Blueprints for the Next Generation of Bioinspired and Biomimetic Mineralised Composites for Bone Regeneration.

Coccolithophores are unicellular marine phytoplankton, which produce intricate, tightly regulated, exoskeleton calcite structures. The formation of biogenic calcite occurs either intracellularly, forming 'wheel-like' calcite plates, or extracellularly, forming 'tiled-like' plates known as coccoliths. Secreted coccoliths then self-assemble into multiple layers to form the coccosphere, creating a protective wall around the organism. The cell wall hosts a variety of unique species-specific inorganic morphologies that cannot be replicated synthetically. Although biomineralisation has been extensively studied, it is still not fully understood. It is becoming more apparent that biologically controlled mineralisation is still an elusive goal. A key question to address is how nature goes from basic building blocks to the ultrafine, highly organised structures found in coccolithophores. A better understanding of coccolithophore biomineralisation will offer new insight into biomimetic and bioinspired synthesis of advanced, functionalised materials for bone tissue regeneration. The purpose of this review is to spark new interest in biomineralisation and gain new insight into coccolithophores from a material science perspective, drawing on existing knowledge from taxonomists, geologists, palaeontologists and phycologists.

Biocompatibility of calcium phosphate bone cement with optimised mechanical properties: an in vivo study.

This work establishes the in vivo performance of modified calcium phosphate bone cements for vertebroplasty of spinal fractures using a lapine model. A non-modified calcium phosphate bone cement and collagen-calcium phosphate bone cements composites with enhanced mechanical properties, utilising either bovine collagen or collagen from a marine sponge, were compared to a commercial poly(methyl methacrylate) cement. Conical cement samples (8 mm height × 4 mm base diameter) were press-fit into distal femoral condyle defects in New Zealand White rabbits and assessed after 5 and 10 weeks. Bone apposition and tartrate-resistant acid phosphatase activity around cements were assessed. All implants were well tolerated, but bone apposition was higher on calcium phosphate bone cements than on poly(methyl methacrylate) cement. Incorporation of collagen showed no evidence of inflammatory or immune reactions. Presence of positive tartrate-resistant acid phosphatase staining within cracks formed in calcium phosphate bone cements suggested active osteoclasts were present within the implants and were actively remodelling within the cements. Bone growth was also observed within these cracks. These findings confirm the biological advantages of calcium phosphate bone cements over poly(methyl methacrylate) and, coupled with previous work on enhancement of mechanical properties through collagen incorporation, suggest collagen-calcium phosphate bone cement composite may offer an alternative to calcium phosphate bone cements in applications where low setting times and higher mechanical stability are important.

In Vitro Degradation of 3D-Printed Poly(L-lactide-Co-Glycolic Acid) Scaffolds for Tissue Engineering Applications.

The creation of scaffolds for cartilage tissue engineering has faced significant challenges in developing constructs that can provide sufficient biomechanical support and offer suitable degradation characteristics. Ideally, such tissue-engineering techniques necessitate the fabrication of scaffolds that mirror the mechanical characteristics of the articular cartilage while degrading safely without damaging the regenerating tissues. The aim of this study was to create porous, biomechanically comparable 3D-printed scaffolds made from Poly(L-lactide-co-glycolide) 85:15 and to assess their degradation at physiological conditions 37 °C in pH 7.4 phosphate-buffered saline (PBS) for up to 56 days. Furthermore, the effect of scaffold degradation on the cell viability and proliferation of human bone marrow mesenchymal stem cells (HBMSC) was evaluated in vitro. To assess the long-term degradation of the scaffolds, accelerated degradation tests were performed at an elevated temperature of 47 °C for 28 days. The results show that the fabricated scaffolds were porous with an interconnected architecture and had comparable biomechanical properties to native cartilage. The degradative changes indicated stable degradation at physiological conditions with no significant effect on the properties of the scaffold and biocompatibility of the scaffold to HBMSC. Furthermore, the accelerated degradation tests showed consistent degradation of the scaffolds even in the long term without the notable release of acidic byproducts. It is hoped that the fabrication and degradation characteristics of this scaffold will, in the future, translate into a potential medical device for cartilage tissue regeneration.

Evaluation of the in vitro cytotoxicity and modulation of the inflammatory response by the bioresorbable polymers poly(D,L-lactide-co-glycolide) and poly(L-lactide-co-glycolide).

Bioresorbable polymers composed of poly(D,L-lactide-co-glycolide) (PDLLGA) and poly(L-lactide-co-glycolide) (PLLGA) have become increasingly popular for the preparation of bone substitute constructs. However, there are reports of a delayed inflammatory reaction occurring months or years after implantation. Due to the long polymer degradation times, in vitro tests carried out at physiological temperature, 37°C, tend to assess only the short-term biocompatibility of these materials. The aim of this work is to develop an in vitro protocol that can be used to assess the long-term cytotoxicity of bioresorbable polymers in a time efficient manner. This study used a previously developed and validated accelerated degradation protocol to obtain samples of PDLLGA and PLLGA at increasing levels of degradation. Samples were then applied to standard ISO 10993-5 direct contact cytotoxicity testing and it was found that PDLLGA samples showed increasing levels of cytotoxicity at the later stages of degradation, with PLLGA samples demonstrating significantly less cytotoxic behaviour. Following concern that accumulation of acidic degradation products in a closed multi-well culture environment could overestimate cytotoxicity, we developed and validated a new dynamic flow culture methodology, for testing the cytotoxicity of these degradable materials, by adapting a commercial "organ on a chip" flow culture system, Quasi Vivo®. In addition to cytotoxicity testing, we have carried out profiling of inflammatory cytokines released by cells in response to degraded PDLLGA and PLLGA, and have suggested mechanism by which lactide-based bioresorbable materials could modulate the inflammatory response through the G-protein coupled receptor (GPCR), hydroxycarboxylic acid receptor 1 (HCA1). STATEMENT OF SIGNIFICANCE: Bioresorbable materials naturally disintegrate over time when implanted into the body. They are often used to make screws and clips for repair of broken bones. Unfortunately, some patients can react badly to the material, resulting in painful inflammation. Biomaterials scientists are interested in developing materials that are more compatible with the body. However, it is very difficult to predict the long-term compatibility of bioresorbable materials in the lab. In our study, we have developed a method that will allow us to study the effects of the materials as they continue to break down. This will help us understand why the materials may cause inflammation, and will support research into the development of new and improved materials for bone repair.

3D-printed patient-specific pelvis phantom for dosimetry measurements for prostate stereotactic radiotherapy with dominant intraprostatic lesion boost.

AIM: Developing and assessing the feasibility of using a three-dimensional (3D) printed patient-specific anthropomorphic pelvis phantom for dose calculation and verification for stereotactic ablative radiation therapy (SABR) with dose escalation to the dominant intraprostatic lesions. MATERIAL AND METHODS: A 3D-printed pelvis phantom, including bone-mimicking material, was fabricated based on the computed tomography (CT) images of a prostate cancer patient. To compare the extent to which patient and phantom body and bones overlapped, the similarity Dice coefficient was calculated. Modular cylindrical inserts were created to encapsulate radiochromic films and ionization chamber for absolute dosimetry measurements at the location of prostate and at the boost region. Gamma analysis evaluation with 2%/2mm criteria was performed to compare treatment planning system calculations and measured dose when delivering a 10 flattening filter free (FFF) SABR plan and a 10FFF boost SABR plan. RESULTS: Dice coefficients of 0.98 and 0.91 were measured for body and bones, respectively, demonstrating agreement between patient and phantom outlines. For the boost plans the gamma analysis yielded 97.0% of pixels passing 2%/2mm criteria and these results were supported by the chamber average dose difference of 0.47 ± 0.03%. These results were further improved when overriding the bone relative electron density: 97.3% for the 2%/2mm gamma analysis, and 0.05 ± 0.03% for the ionization chamber average dose difference. CONCLUSIONS: The modular patient-specific 3D-printed pelvis phantom has proven to be a highly attractive and versatile tool to validate prostate SABR boost plans using multiple detectors.

Influence of surface condition on the degradation behaviour and biocompatibility of additively manufactured WE43.

The further development of future Magnesium based biodegradable implants must consider not only the freedom of design, but also comprise implant volume reduction, as both aspects are crucial for the development of higher functionalised implants, such as plate systems or scaffold grafts in bone replacement therapy. As conventional manufacturing methods such as turning and milling are often accompanied by limitations concerning implant design and functionality, the process of laser powder bed fusion (LPBF) specifically for Magnesium alloys was recently introduced. In addition, the control of the degradation rate remains a key aspect regarding biodegradable implants. Recent studies focusing on the degradation behaviour of additively manufactured Magnesium scaffolds disclosed additional intricacies when compared to conventionally manufactured Magnesium parts, as a notably larger surface area was exposed to the immersion medium and scaffold struts degraded non-uniformly. Moreover, chemical etching as post processing technique is applied to remove sintered powder particles from the surface, altering surface chemistry. In this study, cylindrical Magnesium specimens were manufactured by LPBF and surfaces were consecutively modified by phosphoric etching and machining. Degradation behaviour and biocompatibility were then investigated, revealing that etched samples exhibited the overall lowest degradation rates, but experienced large pit formation, while the reduction of surface roughness resulted in a delay of degradation.

Special issue: select papers from the 29th Northern Ireland Biomedical Engineering Conference, Belfast, UK, April 2009.

Each year, NIBES hosts a spring conference that is jointly organised by Queen's University of Belfast and University of Ulster. The 29th NIBES Spring meeting took place on 8th April 2009 at Queen's University of Belfast. NIBES 2009 had an impressive scientific program with two international leading plenary speakers and 28 oral presentations.

Hydroxyapatite bone substitutes developed via replication of natural marine sponges.

The application of synthetic cancellous bone has been shown to be highly successful when its architecture mimics that of the naturally interconnected trabeculae bone it aims to replace. The following investigation demonstrates the potential use of marine sponges as precursors in the production of ceramic based tissue engineered bone scaffolds. Three species of natural sponge, Dalmata Fina (Spongia officinalis Linnaeus, Adriatic Sea), Fina Silk (Spongia zimocca, Mediterranean) and Elephant Ear (Spongia agaricina, Caribbean) were selected for replication. A high solid content (80 %wt), low viscosity (126 mPas) hydroxyapatite slurry was developed, infiltrated into each sponge species and subsequently sintered, producing a scaffold structure that replicated pore architecture and interconnectivity of the precursor sponge. The most promising of the ceramic tissue engineered bone scaffolds developed, Spongia agaricina replicas, demonstrated an overall porosity of 56-61% with 83% of the pores ranging between 100 and 500 microm (average pore size 349 microm) and an interconnectivity of 99.92%.

Performance of calcium deficient hydroxyapatite-polyglycolic acid composites: an in vitro study.

The strategic incorporation of bioresorbable polymeric additives to calcium-deficient hydroxyapatite cement may provide short-term structural reinforcement and modify the modulus to closer match bone. The longer-term resorption properties may also be improved, creating pathways for bone in-growth. The aim of this study was to investigate the resorption process of a calcium phosphate cement system containing either in polyglycolic acid tri-methylene carbonate particles or polyglycolic acid fibres. This was achieved by in vitro aging in physiological conditions (phosphate buffered solution at 37 degrees C) over 12 weeks. The unreinforced CPC exhibited an increase in compressive strength at 12 weeks, however catastrophic failure was observed above a critical loading. The fracture behaviour of cement was improved by the incorporation of PGA fibres; the cement retained its cohesive structure after critical loading. Gravimetric analysis and scanning electron microscopy showed a large proportion of the fibres had resorbed after 12 weeks allowing for the increased cement porosity, which could facilitate cell infiltration and faster integration of natural bone. Incorporating the particulate additives in the cement did not provide any mechanism for mechanical property augmentation or did not demonstrate any appreciable level of resorption after 12 weeks.

In vitro testing of chitosan in gentamicin-loaded bone cement: no antimicrobial effect and reduced mechanical performance.

BACKGROUND AND PURPOSE: Efforts to prevent infection of arthroplasties, including the use of antibiotic-loaded bone cement, are not always successful. We investigated whether the incorporation of chitosan in gentamicin-loaded bone cement increases antibiotic release, and prevents bacterial adherence and biofilm formation by clinical isolates of Staphylococcus spp. In addition, we performed mechanical and degradation tests. METHODS: Different amounts of chitosan were added to the powder of the gentamicin-loaded bone cement. Gentamicin release was determined using high-per-formance liquid chromatography mass spectrometry. Bacterial adherence and bacterial biofilm formation were determined using clinical isolates cultured from implants retrieved at revision hip surgery. The mechanical properties were determined as a function of degradation in accordance with ISO and ASTM standards for PMMA bone cement. RESULTS: The addition of chitosan to bone cement loaded with gentamicin reduced gentamicin release and did not increase the efficacy of the bone cement in preventing bacterial colonization and biofilm formation. Moreover, the mechanical performance of cement containing chitosan was reduced after 28 days of degradation. The compressive and bending strengths were not in compliance with the minimum ISO and ASTM requirements. INTERPRETATION: Clinically, incorporation of chitosan into gentamicin-loaded bone cement for use in joint replacement surgery has no antimicrobial benefit and the detrimental effect on mechanical properties may have an adverse effect on the longevity of the prosthetic joint.

Development of three-dimensional printing polymer-ceramic scaffolds with enhanced compressive properties and tuneable resorption.

In this study, bone tissue engineered scaffolds fabricated via powder-based 3D printing from hydroxyapatite (HA) and calcium sulphate (CaSO4) powders were investigated. The combination of using a fast resorbing CaSO4 based powder and the relatively slower HA powder represents a promising prospect for tuning the bioresorption of 3D printed (3DP) scaffolds. These properties could then be tailored to coincide with tissue growth rate for different surgical procedures. The manufactured scaffolds were infiltrated with poly(ε­caprolactone) (PCL). The PCL infiltrated the inter-particle spacing within the 3DP structures due to the nature of a loosely-packed powder bed and also covered the surface of ceramic-based scaffolds. Consequently, the average compressive strength, compressive modulus and toughness increased by 314%, 465% and 867%, respectively. The resorption behaviour of the 3DP scaffolds was characterised in vitro using a high-throughput system that mimicked the physiological environment and dynamic flow conditions relevant to the human body. A rapid release of CaSO4 between Day 0 and 28 was commensurate with a reduction in scaffold mass and compressive properties, as well as an increase in medium absorption. In spite of this, HA particles, connected by PCL fibrils, remained within the microstructure after 56 days resorption under dynamic conditions. Consequently, a high level of structural integrity was maintained within the 3DP scaffold. This study presented a porous PCL-HA-CaSO4 3DP structure with the potential to encourage new tissue growth during the initial stages of implantation and also offering sufficient structural and mechanical support during the bone healing phase.

Orthopaedic tissue engineering and bone regeneration.

Orthopaedic tissue engineering combines the application of scaffold materials, cells and the release of growth factors. It has been described as the science of persuading the body to reconstitute or repair tissues that have failed to regenerate or heal spontaneously. In the case of bone regeneration 3-D scaffolds are used as a framework to guide tissue regeneration. Mesenchymal cells obtained from the patient via biopsy are grown on biomaterials in vitro and then implanted at a desired site in the patient's body. Medical implants that encourage natural tissue regeneration are generally considered more desirable than metallic implants that may need to be removed by subsequent intervention. Numerous polymeric materials, from natural and artificial sources, are under investigation as substitutes for skeletal elements such as cartilage and bone. For bone regeneration, cells (obtained mainly from bone marrow aspirate or as primary cell outgrowths from bone biopsies) can be combined with biodegradable polymeric materials and/or ceramics and absorbed growth factors so that osteoinduction is facilitated together with osteoconduction; through the creation of bioactive rather than bioinert scaffold constructs. Relatively rapid biodegradation enables advantageous filling with natural tissue while loss of polymer strength before mass is disadvantageous. Innovative solutions are required to address this and other issues such as the biocompatibility of material surfaces and the use of appropriate scaffold topography and porosity to influence bone cell gene expression.

Surrogate Outcome Measures of In Vitro Osteoclast Resorption of ß Tricalcium Phosphate.

Introduction of porosity to calcium phosphate scaffolds for bone repair has created a new challenge when measuring bioresorption in vitro, rendering traditional outcome measures redundant. The aim of this study is to identify a surrogate endpoint for use with 3D scaffolds. Murine RAW 264.7 cells are cultured on dense discs of ß-tricalcium phosphate in conditions to stimulate osteoclast (OC) formation. Multinucleated OCs are visible from day 6 with increases at days 8 and 10. Resorption pits are first observed at day 6 with much larger pits visible at days 8, 10, and 12. The concentration of calcium ions in the presence of cells is significantly higher than cell-free cultures at days 3 and 9. Using linear regression analysis, Ca ion release could account for 35.9% of any subsequent change in resorption area. The results suggest that Ca ion release is suitable to measure resorption of a beta-tricalcium phosphate ceramic substrate in vitro. This model could replace the more accepted resorption pit assay in circumstances where quantification of pits is not possible, e.g., when characterizing 3D tissue engineered bone scaffolds.

Effects of poly (ε-caprolactone) coating on the properties of three-dimensional printed porous structures.

Powder-based inkjet three-dimensional printing (3DP) to fabricate pre-designed 3D structures has drawn increasing attention. However there are intrinsic limitations associated with 3DP technology due to the weak bonding within the printed structure, which significantly compromises its mechanical integrity. In this study, calcium sulphate ceramic structures demonstrating a porous architecture were manufactured using 3DP technology and subsequently post-processed with a poly (ε-caprolactone) (PCL) coating. PCL concentration, immersion time, and number of coating layers were the principal parameters investigated and improvement in compressive properties was the measure of success. Interparticle spacing within the 3DP structures were successfully filled with PCL material. Consequently the compressive properties, wettability, morphology, and in vitro resorption behaviour of 3DP components were significantly augmented. The average compressive strength, Young׳s modulus, and toughness increased 217%, 250%, and 315%, following PCL coating. Addition of a PCL surface coating provided long-term structural support to the host ceramic material, extending the resorption period from less than 7 days to a minimum of 56 days. This study has demonstrated that application of a PCL coating onto a ceramic 3DP structure was a highly effective approach to addressing some of the limitations of 3DP manufacturing and allows this advanced technology to be potentially used in a wider range of applications.

Biocompatibility of calcium phosphate bone cement with optimized mechanical properties.

The broad aim of this work was to investigate and optimize the properties of calcium phosphate bone cements (CPCs) for use in vertebroplasty to achieve effective primary fixation of spinal fractures. The incorporation of collagen, both bovine and from a marine sponge (Chondrosia reniformis), into a CPC was investigated. The biological properties of the CPC and collagen-CPC composites were assessed in vitro through the use of human bone marrow stromal cells. Cytotoxicity, proliferation, and osteoblastic differentiation were evaluated using lactate dehydrogenase, PicoGreen, and alkaline phosphatase activity assays, respectively. The addition of both types of collagen resulted in an increase in cytotoxicity, albeit not to a clinically relevant level. Cellular proliferation after 1, 7, and 14 days was unchanged. The osteogenic potential of the CPC was reduced through the addition of bovine collagen but remained unchanged in the case of the marine collagen. These findings, coupled with previous work showing that incorporation of marine collagen in this way can improve the physical properties of CPCs, suggest that such a composite may offer an alternative to CPCs in applications where low setting times and higher mechanical stability are important.

The effect of patient gait on the material properties of UHMWPE in hip replacements.

The wear of ultra-high molecular weight polyethylene (UHMWPE) acetabular components in total hip replacements (THRs) has been shown to be highly dependent on the direction of shear. Greatly reduced wear rates have been reported for unidirectional, compared to multidirectional, articulation in vitro. This work for the first time enables investigation of a relationship between clinical wear conditions, as determined by patient gait path, and the mechanical and structural changes that occur within the UHMWPE acetabular component. Individual patients' wear paths were determined prior to revision operation from hip joint kinematics measured by clinical gait analysis. The material properties of the acetabular components removed during the revision operation were subsequently analysed. A technique using Fourier transform infra- red analysis (FTIR) was developed to quantify the orientation of the individual UHMWPE lamellae. This study shows that there is a direct relationship between a patient's clinical gait path and the molecular properties of their UHMWPE acetabular socket. Patient kinematics are an important factor affecting the wear and long-term biocompatibility of UHMWPE used as a bearing surface in THR.

Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics.

A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells. STATEMENT OF SIGNIFICANCE: The evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS).

Endovascular aneurysm repair: is imaging surveillance robust, and does it influence long-term mortality?

PURPOSE: Endovascular aneurysm repair (EVAR) is the dominant treatment strategy for abdominal aortic aneurysms. However, as a result of uncertainty regarding long-term durability, an ongoing imaging surveillance program is required. The aim of the study was to assess EVAR surveillance in Scotland and its effect on all-cause and aneurysm-related mortality. METHODS: A retrospective analysis of all EVAR procedures carried out in the four main Scottish vascular units. The primary outcome measure was the implementation of post-EVAR imaging surveillance across Scotland. Patients were identified locally and then categorized as having complete, incomplete, or no surveillance. Secondary outcome measures were all-cause mortality and aneurysm-related mortality. Cause of death was obtained from death certificates. RESULTS: Data were available for 569 patients from the years 2001 to 2012. All centers had data for a minimum of 5 contiguous years. Surveillance ranged from 1.66 to 4.55 years (median 3.03 years). Overall, 53 % had complete imaging surveillance, 43 % incomplete, and 4 % none. For the whole cohort, all-cause 5-year mortality was 33.5 % (95 % confidence interval 28.0-38.6) and aneurysm-related mortality was 4.5 % (.8-7.3). All-cause mortality in patients with complete, incomplete, and no imaging was 49.9 % (39.2-58.6), 19.1 % (12.6-25.2), and 47.2 % (17.7-66.2), respectively. Aneurysm-related mortality was 3.7 % (1.8-7.4), 4.4 % (2.2-8.9), and 9.5 % (2.5-33.0), respectively. All-cause mortality was significantly higher in patients with complete compared to incomplete imaging surveillance (p < 0.001). No significant differences were observed in aneurysm-related mortality (p = 0.2). CONCLUSION: Only half of EVAR patients underwent complete long-term imaging surveillance. However, incomplete imaging could not be linked to any increase in mortality. Further work is required to establish the role and deliverability of EVAR imaging surveillance.

Printability of calcium phosphate: calcium sulfate powders for the application of tissue engineered bone scaffolds using the 3D printing technique.

In this study, calcium phosphate (CaP) powders were blended with a three-dimensional printing (3DP) calcium sulfate (CaSO4)-based powder and the resulting composite powders were printed with a water-based binder using the 3DP technology. Application of a water-based binder ensured the manufacture of CaP:CaSO4 constructs on a reliable and repeatable basis, without long term damage of the printhead. Printability of CaP:CaSO4 powders was quantitatively assessed by investigating the key 3DP process parameters, i.e. in-process powder bed packing, drop penetration behavior and the quality of printed solid constructs. Effects of particle size, CaP:CaSO4 ratio and CaP powder type on the 3DP process were considered. The drop penetration technique was used to reliably identify powder formulations that could be potentially used for the application of tissue engineered bone scaffolds using the 3DP technique. Significant improvements (p<0.05) in the 3DP process parameters were found for CaP (30-110 µm):CaSO4 powders compared to CaP (<20 µm):CaSO4 powders. Higher compressive strength was obtained for the powders with the higher CaP:CaSO4 ratio. Hydroxyapatite (HA):CaSO4 powders showed better results than beta-tricalcium phosphate (ß-TCP):CaSO4 powders. Solid and porous constructs were manufactured using the 3DP technique from the optimized CaP:CaSO4 powder formulations. High-quality printed constructs were manufactured, which exhibited appropriate green compressive strength and a high level of printing accuracy.

Experimental and computational approach investigating burst fracture augmentation using PMMA and calcium phosphate cements.

The aim of the study was to use a computational and experimental approach to evaluate, compare and predict the ability of calcium phosphate (CaP) and poly (methyl methacrylate) (PMMA) augmentation cements to restore mechanical stability to traumatically fractured vertebrae, following a vertebroplasty procedure. Traumatic fractures (n = 17) were generated in a series of porcine vertebrae using a drop-weight method. The fractured vertebrae were imaged using µCT and tested under axial compression. Twelve of the fractured vertebrae were randomly selected to undergo a vertebroplasty procedure using either a PMMA (n = 6) or a CaP cement variation (n = 6). The specimens were imaged using µCT and re-tested. Finite element models of the fractured and augmented vertebrae were generated from the µCT data and used to compare the effect of fracture void fill with augmented specimen stiffness. Significant increases (p < 0.05) in failure load were found for both of the augmented specimen groups compared to the fractured group. The experimental and computational results indicated that neither the CaP cement nor PMMA cement could completely restore the vertebral mechanical behavior to the intact level. The effectiveness of the procedure appeared to be more influenced by the volume of fracture filled rather than by the mechanical properties of the cement itself.