ZrO2 coating was observed at the coating-bone interface by SEM. The results indicate that the firm fixation between bone and HA/ZrO2 has not been achieved even after 12-week implantation. Consequently, the addition of ZrO2 could improve the mechanical properties of coatings, while the biocompatibility was influenced by the different material characteristics of HA/ZrO2 coating compared to HA coatings.

Animals↗

Development of hydroxyapatite bone scaffold for controlled drug release via poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings.

A scaffold-coating design, the hydroxyapatite (HA) porous bone scaffold coated with poly(epsilon-)caprolactone (PCL) and HA powder hybrids, was developed for use as tissue-regeneration and controlled-release system. An antibiotic drug, tetracycline hydrochloride (TCH), was encapsulated within the hybrid coating layer through a dip-coating and solvent-casting method. Coating cycle and drug loading amount differed to control the level of drug-release rate. The HA scaffold framework, obtained by a polymeric foam reticulate method, exhibited a highly porous structure, with porosity and pore size of approximately 87% and 180 microm, respectively. The hybrid layer, consisting of PCL sheet and HA fine powders, was uniformly coated on the scaffold surface. The coating layer exhibited only PCL and HA phases and structures, revealing no chemical interaction among the coating components, as observed by X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) analyses. The coated-HA scaffolds showed an effective stress distribution behavior in response to an applied load, as confirmed by the compressive stress-strain curve. The mechanical properties of the coated scaffolds were improved highly with coatings; the compressive strength and elastic modulus of the cyclic coated scaffolds were approximately 3-4 times, and the energy absorption were approximately 8 times, higher than those without coating. These improvements were attributed mainly to the shielding of framework flaws by a flexible coating layer and partially to the thicker stems (porosity reduction). The dissolution of the coated scaffolds in a phosphate-buffered saline (PBS) solution increased with incubation time. The drug was released sharply within the initial several hours ( approximately 2 h), but the rate decreased further, showing a sustained release. The release amount was well controlled via coating-cycle and initial drug loading amount, suggesting the effectiveness of the coating-scaffold design as a drug-delivery system.

Bone and Bones↗

Comparison of the early production of extracellular matrix on dense hydroxyapatite and hydroxyapatite-coated titanium in cell and organ culture.

In order to investigate the earliest changes at the bone-hydroxyapatite (HA) interface, two materials, dense HA and HA-coated titanium alloy, were investigated for their ability to stimulate production of extracellular matrix both in cell and organ culture. Osteoblast-like cells were obtained from rabbit calvariae after preliminary culture for 3 d and seeded out onto the materials. When these cells were grown in culture on the dense HA no matrix production was seen with the scanning electron microscope after 4 d, but there did appear to be matrix produced on the rougher surface of the HA coating. In contrast, extracellular matrix production was greatly increased in organ culture where the material was placed on a section of bone, particularly on the HA coating, where it formed an organized layer of collagen within 4 d. These results showed that extracellular matrix production by both osteoblastic cells and in calvarial culture was greater on the HA coatings than dense HA. In addition, organ culture allows the investigation of the earliest changes in the bone-HA interface without having to undertake in vivo implantation studies of such short duration.

Alloys↗

Comparison of two hydroxyapatite-coated femoral stems: clinical, functional, and bone densitometry evaluation of patients randomized to a regular or modified hydroxyapatite-coated stem aimed at proximal fixation.

Clinical function, bone mineral density (BMD), and radiographs of 80 randomly allocated, hydroxyapatite-coated femoral stems of two differing lengths were studied for 2 years. The short stem was optimized for proximal fixation. The predictive value of bone densitometry was also studied. After 2 years, significantly more bone apposition and a higher BMD percentage were observed in Gruen zone 7 of the short stem. We conclude that stem design can be enhanced to achieve more proximal fixation. However, we found a higher incidence of pain with the short stem, indicating a trade-off between increased proximal fixation and diminished overall mechanical stability. No strong correlations between clinical function and radiographic evaluation of remodeling were found with BMD, suggesting that dual-energy x-ray absorptiometry has no predictive value for short-term clinical outcome.

Absorptiometry, Photon↗

Plasma-sprayed hydroxyapatite+titania composite bond coat for hydroxyapatite coating on titanium substrate.

A two-layer hydroxyapatite (HA)/HA+TiO(2) bond coat composite coating (HTH coating) on titanium was fabricated by plasma spraying. The HA+TiO(2) bond coat (HTBC) consists of 50 vol% HA and 50 vol% TiO(2) (HT). The microstructural characterization of the HTH coatings before and after heat treatment was conducted by using scanning electron microscopy (SEM), electron probe microanalyser (EPMA), X-ray diffractometer (XRD) and transmission electron microscopy (TEM), in comparison with that of HT coating and pure HA coating. The results revealed that HA and TiO(2) phases layered in an alternating pattern within the HTBC, and the HTBC bonded well to HA top coating (HAT coating) and Ti substrate. The as-sprayed HT coating consists mainly of crystalline HA, rutile TiO(2) and amorphous Ca-P phase. The post-spray heat treatment at 650 degrees C for 120 min effectively restores the structural integrity of HA by transforming non-HA phases into HA. It was found that there exists interdiffusion of the elements within the HTBC, but no chemical product between HA and TiO(2), such as CaTiO(3) was formed. The cross-sectional morphologies confirmed that there is a shift towards a relatively tighter bonding from the HAT coating/HTBC interface in the as-sprayed HTH coating to the HTBC/Ti substrate interface in the heat-treated HTH coating. On quenching the coatings into water, the surface cracking indicates more apparently the positive effect of the HTBC on the decrease of residual stress in HAT coating. The in situ surface cracking also suggests that the stress on the surface of the HTH coating is stable under subjection to a repetitious heat treatment. The toughening and strengthening of HTBC is thought to be mainly due to TiO(2) as obstacles embarrassing cracking, the reduction of the near-tip stresses resulting from stress-induced microcracking and the decrease of CTE mismatch. In the HTH composite coating, the HAT coating is toughened by the decreased CTE mismatch with Ti through the addition of HTBC, which bonds well to the Ti substrate via its TiO(2) hobnobbing with the Ti oxides formed on Ti substrate.

Coated Materials, Biocompatible↗

Adsorption and release studies of sodium ampicillin from hydroxyapatite and glass-reinforced hydroxyapatite composites.

As a potential therapy for periodontitis, sodium ampicillin, a broad spectrum antibiotic, was adsorbed onto hydroxyapatite (HA) and glass-reinforced hydroxyaptite (GR-HA) composites, and was subsequently released in vitro. The sodium ampicillin, was adsorbed more on HA compared to the GR-HA composites. X-ray diffraction (XRD) and Rietveld analysis were used to identify and quantify the levels of HA and beta-tricalcium phosphate (beta-TCP) in the microstructure of the GR-HA composites. Lattice parameters changes were observed for the beta-TCP phase dependant on the amount of glass added. The release kinetics were shown to be divided into three stages, the first of which where a large amount of sodium ampicillin is released, followed by a slower release rate and then a final stage where the release amount approaches zero, until no more sodium ampicillin was present. X-ray photoeletron spectroscopy (XPS) studies were carried out in order to ensure that the entire antibiotic adsorbed onto the materials had been released. These kinetics studies have indicated the possibility of using these materials as possible carriers for drug delivery.

Adsorption↗

Effect of hydroxyapatite morphology/surface area on the rheology and processability of hydroxyapatite filled polyethylene composites.

The commercial success of hydroxyapatite (HA) filled polyethylene composite has generated growing interest in improving the processability of the composite. A number of synthetic procedures and post synthesis heat treatment of HA has lead to the availability of powders with widely varying morphological features. This paper addresses the effect of morphological features of HA on the rheology and processability of an injection-moulding grade HA-HDPE composite. The results showed that low surface area HA filled composite exhibited better injection processing characteristics through improved rheological responses. The effect of reducing the surface area of the filler is to require less polyethylene to wet the filler and allows more polyethylene to be involved in the flow processes. These changes reduced the temperatures and pressures required for successful processing.

Biocompatible Materials↗

Effect of morphological features and surface area of hydroxyapatite on the fatigue behavior of hydroxyapatite-polyethylene composites.

The effect of surface area and morphological features of filler particles on the fatigue behavior of hydroxyapatite-filled high-density polyethylene composites was studied. Composites containing 40 vol % filler were injection-molded into tensile bars, gamma-irradiated, and subjected to sinusoidal tensile fatigue at a frequency of 2 Hz. To simulate the physiological environment, the tests were conducted at 37 degrees C in saline. Results showed that properties such as secant modulus, cyclic energy dissipation, dynamic creep strain, hysteresis loops, and even fracture surfaces differ depending on the morphology and surface area of the fillers used.

Composite Resins↗

Comparison of hydroxyapatite and hydroxyapatite tricalcium-phosphate coatings.

This study compared the effects of hydroxyapatite (HA) coating and biphasic HA/tricalcium-phosphate (HA/TCP) coating on the osseointegration of grit-blasted titanium-alloy implants. Each coated implant was compared with uncoated grit-blasted implants as well. The implants were press-fit into the medullary canal of rabbit femora, and their osseointegration was evaluated 3 to 24 weeks after surgery. The coated implants had significantly (P<.05) greater new bone ongrowth than the uncoated implants (HA, 56.1 +/- 3.1%; HA/TCP, 53.8 +/- 2.6%; uncoated, 32.2 +/- 1.4% of the implant perimeter, 12 weeks). Unmineralized tissue (cartilage and osteoid) was seen on the uncoated implants but never on the coated implants. The coated implants had significantly (P<.05) greater interfacial shear strength than the uncoated implants (HA, 4.1 +/- 0.4 MPa; HA/TCP, 4.8 +/- 0.5 MPa; uncoated, 2.6 +/- 0.2 MPa, 12 weeks). There was no difference between HA and HA/TCP coating in regard to new bone growth or interfacial shear strength. These data show a comparable enhancement effect of HA and HA/TCP coatings on the osseointegration of titanium-alloy implants.

Animals↗

Successful transpedicular lumbar interbody fusion by means of a composite of osteogenic protein-1 (rhBMP-7) and hydroxyapatite carrier: a comparison with autograft and hydroxyapatite in the sheep spine.

STUDY DESIGN: Transpedicular lumbar interbody fusion (TLIF) was performed in a sheep model comparing three treatment groups: a composite of osteogenic protein (OP)-1 and hydroxyapatite carrier (HA), HA without OP-1, and autograft. OBJECTIVE: To evaluate the efficacy of the composite of OP-1 and HA (HA-OP-1) in achieving reliable TLIF. SUMMARY OF BACKGROUND DATA: Anterior fusion techniques directly address disc-related problems and achieve primary axial stability. However, they are characterized by high morbidity. Alternatively, the theoretically advantageous posterior TLIF technique using autograft fails clinically because it lacks compressive stability. METHODS: In 36 sheep, lumbar vertebrae L4 to L6 were instrumented posteriorly. Endoscopically assisted TLIF of L4 to L5 was performed. In 12 sheep, the defect was filled with injectable HA-OP-1. Another 12 sheep were treated with HA and another 12 with autograft. Animals were killed at 8 weeks and evaluated by radiologic, histologic, and histomorphometric analysis and by fluorochrome labeling. RESULTS: Only 10 autograft sheep were available for evaluation. Radiologically and histologically, TLIF with HA-OP-1 led to a fusion rate of 10 in 12 compared with autograft (one in 10 fused) and HA (two in 12 fused) ( = 0.0016). Semiquantitative radiologic and histologic scoring also revealed significant differences with superiority of HA-OP-1 ( = 0.0011). Compared with HA, HA-OP-1 presented significantly more ossification at the bone-cement interface ( = 0.0003) and less cement resorption ( = 0.0209). In four of 12 HA sheep, excessive resorption was responsible for local aseptic inflammation. CONCLUSIONS: Biointegration of the osteoconductive HA does not occur, because shear forces cause early HA fracture, subsequent fragmentation, and gross resorption (initiating severe inflammation in four of 12 sheep). In contrast, osteoinductive effects of HA-OP-1 enable bio-integration, resulting in full osseous composite sheathing and solid fusion. By use of this composite, TLIF is successfully applied in sheep. Harvesting autograft and the anterior approach are avoided.

Animals↗

A 6-year unloaded hydroxyapatite-coated dental implant placed into an extraction socket in conjunction with nonresorbable hydroxyapatite grafting material: histologic evaluation.

A submerged hydroxyapatite (HA)-coated implant placed into a fresh extraction socket in conjunction with a nonresorbable HA graft was harvested after 6 years of unloaded healing. The implant and surrounding bone were processed for histologic analysis. The HA coating appeared to be stable and homogenous. An excellent bone-to-implant contact could be found along the entire implant length. No signs of HA resorption or detachment were found. The HA graft was still recognizable histologically around the apical third of the implant. Light microscopy revealed a good osteoconductive ability of the HA particles, which did not show any signs of remodeling or resorption. These findings suggest that HA-coated implants may be able to maintain optimal osseointegration over time, even in the absence of loading.

Adult↗

Fibronectin preadsorbed on hydroxyapatite together with rough surface structure increases osteoblasts' adhesion "in vitro": the theoretical usefulness of fibronectin preadsorption on hydroxyapatite to increase permanent stability and longevity in spine implants.

OBJECTIVE: The aim of this study was to investigate the contribution of fibronectin (FN) preadsorption to enhance osteoblast adhesion and strength on hydroxyapatite (HA) used either as osteoconductive bone substitute or precoating of pedicle screws and cages in spine surgery. METHODS: HA substrata with two different surface roughness values (rough HA180 and smooth HA1200) were produced, and human osteoblasts were seeded after culturing on them. Prior to osteoblast seeding, the HA substrata were immersed in FN solution. Osteoblast attachment on each of the two HA substrata was evaluated by recording the number of cells, whereas osteoblast adhesion strength was determined by measuring the shear stress required to detach the cells from the HA substrates. RESULTS: FN preadsorption increased the number of attached osteoblasts on smooth and rough HA substratum at 40% and 62%, respectively, whereas it increased osteoblast attachment strength on the smooth and rough substratum at 165% and 73%, respectively. CONCLUSIONS: This study showed that FN preadsorption and rough HA surface texture synergistically increased "in vitro" both the number and the adhesion strength of human osteoblasts. Further studies in primates and humans should be carried out to disclose the clinical relevance (increase implant's stability and longevity) of the above-mentioned observations.

Adsorption↗