Cecilia Persson

The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructions, with both CaP degradation and bone formation. In this study, the volumetric change at the implant site was quantified longitudinally by clinical computed tomography (CT). The retrospective CT datasets had been acquired postoperatively (n=10), in 1-year (n=9) and 3-year (n=5) follow-ups. In the 1-year follow-up, the total volumetric change at the implant site was -8±8%. A volumetric increase (bone formation) was found in the implant-bone interface, and a volumetric decrease was observed in the central region (CaP degradation). In the subjects with 2- or 3-year follow-ups, the rate of volumetric decrease slowed down or plateaued. The reported degradation rate is lower than previous clinical studies on monetite, likely due to the presence of pyrophosphate in the monetite-based CaP-formulation. A 31-months retrieval specimen analysis demonstrated that parts of the CaP had been remodeled into bone. The CaP phase composition remained stable, with 6% transformation into hydroxyapatite. In conclusion, this study demonstrates successful bone-bonding between the CaP-material and the recipient bone, as well as a long-term volumetric balance in cranial defects repaired with the monetite-based composite implant, which motivates further clinical use. The developed methods could be used in future studies for correlating spatiotemporal information regarding bone regeneration and CaP degradation to e.g. patient demographics. STATEMENT OF SIGNIFICANCE: In bone defect reconstructions, the use of calcium phosphate (CaP) bioceramics ideally results in a volumetric balance between bone formation and CaP degradation. Clinical data on the volumetric balance is nevertheless lacking, especially for monetite-based CaPs. Here, this concept is investigated for a composite cranial implant. The implant volumes were quantified from clinical CT-data: postoperatively, one year and three years postoperatively. In total, -8±8% (n=9) volumetric change was observed after one year. But the change plateaued, with only 2% additional decrease at the 3-year follow-up (n=5), indicating a lower CaP degradation rate. Osseointegration was seen at the bone-implant interface, with a 9±7% volumetric change after one year. This study presented the first quantitative spatiotemporal CT analysis of monetite-based CaPs.

INTRODUCTION The fixation of small intraarticular bone fragments is clinically challenging and an obvious first orthopaedic indication for an effective bone adhesive. In the present study the feasibility of bonding freshly harvested human trabecular bone with OsSticR, a novel phosphoserine modified cement, was evaluated using a bone cylinder model pull-out test and compared with a commercial fibrin tissue adhesive. METHODS Femoral heads (n=13) were collected from hip fracture patients undergoing arthroplasty and stored refrigerated overnight in saline medium prior to testing. Cylindrical bone cores with a pre-inserted bone screw, were prepared using a coring tool. Each core was removed and glued back in place with either the bone adhesive (α-tricalcium phosphate, phosphoserine and 20% trisodium citrate solution) or the fibrin glue. All glued bones were stored in bone medium at 37°C. Tensile loading, using a universal testing machine (5 kN load cell), was applied to each core/head. For the bone adhesive, bone cores were tested at 2 (n=13) and 24 (n=11) hours. For the fibrin tissue adhesive control group (n=9), bone cores were tested exclusively at 2 hours. The femoral bone quality was evaluated with micro-CT. RESULTS The ultimate pull-out load for the bone adhesive at 2 hours ranged from 36 to 171 N (mean 94 N, SD 42 N). At 24 hours the pull-out strength was similar, 47 to 198 N (mean 123 N, SD 43 N). The adhesive failure usually occurred through the adhesive layer, however in two samples, at 167 N and 198 N the screw pulled out of the bone core. The fibrin tissue adhesive group reached a peak force of 8 N maximally at 2 hours (range 2.8-8 N, mean 5.4 N, SD 1.6 N). The mean BV/TV for femoral heads was 0.15 and indicates poor bone quality. CONCLUSION The bone adhesive successfully glued wet and fatty tissue of osteoporotic human bone cores. The mean ultimate pull-out force of 123 N at 24 hours corresponds to ∼ 300 kPa shear stress acting on the bone core. These first ex-vivo results in human bone are a promising step toward potential clinical application in osteochondral fragment fixation.

Summary Statement The chemistry, amount, morphology, and size distribution of wear debris from silicon nitride coatings generated in the bearing surface can potentially reduce the negative biological response and increase the longevity compared to conventional materials in joint replacements. Introduction Total hip implants have a high success rate at 15 years of implantation, but few survive over 25 years. At present, revisions are mostly due to aseptic loosening, believed to mainly be caused by the biological response to wear debris generated in the joint bearing. For the polymer liners the size of the wear debris determines the biological response, while for metal bearing surfaces a limitation is the metal ion release. When ceramics are used, the wear debris is in general small and mechanical factors may be the main cause for failure. A more recent, experimental alternative is to let the well-known metallic substrate serve as the soft, tough bulk, and additionally apply a hard and smooth ceramic coating. In this way a lower wear rate and reduced metal ion release could be obtained. Furthermore, the chosen composition, silicon nitride (SixNy), contains no detrimental ions, and silicon nitride debris has been shown to slowly dissolve in aqueous medium. Altogether, it can potentially increase the longevity of the implant. However, the debris from SixNy coatings has not yet been characterised. In this study, a wear model test was performed to generate wear debris from SixNy coatings. The debris was characterised using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) in combination with computational calculations. Methods Silicon nitride coatings deposited on flat cobalt chromium alloy (ASTM F75) were worn in a reciprocating ball on disc setup in a 25% serum solution at 37°C against an alumina ball with a load of 1.5 N. Wear debris was separated using serum digestion with hydrochloric acid (ISO 17853:2011) and examined in SEM in combination with EDS. As reference polyethylene (PE) was used to verify that relevant particles sizes were achieved. The SEM images were processed using a modified MATLAB-script originating from Cervera Gontard et al. [1], identifying the particles and calculating their size. Results Particles generated from SixNy coatings (n=62) a size distribution D50 [D10-D90] of 0.29 µm [0.16–0.69] and were round to oval in shape. The PE particles (n=70) had a size distribution of 0.29 µm [0.13–1.3], shaped similar to the SixNy particles or with a more elongated shape. Discussion and conclusions PE wear debris has been reported to lie in the size range of nm up to several μm in vivo, with a large proportion within the critical size for macrophage activation (0.2 to 0.8 μm). The model test reports relevant sizes and shape of PE debris, confirming the validity of the method. Particles generated from the SixNy coatings showed a smaller size range than PE, however most particles were within the critical size range for biological activation. In conclusion, this model test could be used to generate what we believe are relevant sizes and shapes of PE and SixNy wear debris and to learn more at an early stage of prediction of wear debris. Further dissolution studies as well as studies on the in vitro and in vivo cell response to these types of particles will be performed. The authors thank the Swedish Foundation for Strategic Research (SSF) through MS2E and FP7 NMP project LifeLongJoints for financial support, as well as Linkoping University for the coating facilities and expertise.

One of the major issues with the currently available injectable biomaterials for hard tissue replacement is the mismatch between their mechanical properties and those of the surrounding bone. Hybrid bone cements that combine the benefits of tough polymeric and bioactive ceramic materials could become a good alternative. In this work, polyhedral oligomeric silsesquioxane (POSS) was copolymerized with poly(ethylene glycol) (PEG) to form injectable in situ cross-linkable hybrid cements. The hybrids were characterized in terms of their mechanical, rheological, handling and in vitro bioactive properties. The results indicated that hybridization improves the mechanical and bioactive properties of POSS and PEG. The Young moduli of the hybrids were lower than those of commercial cements and more similar to those of cancellous bone. Furthermore, the strength of the hybrids was similar to that of commercial cements. Calcium deficient hydroxyapatite grew on the surface of the hybrids after 28 days in PBS, indicating bioactivity. The study showed that PEG-POSS-based hybrid materials are a promising alternative to commercial bone cements.

Interbody fusion aims to treat painful disc disease by demobilising the spinal segment through the use of an interbody fusion device (IFD). Diminished contact area at the endplate interface raises the risk of device subsidence, particularly in osteoporosis patients. The aim of the study was to ascertain whether vertebral body (VB) cement augmentation would reduce IFD subsidence following dynamic loading. Twenty-four human two-vertebra motion segments (T6–T11) were implanted with an IFD and distributed into three groups; a control with no cement augmentation; a second with PMMA augmentation; and a third group with calcium phosphate (CP) cement augmentation. Dynamic cyclic compression was applied at 1Hz for 24 hours in a specimen specific manner. Subsidence magnitude was calculated from pre and post-test micro-CT scans. The inferior VB analysis showed significantly increased subsidence in the control group (5.0±3.7mm) over both PMMA (1.6±1.5mm, p=.034) and CP (1.0±1.1mm, p=.010) cohorts. Subsidence in the superior VB to the index level showed no significant differences (control 1.6±3.0mm, PMMA 2.1±1.5mm, CP 2.2±1.2mm, p=.811). In the control group, the majority of subsidence occurred in the lower VB with the upper VB displaying little or no subsidence, which reflects the weaker nature of the superior endplate. Subsidence was significantly reduced in the lower VB when both levels were reinforced regardless of cement type. Both PMMA and CP cement augmentation significantly affected IFD subsidence by increasing VB strength within the motion segment, indicating that this may be a useful method for widening indications for surgical interventions in osteoporotic patients.

The still-growing field of additive manufacturing (AM), which includes 3D printing, has enabled manufacturing of patient-specific medical devices with high geometrical accuracy in a relatively quick manner. However, the development of materials with specific properties is still ongoing, including those for enhanced bone-repair applications. Such applications seek materials with tailored mechanical properties close to bone tissue and, importantly, that can serve as temporary supports, allowing for new bone ingrowth while the material is resorbed. Thus, controlling the resorption rate of materials for bone applications can support bone healing by balancing new tissue formation and implant resorption. In this regard, this work aimed to study the combination of polylactic acid (PLA), polycaprolactone (PCL) and hydroxyapatite (HA) to develop customized biocompatible and bioresorbable polymer-based composite filaments, through extrusion, for fused filament fabrication (FFF) printing. PLA ...

INTRODUCTION: Treatment of prosthesisrelated infection is difficult, and generally focuses on removal of the foreign body material combined with surgical removal of infected tissue around the prostheses area. Thereafter antibiotics are administrated. To reduce the incidence of infections and avoid systemic treatment, bone cements have been developed for local drug release (PMMA containing antibiotics). However, the release of antibiotics from PMMA generally consists of a burst release with little maintained elution. Furthermore, PMMA do not show bioactivity. Therefore, a combination of slow release of antibiotics with bioactivity would be a significant improvement of PMMA as bone cement. Via the addition of drug loaded bioactive calcium phosphate hollow spheres to PMMA a high drug loading capacity and good bioactivity can be achieved.

The structural integrity of cranial implants is of great clinical importance, as they aim to provide cerebral protection after neurosurgery or trauma. With the increased use of patient-specific implants, the mechanical response of each implant cannot be characterized experimentally in a practical way. However, computational models provide an excellent possibility for efficiently predicting the mechanical response of patient-specific implants. This study developed finite element models (FEMs) of titanium-reinforced calcium phosphate (CaP-Ti) implants. The models were validated with previously obtained experimental data for two different CaP-Ti implant designs (D1 and D2), in which generically shaped implant specimens were loaded in compression at either quasi-static (1 mm/min) or impact (5 kg, 1.52 m/s) loading rates. The FEMs showed agreement with experimental data in the force-displacement response for both implant designs. The implicit FEMs predicted the peak load with an underestimation for D1 (9%) and an overestimation for D2 (11%). Furthermore, the shape of the force-displacement curves were well predicted. In the explicit FEMs, the first part of the force-displacement response showed 5% difference for D1 and 2% difference for D2, with respect to the experimentally derived peak loads. The explicit FEMs efficiently predicted the maximum displacements with 1% and 4% difference for D1 and D2, respectively. Compared to the CaP-Ti implant, an average parietal cranial bone FEM showed a stiffer response, greater energy absorption and less deformation under the same impact conditions. The framework developed for modelling the CaP-Ti implants has a potential for modelling CaP materials in other composite implants in future studies since it only used literature based input and matched boundary conditions. Furthermore, the developed FEMs make an important contribution to future evaluations of patient-specific CaP-Ti cranial implant designs in various loading scenarios.

Ceramic materials are sometimes used as bearing surfaces of joint implants due to their high wear resistance and biocompatibility. Silicon nitride (Si3N4) is one of the ceramics under investigation for such use, owing to its bacteriostatic properties and high wear resistance. Traditional Si3N4 is sintered using Al2O3 and Y2O3 as sintering aids. To improve the biocompatibility and bioactivity of Si3N4, new sintering aids (SrO, MgO, and SiO2) were used in this work. This substitution may however have substantial effects on the wear properties of the material. Hence, the aim of this study was to evaluate these effects. Multidirectional pin-on-disc wear tests against ultra-high molecular weight polyethylene pins were used to this end, running in fetal bovine serum solution at 37 °C for 2 million cycles. The surface roughness, phase composition, and surface morphology of the surfaces were investigated, together with the pH of the wear test lubricant and compared to a traditional Si3N4 co...

Nowadays titanium alloys are extensively used for aerospace and biomedical applications. However, despite good mechanical properties and excellent corrosion resistance they possess poor wear resistance and a tendency to galling and seizure. In this study the tribological properties of experimental Ti-Si-Zr based alloys were studied using a standard ball-on-disc wear testing system. The wear and friction tests were conducted in bovine serum solution under room temperature using silicon nitride balls as counter-bodies. Measurements of friction coefficients and volumetric wear rates were made and microscopic investigations of the wear tracks were performed along with examination of structure and properties using light microscopy, XRD, SEM and hardness testing.

The aim of this study was to evaluate skull replacement options after decompressive craniectomy by systematically investigating which combination of geometrical properties and material selection would result in a mechanical response comparable in stiffness to that of native skull bone and a strength as high or higher than the same. The study was conducted using a Finite Element Model of the top part of a human skull. Native skull bone, autografts and commercial implants made of PEEK, solid titanium, two titanium meshes and a titanium-ceramic composite were modeled under a set load to evaluate deformation and maximum stress. The computational result showed a large variation of the strength and effective stiffness of the autografts and implants. The stiffness of native bone varied by a factor of 20 and the strength by a factor of eight. The implants span the entire span of the native skull, both in stiffness and strength. All the investigated implant materials had a potential for havi...

For more than 50 years total hip replacements have been a common and successful procedure to increase patient mobility and quality of life. The 10-year implant survival rate is 97.8%. However, for longer implantation times there are limitations linked to the negative biological response to wear and corrosion products from the currently used biomaterials.In this thesis silicon nitride (SiNx) coatings were evaluated for use in total hip replacements, on the articulating bearing surface and modular taper connections. Homogeneous, dense SiNx coatings were deposited using reactive high power impulse magnetron sputtering (HiPIMS) up to a thickness of 8 µm. The N/Si atomic ratios ranged from 0.3 to 1.1 and the coatings showed a low surface roughness. The wear rate of a SiNx coated cobalt chromium molybdenum alloy (CoCrMo) was similar to that of bulk Si3N4, and less than one 46th of uncoated CoCrMo, an alloy that is commonly used in joint replacements. Wear debris generated from SiNx coatin...

The addition of alloying elements, in particular chromium, reduced the dissolution rate of silicon nitride coatings without affecting other functional properties such as hardness. Optimum chromium contents gave an enhanced in vitro cell viability.

Cement discoplasty has been developed to treat patients with advanced intervertebral disc degeneration. In discoplasty, poly(methylmethacrylate) (PMMA) bone cement is injected into the disc, leading to reduced pain and certain spinal alignment correction. Standard PMMA-cements have much higher elastic modulus than the surrounding vertebral bone, which may lead to a propensity for adjacent fractures. A PMMA-cement with lower modulus might be biomechanically beneficial. In this study, PMMA-cements with lower modulus were obtained using previously established methods. A commercial PMMA-cement (V-steady®, G21 srl) was used as control, and as base cement. The low-modulus PMMA-cements were modified by 12 vol% (LA12), 16 vol% (LA16) and 20 vol% (LA20) linoleic acid (LA). After storage in 37 °C PBS from 24 h up to 8 weeks, specimens were tested in compression to obtain the material properties. A lower E-modulus was obtained with increasing amount of LA. However, with storage time, the E-mod...

Powder Bed Fusion–Laser Beam (PBF–LB) processing of magnesium (Mg) alloys is gaining increasing attention due to the possibility of producing complex biodegradable implants for improved healing of large bone defects. However, the understanding of the correlation between the PBF–LB process parameters and the microstructure formed in Mg alloys remains limited. Thus, the purpose of this study was to enhance the understanding of the effect of the PBF–LB process parameters on the microstructure of Mg alloys by investigating the applicability of computational thermodynamic modelling and verifying the results experimentally. Thus, PBF–LB process parameters were optimized for a Mg WE43 alloy (Mg-Y3.9 wt%-Nd3 wt%-Zr0.5 wt%) on a commercially available machine. Two sets of process parameters successfully produced sample densities > 99.4%. Thermodynamic computations based on the Calphad method were employed to predict the phases present in the processed material. Phases experimentally estab...

Ceramic coatings may prolong the lifetime of joint implants. Certain ions and wear debris may however lead to negative biological effects. SiN-based materials may substantially reduce these effects, but still need optimization for the application. In this study, a combinatorial deposition method enabled an efficient evaluation of a range of Si–Fe–C–N coating compositions on the same sample. The results revealed compositional gradients of Si (26.0–33.9 at.%), Fe (9.6–20.9 at.%), C (8.2–13.9 at.%) and N (39.7–47.2 at.%), and low oxygen contaminations (0.3–0.6 at.%). The mechanical properties varied with a hardness (H) ranging between 13.7–17.3 GPa and an indentation modulus (M) between 190–212 GPa. Both H and M correlated with the Si (H and M increased as Si increased) and Fe (H and M decreased as Fe increased) content. A slightly columnar morphology was observed in cross-sections, as well as a surface roughness in the nm range. A cell study revealed adhering pre-osteogenic MC3T3 cell...