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)

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

Introduction

The incidences of fragility fractures, often because of osteoporosis, are increasing. Research has moved towards bioresorbable scaffolds that provide temporary mechanical stability and promote osteogenesis. This research aims to fabricate a 3D printed composite Poly (l-lactic-co-glycolic acid)-strontium doped tricalcium phosphate (PLGA-SrTCP) scaffold and evaluate in an in vitro co culture study containing osteoporotic donor cells.

Objectives

There is increasing application of bone morphogenetic proteins (BMPs) owing to their role in promoting fracture healing and bone fusion. However, an optimal delivery system has yet to be identified. The aims of this study were to synthesise bioactive BMP-2, combine it with a novel α-tricalcium phosphate/poly(D,L-lactide-co-glycolide) (α-TCP/PLGA) nanocomposite and study its release from the composite.

Background context

Fusion is a fundamental procedure in spine surgery. Although autogenous grafts have ideal bone graft characteristics, their use may remain limited due to various morbidities. Even though ceramic based synthetic bone grafts are used commonly at present, in order to enhance their efficacy, their combined use with other materials has been investigated. The use of carbon nanotubes (CNTs) together with synthetic bone grafts such as hydroxyapatite (HA) has contributed to positive developments in bone tissue engineering.

Aternatives to autogenous bone graft for spinal fusion have been investigated for many years. It has been shown that osteoconductive materials alone do not give a rate of fusion which is comparable to that of autogenous bone graft. We analysed the effectiveness of porous ceramic loaded with cultured mesenchymal stem cells as a new graft material for spinal fusion in an animal model.

Posterolateral fusion was carried out at the L4/L5 level in 40 White New Zealand rabbits using one of the following graft materials: porous ceramic granules plus cultured mesenchymal stem cells (group I); ceramic granules plus fresh autogenous bone marrow (group II); ceramic granules alone (group III); and autogenous bone graft (group IV). The animals were killed eight weeks after surgery and the spines were evaluated radiographically, by a manual palpation test and by histological analysis.

The rate of fusion was significantly higher in group I compared with group III and higher, but not significantly, in group I compared with groups II and IV. In group I histological analysis showed newly formed bone in contact with the implanted granules and highly cellular bone marrow between the newly formed trabecular bone. In group II, thin trabeculae of newly formed bone were present in the peripheral portion of the fusion mass. In group III, there was a reduced mount of newly formed bone and abundant fibrous tissue. In group IV, there were thin trabeculae of newly formed bone close to the decorticated transverse processes and dead trabecular bone in the central portion of the fusion mass.

In vitro cultured mesenchymal stem cells may be loaded into porous ceramic to make a graft material for spinal fusion which appears to be more effective than porous ceramic alone. Further studies are needed to investigate the medium- to long-term results of this procedure, its feasibility in the clinical setting and the most appropriate carrier for mesenchymal stem cells.

Critical-sized bone defects remain challenging in the clinical setting. Autologous bone grafting remains preferred by clinicians. However, the use of autologous tissue is associated with donor-site morbidity and limited accessibility to the graft tissue. Advances in the development of synthetic bone substitutes focus on improving their osteoinductive properties. Whereas osteoinductivity has been demonstrated with ceramics, it is still a challenge in case of polymeric composites. One of the approaches to improve the regenerative properties of biomaterials, without changing their synthetic character, is the addition of inorganic ions with known osteogenic and angiogenic properties. We have previously reported that the use of a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50% beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating of the TCP particles can enhance the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) (3). To further support the regenerative properties of these scaffolds, inorganic ions with known angiogenic properties, copper or cobalt, were added to the coating solution. β-TCP particles were immersed in a zinc and copper or zinc and cobalt solution with a concentration of 15 or 45 mM. 3D porous scaffolds composed of 1000PEOT70PBT30 and pure or coated β-TCP were additively manufactured by 3D fibre deposition. The osteogenic and angiogenic properties of the fabricated scaffolds were tested in vitro through culture with hMSCs and human umbilical vein endothelial cells, respectively. The materials were further evaluated through ectopic implantation in an in vivo mini-pig model. The early expression of relevant osteogenic gene markers (collagen-1, osteocalcin) of hMSCs was upregulated in the presence of lower concentration of inorganic ions. Further analysis will focus on the evaluation of ectopic bone formation and vascularisation of these scaffolds after implantation in a mini-pig ectopic intramuscular model

The implantation of endoprosthesis is a routine procedure in orthopaedics. Endoprosthesis are mainly manufactured from ceramics, polymers, metals or metal alloys. To ensure longevity of the implants they should be as biocompatible as possible and ideally have antibacterial properties, to avoid periprosthetic joint infections (PJI). Various antibacterial implant materials have been proposed, but have so far only been used sporadically in patients. PJI is one of the main risk factors for revision surgeries. The aim of the study was to identify novel implant coatings that both exhibit antibacterial properties whilst having optimal biocompatibility. Six different novel implant coatings and surface modifications (EBM TiAl6V4, strontium, TiCuN, TiNbN, gentamicin phosphate (GP), gentamicin phosphate+cationic polymer (GP+CP)) were compared to standard CoCrMo-alloy. The coatings were further characterized with regard to the surface roughness. E. coli and S. capitis were cultured on the modified surfaces to investigate the antibacterial properties. To quantify bacterial proliferation the optical density (OD) was measured and viability was determined using colony forming units (CFU). Murine bone marrow derived macrophages (BMMs) were cultured on the surfaces and differentiated into osteoblasts to quantify the mineralisation using the alizarin red assay. All novel coatings showed reduced bacterial proliferation and viability compared to standard CoCrMo-alloy. A significant reduction was observed for GP and GP+CP coated samples compared to CoCrMo (OD. GP,E.coli. = 0.18±0.4; OD. GP+CP,E.coli. = 0.13±0.3; p≤0.0002; N≥7-8). An increase in osteoblast-mediated mineralisation was observed on all surfaces tested compared to CoCrMo. Furthermore, GP and GP+CP coated samples showed a statistically significant increase (M. GP. = 0.21±0.1; M. GP+CP. = 0.25±0.2; p<0.0001; N≥3-6). The preliminary data indicates that the gentamicin containing surfaces have the most effective antibacterial property and the highest osseointegrative capacity. The use of antibiotic coatings on prostheses could reduce the risk of PJI while being applied on osseointegrative implant surfaces

The need for an artificial scaffold in very large bone defects is clear, not only to limit the risk of graft harvesting, but also to improve clinical success. The use of custom osteoconductive scaffolds made from biodegradable polyester and ceramics can be a valuable patient friendly option, especially in case of a concomitant infection. Multiple types of scaffolds for the Masquelet procedure (MP) are available, however these frequently demonstrate central graft involution when defects exceed a certain size and the complication rates remains high. This paper describes three infected tibial defect nonunions with a segmental defect over ten centimeters long treated with a customized 3D printed polycaprolactone-tricalcium phosphate (PCL-TCP) cage in combination with biological adjuncts. Three male patients, between the age of 37 and 47, were treated for an infected tibial defect nonunion after sustaining Gustilo grade 3 open fractures. All had a segmental midshaft bone defect of more than ten centimeters (range 11–15cm). First stage MPs consisted of extensive debridement, external fixation and placement of anterior lateral thigh flaps (ALT). Positive cultures were obtained from all patients during this first stage, that were treated with specific systemic antibiotics during 12 weeks. The second stage MP was carried out at least two months after the first stage. CT scans were obtained after the first stage to manufacture defect-specific cages. In the final procedure a custom 3D printed PCL-TCP cage (Osteopore, Singapore) was placed in the defect in combination with biological adjuncts (BMAC, RIA derived autograft, iFactor and BioActive Glass). Bridging of the defect, assessed at six months by CT, was achieved in all cases. SPECT-scans 6 months post-operatively demonstrated active bone regeneration, also involving the central part of the scaffold. All three patients regained function and reported less pain with full weight-bearing. This case report shows that 3D printed PCL-TCP cages in combination with biological adjuncts is a novel addition to the surgical treatment of very large bone defects in (infected) posttraumatic nonunion of the tibia. This combination could overcome some of the current drawbacks in this challenging indication

Background. As the number of ceramic THR bearings used worldwide is increasing, the number of implants that experience off-normal working conditions, e.g. edge loading, third bodies in the joint, soft tissues laxity, dislocation/subluxation of the joint, increases too. Under all such conditions the bearing surfaces can be damaged, leading eventually to a limitation of the expected performances of the implant. Methods. We characterised the damage resistance of different bearing surfaces (alumina matrix composite BIOLOXdelta, alpha-alumina BIOLOXforte, zirconia 3Y-TZP, oxidized zirconium alloy Zr-2.5Nb, CoCr-alloy) by scratch tests performed following the European standard EN 1071–3:2005. Also the scratch hardness of same materials has been assessed. Results. The Lc1 value (i.e., the load for the onset of a scratch) measured for BIOLOXdelta is about fivefold the one measured for the oxidized zirconium alloy (OXZr) surface and about tenfold the Lc1 measured for the CoCr alloy. The height of ridges along the scratch edges due to plastic flow in the composite ceramic BIOLOXdelta are only 21% in height than in CoCr, and only a small fraction (0.04%) of the height of ridges measured on OXZr surfaces. The scratch hardness of the metal samples tested (CoCr, OXZr) results one order of magnitude lower than the ones of ceramics. This behavior is not influenced by of the presence of the coating on OXZr surface. Conclusions. The transformation toughened ceramics tested (BIOLOXdelta, 3Y-TZP) are the materials that exhibit the higher resistance to scratching. Ridges at scratch edges are lower in ceramics than in coated or uncoated metals. The result show the superior scratch resistance behavior of toughened ceramics for THR wear couples with respect to coated or bare alloys. Level of Evidence. Level 1

Abstract. Objectives. Current use of hard biomaterials such as cobalt-chrome alloys or ceramics to articulate against the relatively soft, compliant native cartilage surface reduces the joint contact area by up to two thirds. This gives rise to high and abnormal loading conditions which promotes degradation and erosion of the mating cartilage leading to pain, stiffness, and loss of function. Biomimetic soft lubrication strategies have been developed by grafting hydrophilic polymers onto substrates to form a gel-type surface. Surface grafted gels mimic the natural mechanisms of friction dissipation in synovial joints, showing a promising potential for use in hemiarthroplasty. This project aims to develop implant surfaces with properties tailored to match articular cartilage to retain and promote natural joint function ahead of total joint replacement. Methods. Four different types of monomers were grafted in a one-step photopolymerisation procedure onto polished PEEK substrates. The functionalised surfaces were investigated using surface wettability, FTIR, and simplified 2D-tribometry tests against glass and animal cartilage specimens to assess their lubricity and mechanical properties for hemiarthroplasty articulations. Results. Polymer functionalised surfaces under different grafting conditions were assessed for their wettability, graft density and quality. A reduction in water contact angle from 90° to < 20° was seen for functionalised highly hydrophilic PEEK surfaces. Similarly a reduction in the coefficient of friction (and subsequently shear stresses acting on cartilage) of 95% to ∼ 10. −2. was seen for functionalised PEEK surfaces slid against glass and cartilage in PBS. Conclusions. Development of this technology has the potential to vastly improve the performance of hemiarthroplasty. Providing earlier and targeted interventions for degenerative joint disease whilst preserving the function of the remaining healthy cartilage. Future work will concern using these promising hydrated functionalised surface architectures as focal cartilage deflects plugs along with long-term performance and suitability for implantation assessments using joint simulator testing

Introduction and Objective. Despite pure alumina have shown excellent long-term results in patients undergoing total hip arthroplasty (THA), alumina matrix composites (AMCs) composed of alumina and zirconium oxide are more commonly used. There are no comparative studies between these two different ceramics. We performed a retrospective case-control study to compare results and associated complications between AMC from two manufacturers and those with pure alumina from another manufacturer. Materials and Methods. 480 uncemented THAs with ceramic on ceramic (CoC) bearing surfaces (288 men and 192 women; mean age of 54.1 ± 12.4 years), were implanted from 2010 to 2015. Group 1: 281 THAs with pure alumina; Group 2A: 142 with AMC bearing in a trabecular titanium cup. Group 2B: 57 hips with AMC bearing with a porous-coated cup. Results. The mean follow-up was 7.3 years. There was one late infection in group 1, eight dislocations, three in group 1 (1.1%), three in group 2A (2.1%), all with a 36 mm femoral head, and two in group 2C (3.5%). Liner malseating was found in one hip in group 1, and in five hips in group 2C, of these, there were four liner fractures (7.0%). Four cups were revised for iliopsoas impingement (three in group 1 and one in group 2B). Two cups were revised for aseptic loosening, one in group 1 and one in group 2A, and four revised femoral stems in group 2A, three for subsidence and another for postoperative periprosthetic B. 2. fracture. The mean preoperative Harris Hip Score was 48.6 ± 3.3 in the whole series and 93.9 ± 7.2 at the end of follow-up. The survival rate of revision for any cause was 98.2% (95% Confidence Interval: 96.6–99.8) at ten years for group 1, 95.8% (95% CI: 92.1–99.5) for group 2A, and 91.1% (95% CI: 83.7–98.5) for group 2B (log-rank 0.030). Conclusions. Outcome of uncemented CoC THA in young patients was satisfactory at mid-term in all three groups. However, liner fractures were frequent in group 2B. All dislocated hips in group 2A had a 36 mm femoral head diameter, and revision due to any cause was less frequent in group 1. Pure alumina CoC THA can be used as a benchmark for comparison with newer CoC THAs

To date there has been no material for endoprosthetics providing excellent resistance to abrasion and corrosion combined with great tensile strength, fracture toughness, and bending strength, as well as adequate biocompatibility. Carbon-fiber-reinforced silicon carbide (C/SiC, C/C-SiC or C/SiSiC) is as a ceramic compound a potentially novel biomaterial offering higher ductility and durability than comparable oxide ceramics. Aim of this investigation was to test the suitability of C/SiC ceramics as a new material for bearing couples in endoprosthetics. One essential quality that any new material must possess is biocompatibility. For this project the in-vitro biocompatibility was investigated by using cuboid like scaffolds made of CMC. To determine whether the material is suited as a lubricant partner in endoprosthetics, we measured its abrasion coefficient and wear tolerance against various antibodies. The C/SiC samples tested were produced via the Liquid Silicon Infiltration (LSI) of pyrolized porous fiber preforms made by warm-flow pressing free-flowing granulates on a hydraulic downstroking press with a heated die of the type HPS-S, 1000 kN. After preparation of the composites, the tribological characteristics are determined. Flexural strength was determined at room temperature according to DIN685-3 with an universal testing machine Z100 and the Young”s -modulus was carried out via resonant frequency-damping analysis RFDA. The samples”surface as well as cell adhesion and cell morphology were assessed via ESEM. The human osteoblast-like cell line MG-63 and human ostoeblast were used for cel culture ecperiments (WST, Live/dead, Cytotoxicity, cell morphology). Based on the raw data the mean value and the standard deviation were calculated. The Mann-Whitney-U-Test was used to evaluate the differences between experiment and control samples. The flexural strength at room temperature is approx. 180 MPa, while the elongation at break is about 0.13%. The Young”s modulus is detected between 120 and 150 GPa. The density lies between 2.5 and 3.0 g/cm. 3. We noted a friction coefficient µ between 0.31. The cell lines exhibited no morphological alterations, and adhered well to the C/SiC samples. Vitality was not impaired by contact with the ceramic composite. Cell growth was observed evenly distributed over a 21-day period. In the future, investigators aiming to apply this composite in endoprosthetics will have to focus on its efficacy in conjunction with sudden, strong demands, and long-term performance in bodily fluids within joint simulators, etc. In conclusion: C/SiC can definitely be considered a new material with genuine potential for use in endoprosthetics

Background. With promising antibiofilm properties, rifampicin is considered as a cornerstone in the complementary treatment of bone and joint infections. But, achieving an adequate concentration of rifampicin long-term in bone tissue is a challenge. Long-term systemic administration also comes with concomitant side effects. Thus, local delivery of rifampicin in a carrier to ensure the high local concentration of antibiotic in surgical site after intervention due to infection could be a valuable alternative. However, an ideal platform for local delivery of rifampicin is still lacking. A calcium sulphate/hydroxyapatite (CaS/HA) (Cerament, Bonesupport AB, Sweden) biomaterial was used as a local delivery platform. Here we aimed 1) to evaluate the injectability of CaS/HA hand-mixed with rifampicin at various concentrations up to maximum one daily dose used systemically in clinical practice 2) to test a clinically used and commercially available mixing device containing the biphasic ceramic with rifampicin. Materials & Methods. Three different concentrations (100 mg, 300 mg and 600 mg) of rifampicin powder (Rifampicin Ebb, Sanofi S.P.A, Italy) diluted in 5 mL of mixing solution (C-TRU, Bonesupport AB, Sweden) were used. Rifampicin solution was mixed to the CaS/HA powder and the injectability of the CaS/HA plus rifampicin composite was evaluated by extruding 250 µL of paste manually through a graduated 1 mL syringe connected to an 18G needle (Ø=1.2 mm, L=4 cm). Mixing was done with a spatula for 30 s at 22°C ±1°C. Total weight of the paste before and after extrusion were measured. To normalize the amount of composite that remained in the needle and syringe tip after injection, the mean of the paste extruded from the syringe at 3 min was calculated for the tested concentrations (normalized value). Injectability (%) was calculated by dividing the weight of the paste extruded from the syringe with normalized value. Each test was repeated for three times at various time points (3, 5, 7 and 9 min). Additionally, 300 mg rifampicin was chosen to mix with the CaS/HA in a commercially available mixing system, which is used clinically. Results. All three combinations of CaS/HA plus rifampicin (100 mg, 300 mg & 600 mg) could be completely extruded from 1 mL syringes at 3 min. At 5 min, 100 mg & 300 mg could still be injected, whereas 600 mg was uninjectable or solidified. At 7 min, rifampicin 100 mg & 300 mg showed 34% and 11% of injectability respectively. At 9 min, no injectability was observed. The material was completely set within 15 minutes with all concentrations. With commercial mixing system, at the recommended injection time of 4 min, 78% of the CaS/HA plus rifampicin (300 mg) composite could be injected. Conclusions. The injectability was reduced with the increasing concentration of rifampicin. CaS/HA plus rifampicin (100 mg and/or 300 mg) could be used by hand mixing and transferred to a syringe or by using an available mixing system containing the ceramic. For higher concentrations of rifampicin, the rheological properties of the ceramics have to be modified for injectability

Different 3D printing techniques for orthopaedic ceramic implants fabrication were compared. Stereolithography of calcium-phosphate slurries makes possible to achieve pre-determined pore size (50 mkm and more) and porosity of 70–80%. For the first time ceramic implants based on double calcium alkali metal phosphates (rhenanites) with given architecture serving good osteoconductivity as well as high resorptivity and strength (up to 10 MPa) were obtained. Development of biomaterials based on calcium phosphates for orthopaedics is an important area of modern materials science. Chemical, physical and mechanical compatibility of this materials is a primary goal for this field. An ideal implant should gradually dissolve and be replaced by the new bone tissue in the patience body. Bone is a multilevel organic/inorganic composite and the main inorganic compound is hydroxyapatite (HA, Ca. 10. (PO. 4. ). 6. (OH). 2. ). Due to this, biomaterials based on HA are widely used, along with biomaterials based on tricalcium phosphate (TCP, Ca. 3. (PO. 4. ). 2. ); however, low solubility of HA (lowest soluble phosphate) as well as TCP does not meet all of the requirements that biomaterials should have. In this work decreasing of the crystal lattice energy approach was used as a strategy of improving the solubility. Modifying the chemical composition by replacing Ca. 2+. cation in the TCP structure by a singly charged alkali metal cation leads to structural changes from TCP to CaMPO. 4. (M=Na, K) – rhenanite. This work focuses on using double calcium alkali metal phosphates Ca. (3 – x). М. 2x. (PO. 4. ). 2. (x = 0–1, М = Na, K) as bioresorbable osteoconductive ceramic implant. Additive manufacturing techniques are the most competitive technology which has been applied in the medical field for the direct or indirect construction of scaffolds and hard or soft tissues. Different techniques were used to prepare ceramics with given structure based on double calcium alkali metals phosphates to improve its osteoconductive properties. High resolution stereolithography (SLA) of ceramic photocurable resins has a great potential in fabrication of high quality complex shaped ceramics. For the first time ceramic implants based on double calcium alkali metal phosphates (rhenanites) with pre-determined pore size (50 mkm and more) and porosity of 70–80% were obtained. Given architecture of scaffold is serving a good osteoconductivity as well as a high resorptivity and strength (up to 10 MPa). High resolution SLA can be easily used for fabrication of a small size implants (3mm in diameter/height or less) for in vivo experiments, and it can be freely used to fit any shade in osteoconductive properties of ceramic materials designed for bone grafting. Russian Science Foundation supported this study under Grant No. 14-19-00752. The authors acknowledge partial support from Lomonosov Moscow State University Program of Development

This study investigates the use of porous biphasic ceramics as graft extenders in impaction grafting of the femur during revision hip surgery. Impaction grafting of the femur was performed in four groups of sheep. Group one received pure allograft, group two 50% allograft and 50% BoneSave, group three 50% allograft and 50% BoneSave type 2 and group four 10% allograft and 90% BoneSave as the graft material. Function was assessed using an index of pre- and post-operative peak vertical ground reaction force ratios. Changes in bone mineral density were measured by dual energy X ray absorptiometry (DEXA) scanning. Loosening and subsidence were assessed radiographically and by histological examination of the explanted specimens. There was no statistically significant difference between the four groups after 18 months of unrestricted functional loading for all outcome measures

Calcium phosphate ceramics and bioactive glasses are frequently used in orthopedic surgery to stimulate the regeneration of bone tissue due to their superior compatibility to bone tissue. Nevertheless, the brittleness and lack of self-healing behavior of bioceramics are still considered as serious drawbacks. Therefore, these bioceramics have been combined with organic biomaterials for several decades. Since the 1990s, the emergence of nanotechnology has accelerated the progress with respect to the development of organic-inorganic nanocomposites of improved functionality compared to conventional composite biomaterials. This presentation focuses on the development of injectable (nano)composites with self-healing and/or load-bearing capacity. To this end, the affinity between polymeric and inorganic components was tuned by modifying non-covalent interactions between both composite components. Specifically, we exploited reversible interactions between hydrogel matrices and inorganic nanoparticles (traditional nanocomposites), hydrogel nanoparticles and inorganic nanoparticles (colloidal nanocomposites), as well as fibers and bioceramic matrices (fiber-reinforced cement composites). The resulting composite biomaterials were mechanically strong and self-healing, which may open up new avenues of research on the applicability of self-healing and load-bearing composite biomaterials for regenerative medicine

Ceramics such as hydroxyapatite are routinely used in fracture repair. However, their effects could be significantly improved as its bioavailability is incredibly poor (issues including low solubility, anionic charge, tendency to agglomerate). Nanoscale hydroxyapatite are gaining much interest, demonstrating increased effectiveness when compared to their micro-sized counterpart. In this study, we have developed a bioactive cargo–polymer-based system that allowed for the sustained, localised non-viral delivery of hydroxyapatite nanoparticles using an amphipathic peptide as a capping agent. The nanoparticles were delivered from a polycaprolactone nanofibre reinforced novel Alg-co-PNIPAAm thermoresponsive hydrogel. The bioactive cargo–polymer-based system was characterised in terms of its physiochemical properties, in vitro properties and in vivo performance using a subcutaneous mouse model. From this study, we have demonstrated that osteogenesis and bone regeneration were significantly increased when our novel capping agent was used to limit the particle size distribution and optimised the physiochemical characteristics of nanoscale hydroxyapatite (i.e. reducing risk of agglomeration and increasing its bioavailability). Additionally, the dual functionality of the thermoresponsive hydrogel as a scaffold for bone regeneration and as a vehicle for the sustained, local delivery of hydroxyapatite nanoparticles over an extended period was successfully demonstrated

20 years ago, we designed injectable bioactive suspensions in water of calcium phosphate ceramics for bone and periapical regenerations. Because of leakage of these suspensions, we focused on injectable hydrogels before to set in situ by chemical crosslinking to form 3D scaffolds. We set up a platform to develop a series of innovative hydrogels for bone, cartilages and periodontal tissue regeneration. We based our strategy on polysaccharides macromolecules because they are renewable materials, that originate from biological sources and generally are biocompatible, non-toxic and biodegradable. We developed a family of silated macromolecules able to react forming biocompatible hydrogels. The silated polymers are self-setting hydrogels able to covalently crosslink under pH variation, without addition of toxic crosslinking agent. All these macromolecules could be combined in multicomponent hydrogels, representing a strategy for improving mechanical properties of biomaterials or to tailor particular properties to meet specific needs. For mineral scaffolding, we realized composites of calcium phosphates particles or cements with hydrogel, increasing the ductility and creating macroporous scaffold to propose foam bone cements well adapted to bone biomaterials and Bone tissue engineering. Perspectives are 3D printing and bio printing techniques. We will use our hydrogels platform to prepare tunable (bio)inks in skeletal medicine

Biphasic calcium phosphates (BCP) are the most frequently used materials because of their mineral analogy with bio-mineral part of bones. Their chemical synthesis can be modulated by doping, in order to respond to the biological needs. We present here the biological responses induced by copper ions in solution, to characterize its cytotoxicity and antibacterial activity. We also investigate the antibacterial property of Cu-doped BCP (Ca10 Cu0.1 (PO4)6 (OH)1.8 O0.2) on a strain of clinical interest: S. aureus, compared to undoped BCP. The sol-gel route has been used to prepare the BCP ceramics. Human BMC (Bone Marrow Cells) were obtained from metaphysal cancellous bone collected during hip arthroplasty and used for cytotoxicity evaluations. A strain of Staphylococcus aureus isolated from an osteoarticular infection after total knee arthroplasty was used to evaluate antibacterial activities. Results indicate that 3 ppm of copper ions leads to the death of all cultured bacteria in 24 hours and 25 ppm caused the death of all cells in 15 days. Regarding BCP, the undoped bioceramics increased the bacterial growth compared to a control without bioceramic. After 16 hours of contact, the copper ions released by the Cu-doped BCP induced a significant decrease of the bacterial concentration, indeed no viable bacteria were found. These materials seem to be a promising alternative for the preparation of multifunctional bone substitutes