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Hydroxyapatite induces autolytic degradation and inactivation of matrix metalloproteinase-1 and -3.

In the course of studies to identify a protease capable of producing a long-lived 50 kDa fragment of bone acidic glycoprotein-75 (BAG-75), it was observed that incubation of matrix metalloproteinase (MMP)-3 (stromelysin 1) with preparations of BAG-75 led to inactivation of proteolytic function, e.g., an inability to fragment 125I-labeled BAG-75 added subsequently. MMP-1 (interstitial collagenase) was also inactivated by exposure to BAG-75 preparations. Investigation of the mechanism revealed that BAG-75 preparations contained millimolar levels of inorganic phosphate which formed hydroxyapatite crystals under digestion conditions. Hydroxyapatite crystals alone and in BAG-75-hydroxyapatite complexes induced the autolytic degradation of both active and precursor forms of MMP-1 and MMP-3. Autolytic degradation in the presence of hydroxyapatite was demonstrated by a loss in catalytic function assayed with peptide and/or protein substrates, and, by fragmentation into polypeptides of <10 kDa. The fate of MMP-3 incubated with hydroxyapatite depends upon the time of incubation, the free calcium concentration, and the concentration of crystals. Specifically, hydroxyapatite-induced autolysis requires a near physiological free calcium concentration of 0.5-1.0 mM. Autolysis was maximal in the presence of 150 microg/ml hydroxyapatite where MMP-3 was only partially bound to crystals. However, autolysis also occurred at higher crystal concentrations where all input MMP-3 was bound (>1000 microg/ml), suggesting that autolysis may be mediated by bound enzyme. The effect of hydroxyapatite appears to be specific for MMP-1 and MMP-3 since the catalytic activity of chymotrypsin, trypsin, papain, and thermolysin remained unchanged after exposure to hydroxyapatite. These results document for the first time a novel catalytic role for hydroxyapatite crystals in vitro and provide an initial biochemical characterization of the intermolecular, autolytic, calcium ion-dependent, matrix metalloproteinase-specific degradative mechanism.

Animals↗

The influence of a hydroxyapatite and tricalcium-phosphate coating on bone growth into titanium fiber-metal implants.

A study was done in rabbits to determine the effect of a hydroxyapatite and tricalcium-phosphate coating on bone growth into titanium fiber-metal implants. Titanium fiber rods with a solid titanium core were implanted bilaterally into the distal aspect of the femora of fifty-five New Zealand White rabbits. One rod was uncoated and the other rod was surface-coated with hydroxyapatite and tricalcium phosphate by the plasma-spray technique. Thirty-five rabbits were labeled sequentially with fluorochromes; killed at one, two, three, four, six, twelve, or twenty-four weeks after the operation; and studied histologically and histomorphometrically. The implants in the remaining twenty rabbits were subjected to pull-out testing to determine the shear strength at the implant-bone interface at three, six, twelve, and twenty-four weeks after the operation. Histomorphometry revealed significant effects of the hydroxyapatite and tricalcium-phosphate coating. When whole-group means (which included all time-points) were compared, it was found that 44 per cent of the perimeter of the hydroxyapatite and tricalcium-phosphate-coated implants was covered with bone compared with 12 per cent of the perimeter of the uncoated implants. The percentage of the internal surface of the implant that was covered with bone was also significantly higher in the hydroxyapatite and tricalcium-phosphate-coated implants: 27 per cent of the internal surface of the coated implants was covered compared with 8 per cent in the uncoated implants. The amount of bone in the pores of the implants was also higher in the hydroxyapatite and tricalcium-phosphate-coated implants: 12 per cent of the available pore space in the hydroxyapatite and tricalcium-phosphate-coated implants was filled with bone compared with 4 per cent in the uncoated implants. Scanning electron microscopy of the implants, done in backscatter mode, demonstrated apposition of new bone directly on the hydroxyapatite and tricalcium-phosphate coating, with variable degrees (amounts) of hydroxyapatite and tricalcium-phosphate resorption and new-bone replacement over time. Bone was never directly apposed to uncoated titanium fiber-metal. The pull-out strength of the hydroxyapatite and tricalcium-phosphate-coated implants was consistently greater than that of the uncoated implants, at all time-periods.

Animals↗

[Sorption kinetics of fluoride by artificial and natural hydroxyapatite].

The nature and kinetics of fluoride uptake by hydroxyapatite under various conditions remain the object of interest. This problem was now investigated with an experimental model reproducing as closely as possible the conditions in vivo. The aim of this work was: (1) to study the kinetics of fluoride uptake by natural and artificial hydroxyapatite depending on experimental conditions and to determine the reaction rate constants; (2) to describe the equilibrium of fluoride uptake with adsorption isotherms and develop a best fit mathematical model for the process taking place under various experimental conditions; (3) to determine and compare the capacity for fluoride uptake by natural and artificial hydroxyapatite depending on experimental conditions. Attention has focused on the equilibrium and kinetics of the process of fluoride uptake under conditions as similar to those in a living organism as it is possible to reproduce in vitro. Those conditions represented just one of sixteen various experimental setups differing as to process parameters of the experimental system. The equilibria and kinetics of the experimental system were determined basing on measurements of selected parameters. Adsorption isotherms were obtained experimentally and a best fit mathematical model was developed to describe the process. Additionally, maximal capacity for fluoride uptake was calculated, as well as equilibrium constants, adsorption and desorption rate constants for both hydroxyapatite types. The following conclusions were drawn: 1. Fluoride uptake by artificial and natural hydroxyapatite is a biphasic process essentially independent of conditions in the reaction environment adopted in the present work. The first phase is rapid and does not exceed some 15 minutes. The second phase is much slower and takes place over a period of several dozen hours. 2. Fluoride sorption by both hydroxyapatites is essentially a physico-chemical process which can mathematically be best described with Langmuir and Langmuir-Freundlich adsorption isotherms. Under conditions of equilibrium, the adsorbed substance forms a monolayer on the surface of the sorbent. 3. The binding of fluoride by natural hydroxyapatite is stronger than by its artificial counterpart. 4. The stability of fluoroapatite formed during fluoride uptake by natural hydroxyapatite is greater than that of its artificial counterpart. 5. Natural hydroxyapatite has a relatively large capacity for fluoride ions under experimental conditions adopted in the present work. This capacity exceeds that of artificial hydroxyapatite in spite of smaller specific surface of the natural substance.

Adsorption↗

Experimental usage of hydroxyapatite preadsorption with fibronectin to increase permanent stability and longevity of spinal implants.

UNLABELLED: Hydroxyapatite has been used in orthopaedic and particularly in spinal surgery by precoating implants to indirectly increase osteoblasts' adhesion and subsequently their stability and longevity. Fibronectin preadsorption synergistically with appropriately constructed hydroxyapatite's surface texture to enhance osteoblasts' adhesion has not been, to the authors' knowledge, previously investigated. In osteoporotic spines, methods to increase implant stability (pedicle screws and cages) are of major value. OBJECTIVE: This experimental study investigated the contribution of fibronectin preadsorption to enhance osteoblasts' adhesion and strength on hydroxyapatite. METHODS: Hydroxyapatite substrata with two different surface roughnesses (rough HA180 and the smooth HA1200) were produced and human osteoblasts were seeded on them after culture. Prior to osteoblasts seeding, the hydroxyapatite substrata were immersed in fibronectin solution. Osteoblast attachment on each of the two hydroxyapatite substrata was evaluated by recording the number of cells, while the osteoblast's adhesion strength was determined by measuring the shear stress required to detach the cells from the hydroxyapatite substrates. RESULTS: Fibronectin preadsorption increased the number of attached osteoblasts on smooth and rough hydroxyapatite substratum at 40% and 62% respectively, while it increased osteoblast attachment strength on the smooth and rough substratum at 165% and 73% respectively. CONCLUSIONS: Fibronectin preadsorption and smooth hydroxyapatite surface texture synergistically increased the adhesion's strength of human osteoblasts "in vitro", while preadsorption and rough hydroxyapatite surface increased the number of attached osteoblasts. Further studies in primates and human beings should be carried out to disclose the clinical relevance of the above mentioned observations in spine surgery.

Coated Materials, Biocompatible↗

Hydroxyapatite accelerates differentiation and suppresses growth of MC3T3-E1 osteoblasts.

Hydroxyapatite describes both the natural mineral phase of bone as well as the widely used calcium-phosphate implant substitute. Given that hydroxyapatite is a major component of the in vivo surface with which osteoblasts interact, it is surprising that most studies examining the regulation of osteoblast growth and differentiation utilize plastic surfaces. Here we demonstrate that the phenotype of mouse MC3T3-E1 osteoblasts is significantly altered on hydroxyapatite compared with plastic surfaces. Specifically, alkaline phosphatase activity and messenger RNA levels, markers of early stages of osteoblast differentiation, are increased in osteoblasts cultured on hydroxyapatite. The precocious appearance of alkaline phosphatase activity on the hydroxyapatite surface suggests that osteoblast differentiation is activated earlier compared with plastic surfaces. Osteocalcin expression, a marker of late-stage differentiation, is also increased on hydroxyapatite and further demonstrates enhanced differentiation. Cell counts indicate that fewer osteoblasts are present on hydroxyapatite versus plastic surfaces 24 h after plating. Measurement of osteoblast attachment, apoptosis, and necrosis indicated no differences between surfaces. In contrast, the number of bromodeoxyuridine-incorporating cells was significantly decreased on hydroxyapatite compared with plastic surfaces. Taken together, our findings indicate that hydroxyapatite enhances osteoblast differentiation while also suppressing growth.

Alkaline Phosphatase↗

The effect of phosphatidylserine on in vitro hydroxyapatite growth and proliferation.

The acidic phospholipid phosphatidylserine (PS) has been reported to have variable effects on in vitro hydroxyapatite proliferation. PS promotes in vitro mineralization in systems in which calcium-PS-phosphate complexes are allowed to form, and inhibits in vitro mineralization when incorporated into liposomes. To investigate these diverse effects, a Langmuir adsorption isotherm was used to determine the affinity of PS for hydroxyapatite crystals, based on binding of 14C-PS to synthetic hydroxyapatite crystals of specific surface 54 m2/g. Using this model, PS was found to bind to hydroxyapatite crystals with an affinity comparable to that of the amino acid phosphoserine (K = 3.33 ml/mumol). Coating the surface of hydroxyapatite seed crystals with PS reduced their rate of proliferation in a metastable calcium phosphate solution in which calcium-PS-phosphate complexes were previously shown to promote hydroxyapatite formation. The extent of inhibition of hydroxyapatite seeded growth was directly related to the proportion of the hydroxyapatite surface covered with PS. These data suggest that PS may have multiple effects on hydroxyapatite formation in situ, and that mineral-PS interactions can retard crystal proliferation.

Calcium Phosphates↗

Correlative radiological, self-assessment and clinical analysis of evolution in instrumented dorsal and lateral fusion for degenerative lumbar spine disease. Autograft versus coralline hydroxyapatite.

This prospective longitudinal randomized clinical and radiological study compared the evolution of instrumented posterolateral lumbar and lumbosacral fusion using either coralline hydroxyapatite (CH), or iliac bone graft (IBG) or both in three comparable groups, A, B and C, which included 19, 18 and 20 patients, respectively, who suffered from symptomatic degenerative lumbar spinal stenosis and underwent decompression and fusion. The patients were divided randomly according to the graft used and the side that it was applied. The spines of group A received autologous IBG bilaterally; group B, IBG on the left side and hydroxyapatite mixed with local bone and bone marrow on the right side; group C, hydroxyapatite mixed with local bone and bone marrow bilaterally. The age of the patients in the groups A, B and C was 61+/-11 years, 64+/-8 years and 58+/-8 years, respectively. The SF-36, Oswestry Disability Index (ODI), and Roland-Morris (R-M) surveys were used for subjective evaluation of the result of the surgery and the Visual Analogue Scale (VAS) for pain severity. Plain roentgenograms including anteroposterior, lateral and oblique views, and lateral plus frontal bending views of the instrumented spine and CT scan were used to evaluate the evolution of the posterolateral fusion in all groups and sides. Two independent senior orthopaedic radiologists were asked to evaluate first the evolution of the dorsolateral bony fusion 3-48 months postoperatively with the Christiansen's radiologic method, and secondly the hydroxyapatite resorption course in the spines of groups B and C. The diagnosis of solid spinal fusion was definitively confirmed with the addition of the bending views, CT scans and self-assessment scores. The intraobserver and interobserver agreement (r) for radiological fusion was 0.71 and 0.69, respectively, and 0.83 and 0.76 for evaluation of CH resorption. T(12)-S(1) lordosis and segmental angulation did not change postoperatively. There was no radiological evidence for non-union on the plain roentgenograms and CT scans. Radiological fusion was achieved 1 year postoperatively and was observed in all groups and vertebral segments. Six months postoperatively there was an obvious resorption of hydroxyapatite granules at the intertransverse intersegmental spaces in the right side of the spines of group B and both sides of group C. The resorption of hydroxyapatite was completed 1 year postoperatively. Bone bridging started in the third month postoperatively in all instrumented spines and all levels posteriorly as well as between the transverse processes in the spines of the group A and on the left side of the spines of group B where IBG was applied. SF-36, ODI, and R-M score improved postoperatively in a similar way in all groups. There was one pedicle screw breakage at the lowermost instrumented level in group A and two in group C without radiologically visible pseudarthrosis, which were considered as having non-union. Operative time and blood loss were less in the patients of group C, while donor site complaints were observed in the patients of the groups A and B only. This study showed that autologous IBG remains the "gold standard" for achieving solid posterior instrumented lumbar fusion, to which each new graft should be compared. The incorporation of coralline hydroxyapatite mixed with local bone and bone marrow needs adequate bleeding bone surface. Subsequently, hydroxyapatite was proven in this series to not be appropriate for intertransverse posterolateral fusion, because the host bone in this area is little. However, the use of hydroxyapatite over the decorticated laminae that represents a wide host area was followed by solid dorsal fusion within the expected time.

Aged↗

Hydroxyapatite - a reagent for the separation of free and antibody-bound steroid during the radioimmunoassay.

The use of hydroxyapatite to absorb antibody-bound steroid and thus separate free and antibody-bound steroid during radioimmunoassay has been examined using three steroid antisera (to testosterone, to 17-hydroxyprogesterone and to estradiol-17beta). For all three antisera studied the separation was shown to be independent of length of time in contact with hydroxyapatite (up to 1h); temperature variations from 4 degrees -37 degrees and pH over the range 4.9-8.0. The presence of protein affected the absorption of antibody-bound steroid but this effect could be overcome by the addition of increasing amounts of hydroxyapatite. Further increase in the amount of hydroxyapatite added had no effect on the separation of free and bound steroid. Sodium phosphate buffers of molarity greater than 0.01M eluted antibody-bount steroid from hydroxyapatite, but Tris-HC1 buffers up to molarities of 0.1 M had no effect. Hydroxyapatite when used as a dry powder had the same effects as suspensions. No effect on the cross-reactivities of the antisera used could be demonstrated when hydroxyapatite was used and plasma testosterone assays on 22 plasma samples using hydroxyapatite gave essentially the same results as assays on the plasma using a coated-tube assay. Hydroxyapatite can also be successfully pumped along small bore plastic tubing without settling and can thus be used in automated immunoassay systems.

Estradiol↗

Hydroxyapatite paste (BoneSource) used as an onlay implant for supraorbital and malar augmentation.

This study was designed to evaluate hydroxyapatite paste (BoneSource; Leibinger Corp., Dallas, TX) as an alloplastic implant for supraorbital and malar augmentation. Ten male Sprague-Dawley rats had cylindrical onlay implants made of the hydroxyapatite cement placed above their left orbits on the supraorbital rim. Size-matched Medpor implants were placed similarly on the right side. To test the utility of this new material in the midface, hydroxyapatite paste and Medpor implants were also placed in the right malar regions of a different set of rats. The implants were left in situ for 6 months and examined for evidence of bone ingrowth, infection, migration, resorption, and detrimental effects on the surrounding tissue. All hydroxyapatite cement implants provided excellent soft tissue projection and demonstrated steadfast adherence to the adjacent bone. The surface of the hydroxyapatite implant in contact with the native bone demonstrated evidence of native bony ingrowth into approximately 12% of the implant. There was no evidence of implant migration or gross infection. There was no bony resorption below the hydroxyapatite paste, but four of the Medpor implants showed evidence of this in the underlying bone. Only one negative aspect to the use of hydroxyapatite cement paste as an onlay implant was identified. Two of the supraorbital and one of the malar hydroxyapatite implants had approximately 20 to 25% volume loss during the experimental period (P = 0.05). Overall, the vast majority of the implants retained their original form. We concluded that hydroxyapatite paste may possibly be used to effectively augment bone in the supraorbital and malar regions. Its biocompatibility, excellent bony adherence, and tendency to be replaced by natural bone may make it suitable for the aesthetic patient. The possible resorptive aspects of the material need to be evaluated further.

Animals↗

Revision of failed pedicle screws using hydroxyapatite cement. A biomechanical analysis.

STUDY DESIGN: The biomechanical influence of in situ setting hydroxyapatite cement was examined for use in pedicle screw revision surgery. Pull-out testing of control and pedicle screws augmented with hydroxyapatite cement was performed in human cadaver vertebrae. OBJECTIVES: To determine the immediate effect of using hydroxyapatite cement to augment revision pedicle screws after failure of the primary pedicle screw fixation. SUMMARY OF BACKGROUND DATA: The potential problems associated with using polymethylmethacrylate to augment revision pedicular instrumentation have prompted the search for other solutions. The introduction of resorbable hydroxyapatite pastes may have provided new biocompatible solutions for pedicle screw revision. METHODS: Ten human cadaver vertebrae were instrumented with 6.0-mm pedicle screws in each pedicle. The screws were loaded to failure in axial tension (pull-out). The failed pedicles then were instrumented with 7.0-mm pedicle screws, either augmented with hydroxyapatite cement or nonaugmented, which also were loaded to failure. Finally, the nonaugmented 7.0-mm screw hole was reinstrumented with a hydroxyapatite cement-augmented, 7.0-mm pedicle screw and loaded to failure. RESULTS: The pull-out strength of the 7.0-mm, hydroxyapatite cement-augmented screws was 325% (P = 2.9 x 10(-5)) of that of the 6.0-mm control screws, whereas the strength of the 7.0-mm nonaugmented screws was only 73% (P = 2.0 x 10(-2)) of that of the 6.0-mm control screws. The 7.0-mm screws augmented with hydroxyapatite cement also were able to salvage 7.0-mm pull-out sites to 384% (P = 6.9E-5) of the pull-out strength of the 7.0-mm nonaugmented screws. CONCLUSIONS: Hydroxyapatite cement may be a mechanically viable alternative to polymethyl methacrylate for augmenting revision pedicular instrumentation and should be considered for future experimental, animal, and clinical testing.

Biomechanical Phenomena↗

[Pull-out strength and bone tissue reaction of plasma-sprayed hydroxyapatite coatings with different thicknesses or substrates].

Synthetic hydroxyapatite has been reported to have good histocompatibility, while metal to have good mechanical properties in vivo. This author coated hydroxyapatite on SUS316L stainless steel and titanium rods, using plasma-spraying techniques. Then they were implanted into tubular bones of five dogs. The pull-out strength of hydroxyapatite-coated metals was found to be stronger than that of non-coated metals and increased with passage of the time. After four weeks postoperatively, the coating layer fractured between hydroxyapatite and the metal by the pull-out test. A numerous new bone in contact with hydroxyapatite was observed. Fifty microns is found to be an ideal thickness of the coating layer. The pull-out strength of hydroxyapatite-coated titanium was higher, comparing to that of hydroxyapatite-coated SUS316L stainless steel. These results suggested that perovskite and rutile existed at the interface between hydroxyapatite and titanium after plasma-spraying and made hydroxyapatite to bond tightly to the titanium. Synthetic perovskite showed no pathological reactions to canine bone tissue.

Animals↗

Does coralline hydroxyapatite conduct fusion in instrumented posterior spine fusion?

OBJECTIVES: This study was conducted to investigate the course of incorporation of coralline hydroxyapatite in human spine. SUMMARY OF BACKGROUND DATA: Conventional techniques for surgical treatment of spine have a substantial failure rate and associated morbidity. Bone graft substitutes are an alternative technique to enhance fusion rates and limit the morbidity associated with spine fusion using autologous iliac crest bone graft. There are some experimental studies supporting the use of hydroxyapatite in spine surgery. MATERIAL & METHODS: During revision surgery specimens derived from the fusion mass from 15 operations in 13 patients, who received spinal instrumentation and fusion in cervical, thoracic, and lumbar spine and addition of coralline hydroxyapatite. The age of patients at the time of revision surgery was 46 +/- 20 years. The time lapsed from the implantation of coralline hydroxyapatite and revision surgery was 11 +/- 9 months. The indication for revision surgery was infection, pseudarthrosis, technical error, and pain related to bulky hardware. The diagnosis for the primary fusion was degenerative disease, trauma and scoliosis, and the material of instrumentation used was composed from titanium alloy. The coralline hydroxyapatite was applied on the decorticated posterior elements of the instrumented spine. Material from ten different places from the fusion mass was intraoperatively taken in all patients and was sent for histological evaluation using the Hematoxylin-eosin histological stain technique and photomicroscope. RESULTS: Under photomicroscope there was a remarkable concentration of foreign-body like giant cells & development of inflammatory granulation tissue around hydroxyapatite, which was gradually replaced by dense connective collagen tissue. Both inflammatory granulation and collagen tissue showed areas with foreign body reaction. In the cases, where bone has developed, the most initial finding was the presence of osteoblasts & apposition of osteoid in contact to hydroxyapatite granules. In a later phase, cancellous and lamellar bone has developed as a result of secondary ossification. Bone formation was observed in 11/15 cases and was related with the patient's age in favor of young patients (R=0.56, P<0.05), while there was no correlation with time lapsed from operation. CONCLUSION: Coralline hydroxyapatite conducts bone formation in spine surgery because in the vast majority of the operated cases for different spinal disorders bone and osteoid has developed around the implanted coralline hydroxyapatite.

Adolescent↗

Performance and characterization of a nanophased porous hydroxyapatite for protein chromatography.

Nanophased porous hydroxyapatite beads with particle diameters of 25 microm and 30 microm intended for use in protein and biomolecule separation are characterized with respect to chromatographic characteristics. These particles were produced from a hydroxyapatite gel by a controlled spray process yielding microspheres containing hydroxyapatite nanocrystals. By calcification of the microspheres, nanophased porous hydroxyapatite beads were obtained. As a reference material, ceramic hydroxyapatite Types I and II with a particle diameter of 40 microm was chosen. SEM pictures show that the surface of the nanophased hydroxyapatite is very rough compared to ceramic hydroxyapatite Types I and Type II. The calcium-to-phosphorous ratio of this nanophased hydroxyapatite is 1.6, which is slightly below the theoretical ratio of 1.67 of pure hydroxyapatite. The porosity is greater than 60%. An IgG binding capacity of 60.7 mg/ml for Bio-Rad Type I and 36.0 mg/ml for Type II, 42.0 mg/ml for the nanophased material with 25 microm and 19.7 mg/ml for the nanophased material with 30 microm were observed. The nanophased material with 30 microm had the lowest mass transfer resistancy as indicated by the dependency of the dynamic binding capacity on velocity. It is assumed that the mass transport properties are characterized by a low particle diffusion resistancy or by slight intraparticle convection. The material also showed high selectivity for IgG. When culture supernatant with 5% FCS containing 3 mg/ml was loaded, pure IgG could be eluted by linear gradient with increasing sodium phosphate concentration. This nanophased material comprises a novel stationary phase for IgG separation.

Adsorption↗

Macroporous hydroxyapatite as alloplastic material for dental applications.

In the dentistry field, synthetic hydroxyapatite can be conveniently used as semiabsorbable alloplastic material to solve a number of clinical problems. The hydroxyapatite structure influences bone ingrowth as well as its resorption. In particular, pore size must exceed 100 microm to allow new bone ingrowth. Because of its brittleness, highly porous hydroxyapatite is difficult to handle without causing damage, and, therefore, its mechanical performance has to be improved placing the material on a dense hydroxyapatite substrate. Dense/porous hydroxyapatite laminates can be obtained by slip casting technology. The method starts with the preparation of a ceramic powder-binder-solvent system. This slurry produces, after solvent evaporation, a soft green tape, that is successively baked at 300 degrees C to remove all organic component, and finally sintered at high temperature (1200 degrees C). The material porosity cannot be significantly modified by changes in the slurry composition and sintering temperature; therefore, the macroporous hydroxyapatite layer must be obtained using a porous hydroxyapatite powder. The powder is prepared by grinding of green tape pieces and the resulting coarse material is successively baked at 300 degrees C. Such material is mixed with a polymer solution and cast on a green tape substrate. Layer fractures are not observed in both film bulks and interface, because during sintering the consolidation of two layers happens simultaneously. In the resulting material, the first layer consisted of macroporous hydroxyapatite with high osteoconductive properties, and the second layer was a dense hydroxyapatite substrate able to improve the laminate mechanical properties.

Journal Article↗

Osseointegration of hydroxyapatite porous-coated femoral implants in a canine model.

This study evaluated the quality and quantity of osseointegration of two thicknesses of hydroxyapatite coating on press-fit, porous-coated titanium implants in a canine hip model. In 12 dogs, titanium press-fit porous-coated prostheses were implanted. The stems had a 50-microm thickness hydroxyapatite coating, 100-microm thickness hydroxyapatite coating, or no hydroxyapatite coating. The animals were randomized into one of three groups and received one of the three implants. The implants were retrieved and examined 4 months after implantation. Direct juxtaposition of bone to the surface of the hydroxyapatite-coated implants with no intervening fibrous tissue layer was observed. There was no histologic evidence that hydroxyapatite initiated any foreign body reaction, nor was there any irregularity or resorption of the hydroxyapatite coating. There was a statistically significant greater degree of total bone apposition and bone ingrowth in the implants coated with hydroxyapatite at the level of the isthmus and the calcar. No statistical difference was found between the two groups with hydroxyapatite coatings in the degree of bone ingrowth or bone apposition.

Animals↗

Properties of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in the immature craniofacial skeleton.

Although extensive research regarding the treatment of calvarial defects has been done in adult models, little is known about the response in the maturing skeleton. The role of coralline hydroxyapatite and expanded polytetrafluoroethylene membrane in augmenting bone growth and repair of calvarial defects in a neonatal model is explored. Utilizing a 3-week-old neonatal swine model, bone growth into 28 calvarial defects was measured. After exposure of the calvaria in seven animals, four defects of 10 mm in diameter were created. In each animal, one defect was treated with a 10-mm disc of porous hydroxyapatite alone (Interpore 500, Interpore International), and a second defect was covered with an expanded polytetrafluoroethylene membrane (Gore-Tex OV-6) secured by four 3-mm microscrews (Luhr Microsystem, Howe-Medica Inc.). The third defect combined an implanted hydroxyapatite disc covered by an expanded polytetrafluoroethylene membrane, whereas the fourth defect served as an untreated control. Histology and histomorphometry were performed on undecalcified specimens harvested at 6 weeks after surgery. In both hydroxyapatite groups, the bone growth into the inorganic matrix provided complete osseous union in all specimens, and the amount of fibrosis was significantly lower (p < 0.02) in comparison with the control. Unexpectedly, there was significant osteoclastic resorption of the hydroxyapatite matrix (35.1 percent decrease) with simultaneous bone deposition and remodeling. The addition of an expanded polytetrafluoroethylene membrane covering the hydroxyapatite implant provided an insignificant advantage in bone growth (27.3 percent versus 28.3 percent, respectively). Finally, the expanded polytetrafluoroethylene membrane alone afforded no qualitative advantage secondary to intrusion of brain and dura into the defect as well as displacement of the membrane inward during appositional growth, leading to incomplete healing of the defect with thinning of the surrounding cranial bone. Unique in this maturing model was morphologic evidence of complete union at the calvaria-hydroxyapatite interface in all specimens as well as active remodeling of the hydroxyapatite matrix. The results of this study suggest that porous hydroxyapatite may be a suitable bone substitute in maturing calvarial bone defects, achieving superior osseous integration and volumetric bone gain while undergoing concurrent resorption and remodeling.

Animals↗

Biomechanical behavior of hydroxyapatite as bone substitute material in a loaded implant model. On the surface strain measurement and the maximum compression strength determination of material crash.

Many investigators have advocated that hydroxyapatite ceramics may be extremely prospective bone substitute material mainly through evidence with its given biocompatibility towards bone and demonstrated continuity between living bone and hydroxyapatite. Its mechanical brittleness and strength, however, have been the most serious considerations. In this paper, a study has been performed using animal experiments, massive hydroxyapatite ceramics are implanted into rectangular bone defect created by operation at the load-bearing area in close contact with tibia plateau. The changes of surface strain at the hydroxyapatite implantation of retrieved tibiae are measured at any week after implantation when the compressive stress were applied in the direction of long axis in order to clarify the mechanical behaviors of hydroxyapatite living bone complex. The compression strength of hydroxyapatite implant crash was also determined at each week after implantation. Results revealed that the hydroxyapatite living bone complex has been proven to have sufficient flexibility such that it shows no hysteresis in stress versus strain relationship up to 200 kg of applied load. The strain pattern on the surface of hydroxyapatite implant develops quite similar to that of natural cortical bone. The material crash of hydroxyapatite implant tolerates up to 500 kg of load at 52 weeks after implantation. These characteristics suggest that it achieves normal skeletal function in the points of biomechanical properties in vivo.

Animals↗

Hydroxyapatite in total hip arthroplasty. Clinical results and critical issues.

Surgeons who perform arthroplasties have posed some critical questions about hydroxyapatite. Does hydroxyapatite coating enhance bone ingrowth or ongrowth? Will hydroxyapatite lead to increased polyethylene wear or an increased incidence of osteolysis? Will the hydroxyapatite coating disappear, and if so, what will be left to maintain implant fixation? A multicenter study of 316 hips (282 patients) with a proximally hydroxyapatite coated stem and either a hydroxyapatite or porous coated cup were followed up 8.1 years (range, 5.6-9.9 years). The average patient age was 50 years (range, 16-81 years), and 61% of the patients were male. One (0.3%) stem, three (2.7%) porous coated cups, and 25 (11.9%) hydroxyapatite coated cups were revised for aseptic loosening. Disappointing results on the acetabular side indicate that substrate design is critical. There were no cases of intramedullary femoral osteolysis, and the incidence of acetabular and proximal femoral osteolysis- and polyethylene wear was no greater than that seen with other cementless or cemented components. Based on these clinical results and a critical review of the literature, it is concluded that hydroxyapatite coated hip components do enhance ingrowth or ongrowth with no increased incidence of osteolysis for as many as 10 years. Concern about the disappearance of the hydroxyapatite coating with time seems moot in light of the above clinical findings.

Adolescent↗