Ceramics have many properties which might make them suitable alternatives to bone grafts. This present study was done to find a suitable biodegradable porous ceramic for human bone replacement. Three different porous ceramics (calcium aluminate, calcium hydroxyapatite and tricalcium phosphate), with interlinked pores of two size ranges (150 to 210 micron), were implanted into the skulls of rats and rabbits for up to six months; the interaction with surrounding bone, which is virtually devoid of bone marrow, was then assessed. The ceramics caused no adverse biological response. Tissue ingrowth into pores throughout the implant was seen in all three types and in both pore sizes of ceramic, but the density of the penetrating tissue was far less for calcium aluminate than for calcium hydroxyapatite or tricalcium phosphate. For each type of ceramic, the soft-tissue ingrowth was more dense with the larger pore size, and with a longer period of implantation. Bone ingrowth was not usually seen within the pores of any ceramic. There were no differences in the histological findings between the rats and the rabbits. The results demonstrate that it is possible to produce ceramic materials with a porous structure which allows ingrowth of tissue and biological fluids

While high-performance ceramics like alumina and zirconia exhibit excellent wear resistance, they provide poor osseointegration capacity. As osseointegration is crucial for non-cemented joint prostheses, new techniques have been successfully developed for biofunctionalizing high-performance ceramic surfaces. Stable cell adhesion can be achieved by covalently bound specific peptides. In this study we investigate the effect of sterilization processes on organo-chemically functionalized surfaces. To enhance the performance of alumina-toughened zirconia ceramics (ATZ), a 3-aminopropyldiisopropylethoxysilane (APDS) monolayer was applied and coupled with cyclo-RGD peptides (cRGD) by using bifunctional crosslinker bis(sulfosuccinimidyl)suberat (BS³). The samples were sterilized using e-beam or gamma-sterilization at 25 kGy, either before or after biofunctionalization with cRGD. Functionalization stability was investigated by contact angle measurements. The functionality of cRGD after sterilization was demonstrated using proliferation tests and cytotoxicity assays. Immunofluorescence staining (pFAK, Actin, DAPI) was conducted to evaluate the adhesion potential between the samples and human mesenchymal stem cells (hMSCs). Functionalized samples before and after sterilization showed no significant difference regarding their contact angles. A proliferation test demonstrated that the cells on functionalized samples proliferate significantly more than on untreated samples before and after sterilization. hMSCs showed a significant higher proliferation on gamma sterilized samples compared to all other groups after 14 days. It was confirmed that the samples did not exhibit cytotoxic behavior before or after sterilization. Fluorescence microscopy demonstrated that both, cells on sterilized and on non-sterilized samples, expressed high levels of pFAK-Y397. The investigated functionalization enables improved adhesion and proliferation of hMSCs and is stable against the investigated sterilization processes. This is of importance as the option of having a sterile product enables the start of the translation of this biofunctional coating towards preclinical and subsequently first-in-man applications. Acknowledgments: We acknowledge the financial support of the Federal Ministry of Education and Research, BMBF (13GW0452A-C)

Biomaterials improve the quality of life for an ever increasing number of people each year. The range of applications is vast and includes such things as joint and limb replacements, artificial arteries and skin, contact lenses and dentures. Ceramic biomaterials can be divided roughly into three main types governed by their in vivo behaviour and tissue response. In broad terms, there are the bioresorbable ceramics (b-tricalciumphosphate), bioreactive (hydroxyapatite, fluorapatite and bioglass) and bioinert (alumina, zirconia and pyrolytic carbon). The resorbable ones are incorporated into the surrounding tissue, or may even dissolve completely over a period of time. The bioreactive ones, like hydroxyapatite (used for coatings on metallic pins), encourage bonding to surrounding tissue with, for example, new bone growth being stimulated. The bionert ceramics are mostly used for structural components. Alumina and Zirconia are known for their general chemical inertness and hardness. These properties are exploited for implant purposes, where they are used as an articulating surface in hip and knee joints. Their ability to be polished to a high surface finish make them an ideal candidate for this wear application, where they operate against materials such as ultra high molecular weight polyethylene (UHMWPE). Alumina is a highly inert material and resistant to most corrosive environments, including the highly dynamic environment that is the human body. Under physiological conditions, it is classed as nearly inert, with evidence of any response from surrounding tissues and remaining essentially unchanged after many tyears of service. However, the body does recognise it as a foreign material and does attempt to isolate it by forming a layer of non adherent fibrous tissue around the implant where possible. Porous alumina may also be used to replace large sections of bone that have been removed for reasons such as cancer. Alumina has been used in dental applications. Specifically, it has been used for tooth replacements. The term high alumina ceramics is referred to materials that have the minimal content of 97% of alumina. If the percentage of minimal alumina is of 99% it is called high purity alumina ceramics. In its α phase (better famous like corundum), characterized from its particular structure and stability, the high purity alumina is used in orthopaedics, in the articulations of the hip and knee prostheses. From more than 30 years, the alumina has been successfully used. Today, more than 3,5 million of ball-heads e and 350 thousand of inserts of alumina BIOLOXA8 have been implanted confirming, in clinical use, the characteristics of low wear and biocompatibility that has allowed to reduce the problems of osteolisis induced by the polyethylene. The increase of the mechanical characteristics, the new shapes and the conical fixation have raised the reliability of the ball-heads and inserts of alumina. The BIOLOXA8forte (in commerce from 1994) is an high purity alumina (ca 99,7 %) with a small percentage of magnesium oxide (MgO). Approximately 50 years ago, magnesium oxide was introduced in the phase of sintering of the alumina, because it was discovered that a small amount of this additive prevented the increase of grains of alumina during the sintering process. It was therefore possible to have a more homogenous and dense microstructure, both characteristic directly correlated with the mechanical resistance. The suffix ‘forte’ derives from the increased mechanical characteristic caught up with the continuous optimization of the fabrication technology. Many laboratory tests and clinical cases have shown that the wear rate of alumina-alumina bearing coupling is extremely low (0.001 mm/year). If compared with metal-polyethylene (0,2 mm/year), it evidences the drastic reduction of particles of debris and therefore of the osteolysis problem. One of the main factors that the reduction of the wear rate involves is the characteristic molecular structure of alumina. Its superficial layer is composed of oxygen atoms that create a residual electric power which interacts with polarized molecules of the lubricant, binding it to the surface by strong Van der Waals ties. It is therefore guaranteed the presence of a fluid film that reduces the coefficient of clutch between the two surfaces involved during the articulation. The colour of alumina components is subjected to variations. Originally it is ivory, but it can easy stretch to the brown after sterilization with gamma beams that interact with the free valences introduced by the MgO. This change of colour does not induce changes of the mechanical characteristics. Currently the systems are completely modular and allow a wide choice of couplings. Ceramic acetabulum has been abandoned and replaced by ceramic inserts. In 1984 and subsequently in 1995, the introduction of ISO standards for the production of ceramics ball-heads and inserts and the concept of conical fixation has allowed to catch up higher reliability. The third generation of alumina has reduced the complications rates to values around 0.01% (for the 28 mm ball-heads and inserts), maintaining the excellent tribology and wear characteristics. Today, the alumina BIOLOXA8forte components are prepared in clean-room, sintered with high quality control processes, marked by laser and accurately inspected and tested. The dimension of grains of the microstructure, currently reduced to inferior values of 2 B5m, has allowed to raise the value of the mechanical resistance of about 45% (580 Mpa) of the value requested by ISO standard (400 Mpa). The tolerances between ceramics (ball-heads and inserts) and metallic parts (taper and metal shell) are fundamental for lengthening the implant reliability. It is important to control and certificate the stems and cups which the ceramic parts are applied on. Correct assembling and the respect of the compatibilities between parts (angle, material, producer) guarantee the longevity of the implants. Actually, in the orthopaedic field, the alumina application is mainly used in standard applications of the hip prostheses. Ball-heads of 22 milimeters of diameter, lengths of neck type XL, and the knee prostheses are not possible because of the mechanical characteristics of alumina not allowing to catch up the elevate stress values requested for these special applications. Between 1975 and 1977, the first studies issued that the strenght of alumina could be reinforced by the introduction of ceramic oxides. It was discovered that the strenght and toughness of alumina could endure a remarkable increment through the realization of composites with oxide of zirconium (zirconia). In the zirconia, during the phase of cooling from temperatures over 1170A1C, the grains endure a change of phase (from tetragonal to monoclinic), with an increase of 3% of volume. At ambient temperature the phase monoclina is stable. This transformation is martensitic, with energy absorption, and involves a heat-proof change of the simmetry of the structure. In the case of dispersed grains of zirconia in the alumina matrix, the transformation absorbs the energy of the crack and the tenacity of the ceramics increases. The Yttria (Y2O3) use, as stabilizing of the zirconia, has allowed to exceed the problem of the defects of the structure. It was introduced a percentage of zirconia stabilized with yttria (Y-TZP) in the alumina matrix and other mixed oxides to counterbalance the reduction of the hardness caused by particles of zirconia and to create lengthened particles during the sintering. All this studies have been used to create the new ceramics BIOLOXA8delta. Tests of biocompatibility in agreement with norms EN 30993 have been carried out allowing the implants of these new composite ceramics. The BIOLOXA8delta has a bending strenght around 1000 MPa, that is more than the double of the alumina standard (400 MPa). In the minimum fracture load test, ball-heads of 28 mm AF millimeter (neck L) have caught up values around 100 KN, very beyond the 46 KN requested by the FDA. Multiple cycles of sterilization in autoclaves have demonstrated that the BIOLOXA8delta does not endure alterations of the mechanical and tribological characteristics. On the basis of these results, BIOLOXA8delta will allow the realization of medical ceramics devices, already in study phase, like knee prosthesis, 22 mm ball-heads, thinner wallthickness of inserts, whose realization was not possible with the ceramic materials up to now available

CaSiO3 has been used a potential bioactive material for bone regeneration. A drawback of the CaSiO3 ceramics is that they possess high dissolution rate of Ca ions leading to a high pH value environment [1], which can disadvantage cell growth. Zn can enhance osteoconductivity of CaP ceramics and stimulate bone formation [2]. The aims of this study are:. In situ preparation and optimization of Zn-CaSiO3 ceramics by the evaluating of physical and chemical properties, osteoblast and osteoclast behavior;. Sol-gel coating the optimized hardystonite (HT, Ca2ZnSi2O7) on Ti-6Al-4V. Zn-CaSiO3 ceramics containing zero, ten, 20 and 50-mol% of Zn were sintered at 1260 °C. The dissolution and apatite formation ability were evaluated by soaking in simulated body fluids. Attachment, proliferation and differentiation of human primary bone-derived cells (HBDC) on ceramic disks were evaluated. Human monocytes isolated from buffy coats were differentiated into mature and functional osteoclast (OC) by culturing them for 21 days on ceramic disks. Then, the optimized HT (50%Zn-CaSiO3) coating on Ti-6Al-4V was prepared by sol-gel spinning method. The incorporation of Zn in CaSiO3 resulted in part of new phase formation (HT) formation in Zn-Ca-Si ceramics. When adding 50 mol% of Zn, only pure HT phase existed. The incorporation of Zn in CaSiO3 decreased the dissolution and pure 50 mol% of Zn (HT ceramics) resulted in the lowest dissolution. Zn-CaSiO3 ceramics with different Zn contents supported HBDC attachment. With the increase of Zn contents, HBDC proliferation and differentiation improved. The surface roughness of Sol-gel HT coating is about 0.49 μm. The thickness of coating is about 1 μm. HT coating has a similar dissolution kinetics and stability with hydroxyapatite coating. Zn decreases the dissolution in Zn-Ca-Si ceramics and enhances HBDC proliferation and differentiation. The optimized HT ceramics (50mol% Zn) support OC resorption and can be used for a stable biomedical coating application

Alumina and zirconia are known for their general chemical inertness and hardness. These properties are exploited for implant purposes, where they are used as an articulating surface in hip and knee joints. Their ability to be polished to a high surface finish make them an ideal candidate for such wear applications, where they compete against materials such as ultra-high-molecular-weight polyethylene. Alumina is a highly inert material and resistant to most corrosive environments. The term high alumina ceramics refersr to materials that have a minimal content of 97% of alumina. If there is a 99% minimal percentage of alumina it is called high purity alumina ceramics. In its _ phase (more famous than corundum), characterised by its particular structure and stability, high purity alumina has been being used in orthopaedics since 1970, in the articulations of the hip prostheses. BIOLOX. ®. forte (commercially available since 1994) is high purity alumina (ca 99.7 %) with a small percentage of magnesium oxide (MgO). Approximately 50 years ago, MgO was introduced during the sintering phase of alumina because it was discovered that a small amount of this additive prevented the increase in grains of alumina during the sintering process. It was therefore possible to have a more homogenous and dense microstructure; both characteristics directly correlated with the mechanical resistance. The suffix forte derives from the increased mechanical characteristic and continuous optimisation of the fabrication technology. One of the main factors involved in wear reduction is the characteristic molecular structure of alumina. Its superficial layer is composed of oxygen atoms that create a residual electric power which interacts with polarized molecules of the lubricant, tying it to the surface by strong Van der Waals ties. Therefore the presence of a fluid film that reduces the coefficient of clutch between the two surfaces involved during the articulation is guaranteed. The colour of alumina components varies. Originally it is ivory, but it can easily become brown after sterilization with gamma beams that interact with the free valences introduced by the MgO. This change in colour does not change the mechanical characteristics. Currently the systems are completely modular and allow a wide choice of couplings. In 1984 and subsequently in 1995, the introduction of ISO norms for the production of ceramics ball-heads and inserts and the concept of conical fixation has provided higher reliability. Today, the alumina BIOLOX. ®. forte components are prepared in clean-rooms, sintered with high quality control processes, laser marked and accurately inspected and tested. The tolerances between ceramics (ball-heads and inserts) and metallic parts (taper and metal shell) are fundamental for increasing implant reliability. It is important to control and validate the stems and cups which the ceramic parts are applied on. Correct assembly and the respect of the compatibilities between parts (angle, material, producer) guarantee the longevity of the implants. Actually, in the orthopaedic field, alumina is mainly used in standard applications of hip prostheses. Ball-heads of 22 mm in diameter, lengths of neck type XL, and the knee prostheses are not possible because the mechanical characteristics of alumina do not allow for the elevated stress values requested for these special applications. Between 1975 and 1977, it was discovered that the strength and toughness of alumina could endure a remarkable increment by developing composites with oxide of zirconium (zirconia). In zirconia, during the phase of cooling from temperatures over 1170°C, the grains go through a change of phase (from tetragonal to monoclica), with an increase of 3% of volume. At ambient temperatures the monoclica phase is stable. This transformation is martensitic, with energy absorption, and involves a heat-proof change of the symmetry of the structure. In the case of dispersed grains of zirconia in the alumina matrix, the transformation absorbs the energy of the crack and the strength of the ceramics increases. With the use of yttria (Y. 2. O. 3. ) to stabilise the zirconia the problem of the structure defects can be resolved. A percentage of zirconia stabilized with yttria (Y-TZP) was introduced in the alumina matrix and other mixed oxides to counterbalance the reduction of the hardness caused by particles of zirconia and to create lengthened particles during the sintering. All these studies have been used to create the new ceramic BIOLOX. ®. delta. Tests of biocompatibility in agreement with norms EN 30993 have been carried out, so that implants can be made of these new composite ceramics. Since 1970, more than 3,500,000 ball-heads and 350,000 inserts of alumina BIOLOX. ®. have been implanted. Owing to the grain size, currently reduced to values under 2 μm, the value of the mechanical resistance has been raised to about 580 MPa. The increase in the mechanical characteristics, the new shapes and the conical fixation have reduced the risk of fracture of the BIOLOX. ®. forte ball-heads and inserts to around 0.01% (Ø28 mm), maintaining the excellent tribology and wear characteristics. Many laboratory tests and clinical cases have shown that the wear rate of the alumina-alumina bearing complex is extremely low (0.001 mm/year). If compared with metal-polyethylene (0.2 mm/year) it shows a drastic reduction of particles of debris and therefore of the osteolysis problem. BIOLOX. ®. delta has a bending strength of around 1000 MPa, which is more than double that of the alumina ISO (400 MPa). In the minimum fracture load test, ball-heads of 28 mm Ø millimeter (neck L) have achieved values of around 100 KN, well beyond the 46 KN requested by the FDA. Multiple cycles of sterilisation in autoclaves have demonstrated that the the mechanical and tribological characteristics of BIOLOX. ®. delta are not altered. On the basis of these results, BIOLOX. ®. forte can be considered a reliable alternative to other materials in standard applications and the new alumina composite BIOLOX. ®. delta will allow the realization of medical ceramics devices, already in the study phase, such as knee prosthesis, 22-mm ball-heads and thinner wall-thickness of inserts, which could not be developed up to now with the available ceramic materials

Sufficient vascularization is essential for osseointegration of biomaterials and their substitution by new bone. Angiogenic growth factors such as VEGF are promising agents to promote the vascularization of bone substitutes. To optimize the efficacy of VEGF delivery a continuous administration of low concentrations of VEGF seems to be beneficial. We hypothesized that a long-term release of VEGF from calcium phosphate ceramics may induce a sustained angiogenic response and sufficiently promote biomaterial vascularization in vivo. Vascular endothelial growth factor (VEGF, Genentech Inc., South San Francisco, USA.) was co-precipitated onto biphasic calcium phosphate ceramics (BCP, 80% HA, 20% β-TCP) at a concentration of 1μg/ml and 5μg/ml. The passive release and the cell-mediated release of VEGF were analyzed over 19 days by ELISA. For in vivo investigations BCP ceramics were implanted into a cranial window preparation in Balb/c mice. Angiogenesis and vascularization were investigated over 28 days by means of intravital microscopy. Functional capillary density (FCD, mm/mm. 2. ) served as parameter of biomaterial vascularization. Co-precipitation of VEGF onto BCP ceramics resulted in a significant improvement of protein retention as compared to conventional adsorption of the growth factor [Cumulative VEGF release: Adsorption: 320 ± 2.6 ng/ml, Co-precipitation 116 ± 14.6 ng/ml (p< 0.05)]. Murine bone marrow cells differentiated towards osteoclasts mediated a sustained release of co-precipitated VEGF. Preliminary in vivo results showed a significant increase of functional capillary density after implantation of BCP ceramics co-precipitated with VEGF as compared to negative controls [day 7: 1.7 ± 0.2 mm/mm. 2. vs. 0.9 ± 0.5 mm/mm. 2. ; day 14: 6.1 ± 0.3 mm/mm. 2. vs. 2.1 ± 0.6 mm/mm. 2. ; day 28: 8.7 ± 0.3 mm/mm. 2. vs. 3.9 ± 0.7 mm/mm. 2. , p< 0.05]. At 14 and 28 days after implantation, FCD induced by BCP ceramics co-precipitated with VEGF was significantly higher as compared to FCD induced by ceramics adsorbed with the VEGF [day 14: 6.1 ± 0.3 mm/mm. 2. vs. 4.0 ± 1.4 mm/mm. 2. ; day 28: 8.7 ± 0.3 mm/mm. 2. vs. 5.9 ± 0.7 mm/mm. 2. , p< 0.05]. The release kinetics critically influences the efficacy and the risks of local VEGF administration. By applying a co-precipitation technique the initial high liberation rate of VEGF was reduced and a sustained cell-mediated release at low concentrations was achieved. In vivo, VEGF promoted angiogenesis and vascularization of BCP ceramics. Vessel formation was more pronounced if VEGF was co-precipitated onto ceramics as compared to superficial adsorption of the growth factor, indicating that VEGF delivery at later stages of the healing process is beneficial. The present study provides evidence that, by delivering VEGF in a sustained manner at low local concentrations biomaterial vascularization can be markedly enhanced

Background. Theoretically, improved material properties of new alumina matrix composite (AMC) material, Delta ceramics, are expected to decrease concerns associated with pure alumina ceramics and allow manufacturing thinner liners and consequent larger heads. However, limited short-term clinical results are available and mid-term results of these effects are unclear. Questions/Purposes. (1) Does AMC material decrease the rate of ceramic fracture and noise, concerns of previous-generation ceramics, following change of material properties? (2) Does the possible use of larger heads consequent to manufacturing thinner liners decrease dislocation rate and affect inguinal pain? (3) Do any other complications associated with the use of AMC ceramics occur?. Materials and Methods. One-hundred cementless primary total hip arthroplasties (THAs) using AMC ceramic bearings were performed consecutively by single surgeon. The mean follow-up period was 5.4 years (range, 5.0 to 5.7) and average age at the time of arthroplasty was 54.7 years. Prostheses with identical design and Biolox® Delta ceramics were used in all patients. Clinical evaluation included the occurrence of inguinal pain and noise which was classified into squeaking, clicking, grinding and popping. Ceramic fracture, dislocation and any other complications associated with the use of AMC ceramics were also investigated. Result. No ceramic fracture occurred and noise was reported in three patients (3.2%); three subjective clicking, but no squeaking. Single event of perioperative dislocation due to incompliance occurred in one hip (1.1%) and inguinal pain was reported in two hips (2.1 %); neither evidence of iliopsoas tendinitis on ultrasonography, nor association with ceramic head size (p>0.05). Liner dissociation following initial square seating was shown immediately after surgery in one hip (1.1%) and underwent revision THA. Conclusion. Improved material properties combined with the possible use of larger-diameter head make AMC ceramics a promising alternative bearing option with reduced risk of ceramic fracture, squeaking and dislocation. In spite of these encouraging results, however, meticulous technical precautions such as square seating and proper impaction in particular, should be taken during whole process of liner insertion

In total hip arthroplasty (THA), aseptic loosening induced by polyethylene (PE) wear debris is the most important cause that limits the longevity of implants. Abrasive wear generated through the mechanism such that micrometer-roughened regions and small asperities on the metallic femoral heads surface locally plow through the PE cup surface. Abrasive wear results in the PE material being removed from the track traced by the asperity during the motion of the metallic femoral heads surface. For the purpose of reducing wear, alumina ceramics was introduced in Europe and Japan in 1970s. The clinical results of ceramic-on-PE bearings regarding the wear resistance have been superior to that of the metal-on-PE bearings. Compared with Co–Cr–Mo alloys, alumina ceramics is advantageous for precision machining because of its higher hardness, enable to form spherical and smooth surface. The fracture resistance of the alumina ceramics itself is related to grain size; the grain size reduction leads to the improvement of its resistance. In this study, we evaluated the roundness and the roughness of retrieved two distinct alumina ceramics having different grain size, and Co–Cr–Mo alloy heads. Fourteen retrieved alumina ceramic femoral heads; ten heads with a diameter of 28 mm made of small grain size alumina (SG-alumina; mean grain size is 3.4 μm) with clinical use for 16–28 years and four heads with a diameter of 26 mm made of extra-small grain size alumina (XSG-alumina; mean grain size is 1.3 μm) with clinical use for 14–19 years, were examined. Six retrieved Co–Cr–Mo alloy femoral heads with a diameter of from 22 to 32 mm with average clinical use for 12–28 years were examined. SG-alumina and XSG-alumina heads showed significantly lower roundness compared with Co–Cr–Mo alloy heads, due to higher precision machining [Fig. 1]. The surface roughness for the contact area of the heads increased in order of XSG-alumina, SG-alumina and Co–Cr–Mo alloy. The surface roughness of the non-contact area for all kinds of heads was lower than that for the contact area [Fig. 2]. Surface profiles of the SG-alumina and XSG-alumina showed the reentrant surface while Co–Cr–Mo alloy heads showed the protrusion surface. The roundness and roughness of the Co–Cr–Mo alloy or ceramic surface and the presence or absence of hard third-body particles correlate to the amount of abrasive PE wear. When the third-body was entrapped during the clinical use, a reentrant surface might be formed on the ceramic while protrusion surface formed on the Co–Cr–Mo alloy. The differences in clinical results may be due in part to the influence of third-body particles. The ceramic becomes more resistant than Co–Cr–Mo alloy against the scratching by the entrapped abrasive contaminants because of its harder surface. From the good clinical results of more than 20 years using SG-alumina, the greater long term clinical results using XSG-alumina will be expected

The reconstruction of bone defects with biomaterials represents a potential alternative to the transplantation of autologous and allogenic bone. Ceramic materials can be combined with growth factors (i.e. BMPs) to render them osteoinductive. Coating of biomaterials with growth factors has mostly been attempted by adsorption onto the material’s surface. The superficial deposition usually results in an immediate passive release of the proteins, thus restricting their temporal availability during bone healing. It was hypothesized that a co-precipitation of proteins onto calcium phosphate ceramics may provide the possibility to achieve a prolonged release of proteins from the material without impairing the biologic activity of growth factors. Tritium labelled bovine serum albumin ([3H]BSA) and recombinant human BMP2 (rhBMP2) were coated onto biphasic calcium phosphate (BCP) ceramics using a coprecipitation technique of proteins together with calcium phosphate (Liu Y et al. 2001). The co-precipitation was compared to conventional adsorption of proteins to ceramic materials. The passive and cell-mediated release of [3H]BSA was investigated during 19 days. To analyze the cell-mediated protein release, murine bone marrow cells were seeded onto ceramics and differentiated to osteoclasts or to monocytes/macrophages. To assess whether rhBMP2 co-precipitated to BCP ceramics retained its biologic activity the growth factor’s ability to induce the differentiation of primary murine osteoblasts was studied. After 19 days 71.7±5.3% of the adsorbed [3H]BSA was passively released (63.0±6.0% within 4 days). The passive liberation of [3H]BSA was effectively reduced using the coprecipitation technique (12.5±2.0% within 19 days, 10.1±2.3% within 4 days, p< 0.001). Further analysis demonstrated a sustained, osteoclast-mediated release of coprecipitated [3H]BSA from calcium phosphate ceramics which was blocked by the addition of calcitonin. Passive release of adsorbed and co-precipitated BMP2 led to a temporally restricted stimulation of murine osteoblasts. Cell-mediated liberation of co-precipitated BMP2 induced a sustained stimulation of the differentiation of osteoblasts. The successful application of exogenously added growth factors depends critically on the mode of delivery. It has been shown that a sustained availability of BMP2 is beneficial for bone healing. Application of the co-precipitation technique resulted in a long-term release of proteins from BCP ceramics mediated by active resorbing osteoclasts without impairing the biologic activity of rhBMP2. Co-precipitating growth factors onto BCP ceramics provides a potential to shift the initial extensive liberation to a sustained release of bioactive proteins. This method of protein delivery may represent a possibility to achieve a more physiological availability of growth factors during bone regeneration

Oxide ceramics, such as alumina and zirconia have been used extensively in arthroplasty bearings to address bearing wear and mitigate its delayed, undesirable consequences. In contrast to oxide ceramics that are well-known to orthopaedic surgeons, silicon nitride (Si. 3. N. 4. ) is a non-oxide ceramic that has been investigated extensively in very demanding industrial applications, such as precision bearings, cutting tools, turbo-machinery, and electronics. For the past four years, Si. 3. N. 4. has also been used as a biomaterial in the human body; specifically in spinal fusion surgery. As a implantable biomaterial, Si. 3. N. 4. has unique properties, such as high strength and fracture toughness, inherent chemical and phase stability, low wear, proven biocompatibility, excellent radiographic imaging, antibacterial advantages, and superior osteointegration. This property combination has proven beneficial and desirable in orthopaedic implants made for spinal fusion, spinal disc reconstruction, hip and knee arthroplasty, and other total joints (Fig. 1). The physical properties, shapes, sizes and surface features of Si. 3. N. 4. can be engineered for each application – ranging from dense, finely polished articulation components, to highly porous scaffolds that promote osteointegration. Both porous and polished surfaces can be incorporated in the same implant, opening a number of opportunities for arthroplasty implant design. Crack propagation modes for in situ toughened Si. 3. N. 4. differ favorably from those of conventional ceramics, rendering Si. 3. N. 4. extremely resistant to catastrophic failure in vivo (Fig. 2). Most significantly, our recent work has shown that Si. 3. N. 4. is resistant to bacterial biofilm formation, colonization and growth, when compared to medical-grade PEEK and titanium. These anti-infective characteristics are particularly valuable for in vivo implantation. We will present the unique properties and characteristics of Si. 3. N. 4. , and compare these to other ceramic and non-ceramic biomaterials. Si. 3. N. 4. was once used only in industrial applications, but early data show that this novel biomaterial is positively impacting orthopaedic care and will continue to do so into the future

Currently available calcium silicate based ceramics pseudowollostonite (CaSiO3) ceramics are regarded as a potential bioactive material for bone tissue regeneration due to their osseointegration properties. A drawback of CaSiO3 ceramics is that they possess high dissolution rate, leading to a high pH value in the surrounding environment thereby affecting the biological activity of bone cells. We hypothesize that chemical modification of CaSiO3 ceramics will improve their physical and biological properties. The coordinated activities of osteoblasts (OB) and osteoclasts (OC) are critical for proper bone remodelling. Moreover, growing evidence indicate that vascular endothelial cells are involved in bone development and remodelling. Present study aims at Chemically modifying CaSiO3 by incorporating zinc (Zn) and titanium (Ti) into their structure to develop novel materials Hardystonite (HT, Ca2ZnSi2O7) and Sphene (CaTiSiO5), respectively and to determine their effect on bone cells OB & OC and on endothelial cells. It is well known that cell behaviour in a culture system is influenced by the physiochemical characteristics of the substrate. Human bone derived cells (HBDC) cultured on HT and Sphene supported the HBDC attachment (cells exhibited well defined cytoskeletal structure) showed characteristic features of cellular proliferation and differentiation. In addition, Zn and Ti incorporation into CaSiO3 supported the formation of mature, active and functional OC. Moreover, the modified bio-materials were found to be conducive to Human micro-vascular dermal endothelial cell growth. Our results suggest that HT and Sphene possessed an improved physical characteristics and enhanced biological activities of bone cells (OB & OC) and endothelial cells thus rendering it a potential material for bone tissue regeneration and coatings onto commonly used orthopaedic and dental implants

Although alumina has been used in orthopaedic surgery since the 1970s, the long-term clinical results of zirconia have not been well documented in vivo. We studied hips with these two different ceramics during the same period and with a minimum follow-up of ten years. Because the size of the alumina and zirconia heads was different, hips with 32 mm alumina heads and those with 28 mm zirconia heads were compared with control hips with stainless-steel heads of the same size. Our aim was to compare the two ceramics. There was an increased linear rate of penetration of the femoral heads into the liner between years five and 12 for the zirconia and the stainless-steel groups. This was severe in the zirconia group (0.4 mm/year compared with 0.13 mm/year for the stainless-steel group). During the same 12-year period there was, however, no significant change in the rate of wear in the alumina group (0.07 mm/year). The mean wear at the most recent follow-up was 1360 mm. 3. for the 28 mm zirconia group, 683 mm. 3. for the 28 mm stainless-steel group, 755 mm. 3. for the 32 mm alumina group and 1314 mm. 3. for the 32 mm stainless-steel group. The monoclinic content rose on the surface of three zirconia heads which were retrieved at revision. This change was associated with an increase in the surface roughness. A change in the roundness with an increase in the sphericity deviation was also observed both in the articular and non-articular parts of the femoral heads. The increase in rate of wear in the zirconia group was only evident after eight years and may be linked to a long-term biodegradation of zirconia in vivo, associated with the altered roughness and roundness which was observed on the retrieved heads

Aims. Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs. Patients and Methods. We investigated tissue collected at revision surgery from nine ceramic-on-ceramic articulations. we compared our findings with tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes. The latter were analyzed to assess the amount of tissue fibrosis that might have been present at the time of implantation to enable evaluation, in relation to implantation time, of any subsequent response in the tissues. Results. There was a significant increase in tissue fibrosis with implantation time for all implant types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was significantly increased compared with metal-on-metal and ceramic-on-polyethylene. Additionally, we found ceramic wear particles in the periprosthetic tissue of ceramic implants. Fibroblasts responded with expression of cytokines when cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA) ceramic surfaces. This response was more pronounced on ATZ ceramics compared with ZTA ceramics. The same inflammatory response was observed with peripheral blood mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion. Our findings therefore, corroborate the previous findings that ceramic-on-ceramic periprosthetic revision tissue is fibrous and offer an explanation for this observation. We detected a long-term inflammatory response of PBMCs and an inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings partially explain the fibrotic tissue change in periprosthetic tissue of ceramic-on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882–90

In biomaterial engineering the surface of an implant can influence cell differentiation, adhesion and affinity towards the implant. Increased bone marrow derived mesenchymal stromal cell (BMSC) differentiation towards bone forming osteoblasts, on contact with an implant, can improve osteointegration. The process of micropatterning has been shown to improve osteointegration in polymers, but there are few reports surrounding ceramics. The purpose of this study was to establish a co-culture of BMSCs with osteoclast progenitor cells and to observe the response to micropatterned zirconia toughened alumina (ZTA) ceramics with 30 µm diameter pits. The aim was to establish if the pits were specifically bioactive towards osteogenesis or were generally bioactive and would also stimulate osteoclastogenesis that could potentially lead to osteolysis. We demonstrate specific bioactivity of micropits towards osteogenesis with more nodule formation and less osteoclastogenesis. This may have a role when designing ceramic orthopaedic implants

Summary Statement. Repetitive concavities threaded on the surface of bone implants have been already demonstrated to be effective on ectopic bone formation in vivo. The aim of this study was to investigate the effect of concavity on the mineralization process in vitro. Introduction. The role of implant surface geometry in bone formation has been extensively investigated. Ripamonti and co. investigated the possibility to induce bone formation by threading concavities on the surface of calcium phosphate implants, without the need for exogenous osteogenic soluble factors. The underlying hypothesis was that this geometry, by resembling the hemi-osteon trench observable during osteoclastogenesis, was able to activate the ripple-like cascade of bone tissue induction and morphogenesis. Despite several studies indicating a positive effect of concavities on bone induction, so far no attempts have rationalised this phenomenon by means of in vitro tests. Consequently, this study aimed to evaluate the effect of surface concavities on the mineralization of hydroxyapatite (HA) and beta-tricalciumphosphate (b-TCP) ceramics in vitro. Our hypothesis was that concavities could effectively guide the mineralization process in vitro. Materials and Methods. Different-size concavities were threaded into the surface of HA and b-TCP semi-sintered disks: 1.8 (large concavity, LC), 0.8 (medium concavity, MC) and 0.4 mm (small concavity, SC). Disks were fully sintered at 1200 or 1100 °C and soaked in simulated body fluid (SBF) up to 28 days. Distinct experiments were carried out in order to assess the role of chemical composition, sintering temperature and concavity size on the extent of mineralization in vitro. The mineralization process was followed by SEM, EDS, XRD and Ca assay tests. Results and Discussion. Massive mineralization occurred exclusively at the surface of the HA disks treated at 1200 °C. Firstly, aggregates of spherical-like amorphous calcium phosphate nucleated specifically within concavities and not on the planar surface. At a later stage, a flake-like apatitic phase replaced the spherical-like apatite and spread out the concavities until covering the entire disk surface. Instead, a lower extent of mineralization occurred on HA disk treated at 1100 °C, with no formation of flake-like phase. In contrast, no significative mineralization was observed for b-TCP disks, irrespective of sintering temperature. Finally, the extent of mineralization on disks exhibiting SC on the surface was found to be about 120- and 10-fold higher than mineralization disks threaded with LC and MC, respectively. Conclusions. The main results of this study are: i) the in vitro mineralization process of CaP ceramics with surface concavities starts preferentially within the concavities and not on the planar surface; ii) concavity size is an extremely effective parameter for controlling the extent of mineralization in vitro. Finally, the results reported in this study suggest correlation between the positive effect of concavities on mineralization in vitro and on ectopic bone formation in vivo

Ceramic-on-ceramic was shown to have advantageous tribologic properties (low wear and friction). For medical applications two ceramics, alumina and zircona, are available. This case study shows that the combination of different ceramics for hard-hard pairings can be critical. A 57 year old patient received a total hip prosthesis (cementless stem with a ceramic head and a monolithic ceramic cup). Thirty-five months postoperatively the patient complained about squeaking noises during walking and stair climbing. Clinical diagnoses showed a good range of motion and no signs of loosening. Conventional rehabilitation did not improve the situation and 43 months after primary surgery the cup and the head had to be revised on the patients request. Intraoperatively no loosening indications were found. The explanted components were analysed using a 3D co-ordinate measuring machine. The head and the cup were made of different ceramics. The zirconia (ZrO2) head occurred rather white whereas the alumina (Al2O3) cup was yellow-reddish. The inner articulating surface of the cup showed no decoloration or wear. The surface of the head contained mated areas with surface defects in equatorial regions (maximum wear depth 9μm). The head and the cup were combined from different manufacturers. The distinct surface changes and wear marks of the zirconia head probably caused the squeaking noise after 3 years in situ. Zirconia for medical applications is generally Y-TZP ceramic. Pressure, heating, and water can cause severe surface embrittlement. Pre-damaging due to the manufacturing process or friction in the joint might be the mechanism leading to pre-mature wear and failure. Joint components from different manufacturers should only be implanted with proper official authorisation

Purpose of the study: Biphasic macroporous phosphocalcium ceramics are used in routine surgery to fill bone defects. This type of material presents the characteristics of an ideal substitute: free of the adverse effects of grafts, biocompatibility, bioactivity, osteoconduction, osteointegration, reproducibility, availability in sufficient quantity. The purpose of our work was to evaluate the role of osteointegration on the resistance of two macroporous biphasic phosphocalcium ceramics routinely proposed on the French market. These two macroprous materials have a similar chemical composition but vary by the presence or not of interpores. Material and methods: The experimental model involved the implantation of ceramic cylinders in a femoral cortical site in sheep, via the intermediary of conduction chambers with specific cortical entrances. The resistance to compression of the implanted samples an non implanted controls was measured using the same ISO norms. Results: After two months implantation in a cortical site in the sheep, Eurocer200plus. ®. exhibited a significant 38% increase in resistance to compression while in the same conditions, Triosite. ®. exhibited a 41% decline in resistance. For ceramics with open porosity, the interpores acted like tunnels enabling rapid colonization for osteoforming cells and early formation of new bone reaching the centre of the substitute, and leading to increased material resistance. Cell colonization of a ceramic with closed porosity is, on the contrary, slowed by the partitions, while its dissolution by biological fluids within the micropores occurs in all materials; there results an imbalance between absorption and synthesis, leading to loss of mechanical resistance as a first phase of osteointegration. Discussion: Open macroposity enables an improvement in the mechanical properties of a biphasic ceramic substitute due to more rapid osteointegration. In the future, material associated with osteoinduction cells or proteins should play an important role, together with changes in the architecture of the ceramic skeleton which should play a determining role in terms of physical and biological properties

INTRODUCTION. Wear, aseptic loosening, dislocation, corrosion and prosthetic joint infection (PJI) are major factors leading to revision of THA. The effect of using ceramic components to address these issues was investigated to determine their behaviour and potential benefit. METHODS. a) Wear determination in off-normal conditions. A series of CoC articulations (32mm) was evaluated using a hip simulator (ISO 14242) up to 4 million cycles in presence of fine alumina particles (48mg/ml). Wear was measured gravimetrically. b) Friction moment determination. Friction moments were measured in a hip simulator with 25% newborn calf serum as lubricant. CoC, CoPE, MoPE, MoXLPE and CoXLPE with articulating diameters ranging between 28 and 40mm were used. The cup was inclined to a constant angle of 33° and rotated ±20° sinusoidally around a horizontal axis at 1Hz. Peak friction moments were measured around the cup rotation axis during a constant joint force period of 1700N between 200 and 210 seconds. c) Infections. Four databases were analysed and additionally data from registers and literature were reviewed to determine the risk of revision for prosthetic joint infection (PJI) dependence on the bearing. Only data for cementless THA were used. Several studies also included analysis of several confounding factors like age at surgery, BMI, pathology, etc. using Cox multivariate analysis. RESULTS. a) Wear determination in off-normal conditions. Loading the test medium with alumina particles didn't produces detectable wear. Opaque areas appeared only after 3 million load cycles, but the wear-rate remained within the gravimetric measurement detection limit (about 0.1–0.2mg) indicating the still extremely low wear-rate of the tested couplings. b) Friction moment determination. The highest moments were measured for metal heads; the lowest for CoC bearings. 40mm CoC bearing showed a similar friction moment like 28mm bearings when coupled with a XLPE liner. c) Infections. The rate of revisions for PJI for 500'749 patients from various studies was in the range of 0.2 to 1.1%. Age at surgery and BMI did not influence septic loosening, while the bearing did; sometimes significant. The trend was identical for all seven sources and ceramic components resulted in a lower incidence of revisions for up to 60%. CONCLUSION. The wear of CoC articulations is extremely low even in a heavily contaminated environment with fine hard particles. Such high scratch resistance makes CoC the preferable revision solution in THA. Friction moments with CoC are the lowest, even with large diameter bearings. The low friction moments of ceramics lower the stresses at the modular and also bone interface and can affect the outcome of THA. Revisions due to infection seem to be also dependent on the bearing couple with a positive influence of ceramic components. Although due to the complex reasons for infections only a trend, CoP and CoC has been identified to mitigate the risk of PJI

Introduction. Silicon nitride (Si3N4) is a ceramic material presently implanted during spine surgery. It has a fortunate combination of material properties such as high strength and fracture toughness, inherent phase stability, scratch resistance, low wear, biocompatibility, hydrophilic behavior, easier radiographic imaging and resistance to bacterial biofilm formation, all of which make it an attractive choice for orthopaedic applications beyond spine surgery. Unlike oxide ceramics, (e.g., alumina or Al2O3) the surface chemistry and topography of Si3N4 can be precisely engineered to address in vivo demands. Si3N4 can be manufactured to have an ultra-smooth, or highly fibrous, or porous morphology. Its chemistry can be varied from that of a silica-like surface composed of silanol moieties to one which is predominately comprised of silicon-amine functional groups. Methods. In the present study, a Si3N4 bioceramic formulation was exposed to thermal, chemical, and mechanical treatments in order to induce changes in surface composition and features. The treatments included grinding and polishing, etching in hydrofluoric acid solution, and heating in nitrogen or air. Resulting surfaces were characterized using a variety of microscopy techniques to assess morphology. Surface chemical and phase composition were determined using x-ray photoelectron and Raman spectroscopy, respectively. Streaming potential measurements evaluated surface charging, and sessile water drop techniques assessed wetting behavior. Results. Induced changes to surface morphology and wetting behavior are shown in Figure 1. A wide variety of wetting behavior was observed, ranging from moderate hydrophilicity (θ ∼60°) in the case of untreated surfaces to extreme hydrophilicity (θ <10°) in the case of surfaces subjected to heat treatments in different atmospheres. Figure 2 shows the zeta potential as a function of solution pH for the surfaces shown in Figure 1. All samples exhibit strong negative surface charging at homeostatic pH (−40 mV or more), and the oxidized sample exhibits extremely strong charging (−75 mV). Conclusions. Our data show that Si3N4 is a facile biomaterial whose material properties can be engineered and optimized for specific applications. This work provides a basis for future in vitro and in vivo studies which will examine the effects of these treatments on important orthopaedic properties such as friction, wear, protein adsorption, bacteriostasis and osseointegration