Hydroxyapatite Ceramic Implants Research Articles

Long-Bone-Regeneration Process in a Sheep Animal Model, Using Hydroxyapatite Ceramics Prepared by Tape-Casting Method.

This study was designed to investigate the effects of hydroxyapatite (HA) ceramic implants (HA cylinders, perforated HA plates, and nonperforated HA plates) on the healing of bone defects, addressing biocompatibility, biodegradability, osteoconductivity, osteoinductivity, and osteointegration with the surrounding bone tissue. The HA ceramic implants were prepared using the tape-casting method, which allows for shape variation in samples after packing HA paste into 3D-printed plastic forms. In vitro, the distribution and morphology of the MC3T3E1 cells grown on the test discs for 2 and 9 days were visualised with a fluorescent live/dead staining assay. The growth of the cell population was clearly visible on the entire ceramic surfaces and very good osteoblastic cell adhesion and proliferation was observed, with no dead cells detected. A sheep animal model was used to perform in vivo experiments with bone defects created on the metatarsal bones, where histological and immunohistochemical tissue analysis as well as X-ray and CT images were applied. After 6 months, all implants showed excellent biocompatibility with the surrounding bone tissue with no observed signs of inflammatory reaction. The histomorphological findings revealed bone growth immediately over and around the implants, indicating the excellent osteoconductivity of the HA ceramic implants. A number of islands of bone tissue were observed towards the centres of the HA cylinders. The highest degree of biodegradation, bioresorption, and new bone formation was observed in the group in which perforated HA plates were applied. The results of this study suggest that HA cylinders and HA plates may provide a promising material for the functional long-bone-defect reconstruction and further research.

Hydroxyapatite ceramic implants for cranioplasty in children: a retrospective evaluation of clinical outcome and osteointegration.

Cranioplasty in children is a controversial and challenging issue, since there is still no consensus on the ideal material. Main problems in paediatric age are represented by the child's growing skull, the lower bone thickness and the high incidence of cerebrospinal fluid (CSF) disorders or brain swelling. Autologous bone is still considered the "gold standard". When it is not available, a wide range of alloplastic materials have been proposed. Hydroxyapatite, a ceramic-based derivative, bears a chemical composition very similar to the human natural bone, making this material a valuable alternative to other cranioplasty solutions. All patients implanted with a custom-made porous hydroxyapatite device at Santobono-Pausilipon Hospital in Naples were retrospectively reviewed. A follow-up CT scan of the skull was performed from 1 up to 48months postoperatively to document the bone ingrowth as well as the osteointegration process. The bone density was measured as according to the Hounsfield scale at the bone-implant interface. Between 2014 and 2018, 11 patients (7 males, 4 females) underwent cranioplasty with hydroxyapatite ceramic implants (HAP). Patients' age ranged between 3 and 16years old. Initial aetiology was trauma in most cases. Two subjects were implanted with HAP as primary cranioplasty, 9 as revision surgery following previous cranioplasty failure. Sites of the cranial defect were unilateral fronto-temporo-parietal (N= 8), unilateral frontal (N= 1) and bifrontal (N= 2). Two patients with large bilateral defects received two prostheses. In one of these, the two prostheses were explanted and replaced with two back-up implants (accounting for a total of 15 implants in 11 patients). Osteointegration was measurable for 12 out of 15 implanted devices. The mean percentage was about 51%. There were six asymptomatic prosthesis fractures (40%), all occurring within 6months from implant. In one case, the bifrontal prostheses were explanted and replaced. This was the only patient who underwent revision surgery. Hydroxyapatite ceramic implants represent a valid alternative to other cranioplasty solutions. Where coaptation occurs correctly, with good osteointegration, implant mechanical resistance increases over time.

Hydroxyapatite ceramic implants for cranioplasty in children: a single-center experience

The use of hydroxyapatite ceramic (HAC) implants for the treatment of skull defects in pediatric patients started 2010 at our institution. Ceramic implants facilitate osteoblast migration and therefore optimize osteointegration with the host bone. The purpose of this study is to report a single-center experience with this treatment modality. A retrospective review of all patients from July 2010 through June 2014 undergoing a cranioplasty using hydroxyapatite ceramic implant and managed at a single institution was performed. Indication for cranioplasty, the hospital course, and follow-up were reviewed. Bone density was measured in Hounsfield Units (HU) and osteointegration was calculated using Mimics Software® (Mimics Innovation Suite v17.0 Medical, Materialize, Leuven, Belgium). Over the 4-year period, six patients met criteria for the study. Five patients had an osteointegration of nearly 100%. One patient had an incomplete osteointegration with a total bone-implant contact area of 69%. The mean bone density was 2800 HU (2300-3000 HU). Bone density alone is estimated to have a Hounsfield value between 400 and 2000 HU depending on the body region and bone quality. There were no major complications, and the patients were highly satisfied with the esthetical result. Hydroxyapatite ceramic implants for cranioplasty in pediatric patients are a good choice for different indications. The implants show excellent osteointegration and esthetical results.

Assessment of the RIVET fixation system for cranioplasty using the pull-out technique

Cranioplasty using custom-made hydroxyapatite (HAP) ceramic implants is a common procedure to repair skull defects. However, commercially available titanium screws are only minimally stabilized due to characteristic brittleness. We developed the RIVET technique which involves fixing a bioabsorbable plate atop a HAP block using bioabsorbable screws extending beyond both layers, and evaluated fixation strength using the pull-out test and microtomography. Three experimental conditions were compared: a non-RIVET group, RIVET group, and dry skull control group. Pull-out strength significantly differed across groups (non-RIVET group, 1.33 ± 1.21 kgf; RIVET group, 4.46 ± 0.84 kgf; and control group, 6.99 ± 1.14 kgf, P < 0.01). Microtomography of the dry skull control group revealed thread grooves fitted to the screws. The non-RIVET and RIVET groups presented fewer thread grooves than the control group, and the screws did not fit perfectly to the HAP block. However, fixation in the RIVET group was more stable, as the rivet was firmly lodged into the implant. In conclusion, by melting and creating the rivet, pull-out strength can be increased and rigid stabilization of HAP can be obtained. This technique uses commercially available absorbable plate and screws, and thus can be used widely in clinical applications involving HAP blocks with different porosities and thicknesses.

The RIVET

Cranioplasty using custom-made hydroxyapatite (HAP) ceramic implants is a common procedure for the repair of skull defects. The advantages of using HAP are that it is nonmetallic, unlike titanium; biocompatible; and osteoconductive. Furthermore, it can be molded to any complex shape that may be needed. A disadvantage is that titanium screws and plates are in development for its fixation. We developed a technique for implant fixation using bioabsorbable screws and plates, and named this technique RIVET: resorbable immobilization for vacuolar en bloc technique.Before each operation, the implant was customized for the patient in question on the basis of models prepared using computed tomography data. The bioabsorbable plates were attached to the implant by drilling, tapping, and screwing, as shown in the video (http://links.lww.com/SCS/A43). The interior portion of the screw was then melted to flatten it against the internal surface of the implant, forming a rivet to join the plate and HAP implant.We used this technique for cranial reconstruction in 2 patients, with satisfying and functional results. We did not encounter any complications.In conclusion, the technique described here allows surgeons to fix implants and plates together more rigidly, giving a better result than possible with previous methods.

Reaction of Subcutaneous Connective Tissue of Experimental Animals on Bone Marrow Mesenchymal Stromal Cell Coated Hydroxyapatite

Summary Introduction. Hydroxyapatite (HAp) scaffolds have become an alternative to autologous bone grafts in orthopedic surgery, because it is possible to fill larger scale bone defects and of the decreased operation time and complication risks at the graft donor site, a promising method in bone regeneration is to load bone marrow - mesenchymal stromal cells (BM-MSCs) on to a HAp scaffold. Aim of the Study. The aim of our study is to compare subcutaneous tissue reaction of experimental animals to implantation of HAp and HAp that is coated with BM-MSCs. Materials and Methods. Autologous BM-MSCs were cultivated from crista iliaca dextra biopsy, 4 HAp ceramic implants were coated with BM-MSC and implanted in subcutaneous tissue on one side and non-coated HAp implants on the other side of the spine of 4 rabbits. Immunohistochemical staining of BM-MSC and connective tissue included TUNEL assay, NFkBp105, HSP 70k, Wnt1, TNF-α, VEGF, MMP-2 antibodies, microscoped at 400X magnification and analyzed semiquantitatively. Results. Routine staining with haemotoxilin and eosin demonstrated formation of granulation tissue around the HAp implant, which was more distinct on the control side. There was an increased number of NFκB p105 positive cells (fibroblasts, myocytes, endotheliocytes) on the experimental side (+++), in comparison to the control side (++). HSP70 and apoptosis index was decreased on the experimental side (++ and 60%), in comparison to the control side (+++ and 70%). Number of MMP2 positive structures was increased on the control side in the fibrous capsule (++), in comparison to the experimental side, where the result varied (0 - +) Conclusions. Cultured BM-MSC activity is partly limited due to the apoptosis, which is probably induced by environmental factors. BM-MSC coated HAp implant stimulates secretion of proliferation marker NFkBp105 in subcutaneous tissue, decreases cell stress, apoptosis and tissue degradation (decreased HSP 70, apoptotic cell count and MMP 2) to improve the local tissue quality and proving BM-MSC tissue protective effect

Porous Hydroxyapatite and Aluminium-Oxide Ceramic Orbital Implant Evaluation Using CBCT Scanning: A Method forIn VivoPorous Structure Evaluation and Monitoring

Objective. This study aimed to define CBCT as a technique for postimplantation in vivo examination of porous hydroxyapatite and aluminium-oxide orbital implant shape, volume and density changes. Methods and Materials. CBCT was used to evaluate 30 enucleated patients treated with spherical polyglactin 910 wrapped hydroxyapatite and aluminum-oxide orbital implants. The mean duration of patient followup was 3.2 years or 1338 days with a range of 0.2 to 7.2 years or 79 to 2636 days in a population with an average age of 40.8 years. Results. The resolution of currently clinically used CBCT equipment allowed detailed structural observation of the orbital hydroxyapatite implants with some modifications. Volume and shape estimations were possible while density evaluation was more complicated compared to medical source computed tomography. The mean densities of the orbital implants were followed and a consistent gradual decrease identified from the beginning of implantation which was better defined after the applied correction procedure. Conclusion. CBCT with lower dosages of radiation exposure can be used to follow changes in implanted high-density porous structures. The density evaluation is possible with calibration modifications. Changes in orbital implant densities identified in this study may correspond to healing and maturation of soft tissues surrounding and penetrating the implants.

Reinforcing of Porous Hydroxyapatite Ceramics with Hydroxyapatite Fibres for Enhanced Bone Tissue Engineering

Porous hydroxyapatite (HA) ceramic implants have attracted attention in bone tissue engineering due to their excellent bioactivity and biocompatibility due to their chemical similarity with the mineral component of natural bone. Unfortunately, HA when is formed into porous structures exhibits very low compression strength. In this study, fabrication of porous HA ceramic scaffolds containing HA fibers is presented. The primary aim of the study is to improve mechanical properties of the scaffold by introducing the fiber with uniform component relative to the scaffold. Scanning electron microscopy was used to observe the surface morphology and pore size of the scaffold. X-ray diffraction (XRD) was used to detect the phase composition and crystallinity of the scaffold. The compressive strength was determined using a universal material test machine. The results and the characterizations demonstrate the addition of HA fiber could enhance the uniformity of mechanical properties among samples and also the strength for a given open porosity.

Treatment for infected total knee arthroplasty using calcium hydroxyapatite ceramic implants impregnated with antibiotic

Treatment for infected total knee arthroplasty using calcium hydroxyapatite ceramic implants impregnated with antibiotic

DRUG INFILTRATION IN POROUS HYDROXYAPATITE CERAMIC AND TISSUE RESPONSE

ABSTRACT Sintered porous hydroxyapatite (HAp) ceramics were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), optical and scanning electron microscopy (SEM). The samples were saturated with dexamethasone solution (1 mg/ml) or lidocaine solution (5 mg/ml) using vacuum method. To evaluate early reactogenity of porous synthetic impregnated HAp ceramic implants were inserted in holes of rabbit's lower jaws for 2 weeks, 1 month and 3 months. Immunohistochemical methods for evaluation of growth factors and apoptosis were applied. This study aims to further comprehension of reactogenicity of HAp bioceramic implants as bone substitutes in subperiostal environment.

Enhancement of bone formation in hydroxyapatite implants by rhBMP‐2 coating

The combination of hydroxyapatite (HA) implants serving as osteoconductive scaffold with growth factors is an interesting approach for the improvement of bone defect healing. The purpose of this study was to test whether recombinant human bone morphogenetic protein-2 (rhBMP-2) coating of solid HA-implants improves bone formation in a cortical bone defect. Cylindrical trephine mill defects (diameter: 9.8 mm, depth: 10 mm) were created into the cortical tibia shaft of minipigs and subsequently filled either by plain HA cylinders (Endobon) or by rhBMP-2-coated HA cylinders. Fluorochrome labeling for the evaluation of time-dependent bone formation was done on days 8, 9, and 10 postsurgery with tetracyclin-100, at days 25 and 30 with alizarin-komplexon, and finally on days 32, 37, 73, and 79 with calcein green. Twelve weeks after implantation, the tibiae were harvested and were prepared for standard histological staining, fluorochrome analysis, and histomorphometry. Coating of HA implants with rhBMP-2 led to significant enhanced new bone formation of 84.7% (+/-4.6%) of the implant area with almost complete bony incorporation compared with only 27.7% (+/-8.5%) in the uncoated HA implants (p = 0.028). In both types of implants, osteoconduction of HA led to bone ingrowth of the surrounding host bone into the implants. However, only rhBMP-2-coated implants showed multitopic de novo bone formation reflecting the osteoinductive properties of rhBMP-2 in all areas of the HA implant. This study showed that the coating of HA ceramic implants with rhBMP-2 can significantly enhance new bone formation attributable to its osteoinductive effects.

Tailor-made orbitocranioplasty for a sphenorbital encephalocele presenting as pulsatile exophthalmos

Basal encephaloceles account for only 1.5% of all encephaloceles. Within this group, the sphenorbital type is quite rare but causes herniation of the brain into the orbit, leading to pulsatile exophthalmos and disturbance of visual acuity. The authors present a case of successful orbitocranioplasty for a sphenorbital encephalocele in which they used a skull model in preparation for the operation. A plaster skull model was made from 3D computed tomography (CT) data obtained in a 6-year-old girl with a sphenorbital encephalocele to determine the appropriate size and shape of an implant for repair of the malformation. A hydroxyapatite ceramic implant with high affinity to autologous bone was designed to cover the defect and simultaneously to enlarge the volume of the orbit as well as allow rigid fixation. Postoperative 3D CT scanning demonstrated good placement of the implant, and the patient's pulsatile exophthalmos diminished immediately. The patient's postoperative condition has been good, and she has exhibited no neurological deficit or deformity of the skull around the cranioplasty 30 months after the operation. A skull model using 3D CT data is useful for determining the most appropriate strategy for reconstruction. Hydroxyapatite ceramic implants have high affinity to autologous bone and thus are suitable for children. In cases such as the present one, however, the patient should be observed carefully to ensure that there is not an imbalance between the implant and the still growing autologous skull.

Glycerol- l-lactide coating polymer leads to delay in bone ingrowth in hydroxyapatite implants

Glycerol- l-lactide as coating polymer for the delivery of basic fibroblast growth factor (bFGF) from hydroxyapatite (HA) ceramic implants was shown to lead to significant delay in bone ingrowth into the implants compared to implants without the coating polymer. The purpose of this work was to study bone ingrowth in HA ceramic implants with and without the coating polymer but without growth factors to enable differentiation between a locking effect of the pores by the polymer and the fact of inactivation of the growth factors by the polymer, which could both be possible for the delay. A defect was created in the subchondral region of both femurs in 24 miniature-pigs and was either filled by the HA implants with or without the coating polymer. Histomorphometry showed a significant delay in bone ingrowth in the polymer coated implants both after 6 and 12 weeks. Detailed histology revealed that the HA pores were completely “locked” by the polymer leading to complete loss of the osteoconductive properties of the HA. Also electron microscopy showed filling of the HA pores by the polymer. Therefore, it can be concluded that glycerol- l-lactide should not be used to coat HA ceramic implants due to significant delay in bone ingrowth.

Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic.

To evaluate the growth/differentiation factor-5 (GDF-5) in the in vivo osteogenic potential of bone marrow mesenchymal stem cells (MSCs), we subcutaneously implanted five different kinds of hydroxyapatite (HA) ceramic implants: HA alone, GDF-5/HA composites (GDF/HA), MSCs/HA composites, the MSCs/HA composites supplemented with GDF-5 (GDF/MSCs/HA), and recombinant bone morphogenetic protein-2 (BMP/MSCs/HA). Neither the HA alone nor the GDF/HA composites exhibited any bone formation at any time after implantation. At 4 weeks, the MSCs/HA composites exhibited a certain amount of bone formation in some pore areas. In contrast, at 2 weeks, the GDF/MSCs/HA composites exhibited histologically obvious de novo bone formation together with active osteoblasts in many pore areas and additional bone formation at 4 weeks. In the de novo formed bone, neither chondrocytes nor endochondral bone was detected. The GDF/MSCs/HA composites also showed high alkaline phosphatase (ALP) and osteocalcin expression determined at both the protein and gene levels and the high level of expression was well maintained even at 4 weeks. Compared with GDF/MSCs/HA, the BMP/MSCs/HA composites exhibited excellent osteogenesis with relatively early osteoblastic phenotype expression. The results indicate that GDF-5 synergistically enhances de novo bone formation capability of MSCs/HA composite and suggest that tissue-engineered GDF/MSCs/HA composites could be used as bone graft substitutes.

Bone ingrowth in bFGF-coated hydroxyapatite ceramic implants

This experimental study was performed to evaluate angiogenesis, bone formation, and bone ingrowth in response to osteoinductive implants of bovine-derived hydroxyapatite (HA) ceramics either uncoated or coated with basic fibroblast growth factor (bFGF) in miniature pigs. A cylindrical bone defect was created in both femur condyles of 24 miniature pigs using a saline coated trephine. Sixteen of the 48 defects were filled with HA cylinders coated with 50 μg rhbFG, uncoated HA cylinders, and with autogenous transplants, respectively. Fluorochrome labelled histological analysis, histomorphometry, and scanning electron microscopy were performed to study angiogenesis, bone formation and bone ingrowth. Complete bone ingrowth into bFGF-coated HA implants and autografts was seen after 34 days compared to 80 days in the uncoated HA group. Active ring-shaped areas of fluorochrome labelled bone deposition with dynamic bone remodelling were found in all cylinders. New vessels could be found in all cylinders. Histomorphometric analysis showed no difference in bone ingrowth over time between autogenous transplants and bFGF-coated HA implants. The current experimental study revealed comparable results of bFGF-coated HA implants and autogenous grafts regarding angiogenesis, bone synthesis and bone ingrowth.

Histological Evaluation of an 11-year-old Hydroxyapatite Ceramic Implant in Mandibular Bone

There are no detailed long-term histological studies of hydroxyapatite implanted in human bone tissue. This report is of histological and radiographic examination of a patient with mandibular bone implanted with hydroxyapatite ceramics after cyst ennucleation and a good clinical course for 10 years. The mandibular bone was resected 11 years after the initial operation because of infection. Histology of the retrieved mandibular bone revealed that bone tissue proliferated into interparticular spaces and attached to the hydroxyapatite ceramics surfaces in the non-infected portion and that hydroxyapatite ceramics disappeared with bone destruction in the infected portion. From the histological results, clinical findings, and chronological radiographic findings for 10 years, it was concluded that hydroxyapatite ceramics could maintain their favourable properties as a bone substitute in human bone for a long time.

Treatment of infected total hip arthroplasty due to Methicillin-resistant Staphylococcus aureus using calcium hydroxyapatite ceramic implants impregnated with antibiotic

Treatment of infected total hip arthroplasty due to Methicillin-resistant Staphylococcus aureus using calcium hydroxyapatite ceramic implants impregnated with antibiotic

Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog

Bone induction by different calcium phosphate biomaterials has been reported previously. With regard to (1) whether the induced bone would disappear with time due to the absence of mechanical stresses and (2) whether this heterotopically formed bone would give rise to uncontrolled growth, a long-time investigation of porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic (TCP/HA, BCP), porous α-tricalcium phosphate ceramic ( α-TCP) and porous β-tricalcium phosphate ceramic ( β-TCP) was performed in dorsal muscles of dog, for 2.5 years. Histological observation, backscattered scanning electron microscopy observation and histomorphometric analysis were made on thin un-decalcified sections of retrieved samples. Normal compact bone with bone marrow was found in all HA implants ( n=4) and in all BCP implants ( n=4), 48±4% pore area was filled with bone in HA implants and 41±2% in BCP implants. Bone-like tissue, which was a mineralised bone matrix with osteocytes but lacked osteoblasts and bone marrow, was found in all β-TCP implants ( n=4) and in one of the four α-TCP implants. Both normal bone and bone-like tissues were confined inside the pores of the implants. The results show that calcium phosphate ceramics are osteoinductive in muscles of dogs. Although the quality and quantity varied among different ceramics, the induced bone in both HA and BCP ceramics did neither disappear nor grow uncontrollably during the period as long as 2.5 years.

Evaluation of a high density polyethylene fixing system for hydroxyapatite ceramic implants.

A fixing system made of high density polyethylene (mini ROC fastener system, Innovasive Devices Inc., Marlborough, MA, USA) was applied to artificially porous hydroxyapatite (HAP) implants. Their fixing ability was assessed with pull-out tests and a preliminary study was done to determine the most suitable drill hole diameter and depth. Effectiveness of the combined use of drill-free titanium screws (Martin GmbH & Co. Ltd., Tuttlingen, Germany) and the mini ROC fastener system was also evaluated. The pull-out strength of the system differed according to the hole diameter and depth of insertion. The strongest physical strength was obtained with holes 2.10 mm in diameter and 6 mm in depth. If inserted under optimum conditions, the mini ROC fastener system was deemed to have adequate fixing ability for clinical applications pull-out strength more than 7 kgf. In addition, the combined use of a drill-free screw for microplate with the mini ROC fastener system had a pull-out strength of around 10 kgf which was superior to the mini ROC fastener system alone. The mini ROC fastener system is best suited to fix HAP implants to the soft tissues such as muscle, tendon or periosteal tissue as well as for plate fixation when used with drill-free screws. The fact that effective fixing was achieved should result in a further increase in the clinical use of artificial HAP implants.

Osteoconduction in large macroporous hydroxyapatite ceramic implants: evidence for a complementary integration and disintegration mechanism

Large, cylindrical implants of a porous calcium phosphate ceramic (“hydroxyapatite” starting material, HAC) were used to replace far greater than critical-sized sections of the midshaft of sheep tibiae and retrieved at 2 and 9 months; external fixation was used in the first 5 months. Excellent clinical function of these implants was reported in a previous study. The material retrieved was embedded in PMMA, and blocks were sectioned and surfaces were polished and carbon coated prior to study using digital backscattered electron (BSE) imaging. Detailed scanning electron microscopy study of the pattern of osseointegration of the implanted material at early (2 months) and late (9 months) timepoints revealed a previously unrecognized pattern of integration/disintegration of this implant material in tandem with bone growth. We conclude that bone adaptation to the HAC leads to its fracture and that the newly generated surfaces are equally osteoconductive. This leads to a self-propagating, self-annealing system in which defects in the HAC are mended by intercalation of bone.