Introduction. The surgical treatment of critical-sized bone defects with complex three-dimensional (3D) geometries is a challenge for the treating surgeon. Additive manufacturing such as 3D printing enables the production of highly individualized bone implants meeting the shape of the patient's bone defect and including a tunable internal structure. In this study, we showcase the design process for patient-specific implants with critical-sized tibia defects. Methods. Two clinical cases of patients with critical tibia defects (size 63×20×21 mm and 50×24×17 mm) were chosen. Brainlab software was used for segmentation of CT data generating 3D models of the defects. The implant construction involves multiple stages. Initially, the outer shell is precisely defined. Subsequently, the specified volume is populated with internal structures using Voronoi, Gyroid, and NaCl crystal structures. Variation in pore size (1.6 mm and 1.0 mm) was accomplished by adjusting scaffold size and material thickness. Results. An algorithmic design process in Rhino and Grasshopper was successfully applied to generate model implants for the tibia from Ct data. By integrating a precise mesh into an outer shell, a scaffold with controlled porosity was designed. In terms of the internal design, both Voronoi and Gyroid form macroscopically homogeneous properties, while NaCl, exhibits irregularities in density and consequently, in the strength of the structure. Data implied that Voronoi and Gyroid structures adapt more precisely to complex and irregular outer shapes of the implants. Conclusion. In proof-of-principle studies customized tibia implants were successfully generated and printed as model implants based on resin. Further studies will include more patient data sets to refine the workflows and digital tools for a broader spectrum of bone defects. The algorithm-based design might offer a tremendous potential in terms of an automated design process for 3D printed implants which is essential for clinical application

Intramedullary nails (IMNs) are the current gold standard for treatment of long bone diaphyseal and selected metaphyseal fractures. Their design has undergone many revisions to improve fixation techniques, conform to the bone shape with appropriate anatomic fit, reduce operative time and radiation exposure, and extend the indication of the same implant for treatment of different fracture types with minimal soft tissue irritation. The IMNs are made or either titanium alloy or stainless steel and work as load-sharing internal splints along the long bone, usually accommodating locking elements – screws and blades, often featuring angular stability and offering different configurations for multiplanar fixation – to secure secondary fracture healing with callus formation in a relative-stability environment. Bone cement augmentation of the locking elements can modulate the construct stiffness, increase the surface area at the bone-implant interface, and prevent cut-through of the locking elements. The functional requirements of IMNs are related to maintaining fracture reduction in terms of length, alignment and rotation to enhance fracture healing. The load distribution during patient's activities is along the entire bone-nail interface, with nail length and anatomic fit being important factors to avoid stress risers

Osteosarcoma is a highly malignant primary tumor of bone tissue. The 5-year survival rate of patients with metastasis is below 20% and this scenario is unchanged in the last two decades, despite great efforts in pre-clinical and clinical research. Traditional preclinical models of osteosarcoma do not consider the whole complexity of its microenvironment, leading to poor correlation between in vitro/in vivo results and clinical outcomes. Spheroids are a promising in vitro model to mimic osteosarcoma and perform drug-screening tests, as they (i) reproduce the microarchitecture of the tumor, (ii) are characterized by hypoxic regions and necrotic core as the in vivo tumor, (iii) and recapitulate the chemo-resistance phenomena. However, to date, the spheroid model is scarcely used in osteosarcoma research. Our aim is to develop a customized culture dish to grow and characterize spheroids and to perform advanced drug-screening tests. The resulting platform must be adapted to automated image acquisition systems, to overcome the drawbacks of commercial spheroids platforms. To this purpose, we designed and developed a micro-patterned culture dish by casting agarose on a 3D printed mold from a CAD design. We successfully obtained viable and reproducible homotypic osteosarcoma spheroids, with two different cells lines from osteosarcoma (i.e., 143b and MG-63). Using the platform, we performed viability assays and live fluorescent stainings (e.g., Calcein AM) with low reagent consumption. Moreover, the culture dish was validated as drug screening platform, administrating Doxorubicin at different doses, and evaluating its effect on OS spheroids, in terms of morphology and viability. This platform can be considered an attractive alternative to the highly expensive commercial spheroid platforms to obtain homogeneous and reproducible spheroids in a high-throughput and cost effective mode

The anatomy of the femur shows a high inter-patient variability, making it challenging to design standard prosthetic devices that perfectly adapt to the geometry of each individual. Over the past decade, Statistical Shape Models (SSMs) have been largely used as a tool to represent an average shape of many three-dimensional objects, as well as their variation in shape. However, no studies of the morphology of the residual femoral canal in patients who have undergone an amputation have been performed. The aim of this study was therefore to evaluate the main modes of variation in the shape of the canal, therefore simulating and analysing different levels of osteotomy. To assess the variability of the femoral canal, 72 CT-scans of the lower limb were selected. A segmentation was performed to isolate the region of interest (ROI), ranging from the lesser tip of the trochanter to the 75% of the length of the femur. The canals were then sized to scale, aligned, and 16 osteotomy levels were simulated, starting from a section corresponding to 25% of the ROI and up to the distal section. For each level, the main modes of variations of the femoral canal were identified through Principal Component Analysis (PCA), thus generating the mean geometry and the extreme shapes (±2 stdev) of the principal modes of variation. The shape of the canals obtained from these geometries was reconstructed every 10 mm, best- fitted with an ellipse and the following parameters were evaluated: i) ellipticity, by looking at the difference between axismax and axismin; ii) curvature of the canal, calculating the arc of circumference passing through the shapes’ centroids; iii) conicity, by looking at the maximum/minimum diameter; iv) mean diameter. To understand the association between the main modes and the shape variance, these parameters were compared, for each level of osteotomy, between the two extreme geometries of the main modes of variation. Results from PCA pointed out that the first three PCs explained more than the 87% of the total variance, for each level of simulated osteotomy. By analysing the extreme geometries for a distal osteotomy (e.g. 80% of the length of the canal), the first PC was associated to a combination of ROC (var%=41%), conicity (var%=28%) and ellipticity (var%=7%). PC2 was still associated with the ROC (var%=16%), while PC3 turned out to be associated with the diameter (var%=38%). Through the SSM presented in this study, a quantitatively evaluation of the deformation of the intramedullary canal has been made possible. By analysing the extreme geometries obtained from the first three modes of variance, it is clear that the first three PCs accounted for the variations in terms of curvature, conicity, ellipticity and diameter of the femoral canal with a different weight, depending on the level of osteotomy. Through this work, it was also possible to parametrize these variations according to the level of excision. The results given for the segment corresponding to the 80% of the length of the canal showed that, at that specified level, the ROC, conicity and ellipticity were the anatomical parameters with the highest range of variability, followed by the variation in terms of diameter. Therefore, the analysis carried out can provide information about the relevance of these parameters depending on the level of osteotomy suffered by the amputee. In this way, optimal strategies for the design and/or customization of osteo-integrated stems can be offered depending on the patient's residual limb

Abstract. Objectives. Young patients receiving metallic bone implants after surgical resection of bone cancer require implants that last into adulthood, and ideally life-long. Porous implants with similar stiffness to bone can promote bone ingrowth and thus beneficial clinical outcomes. A mechanical remodelling stimulus, strain energy density (SED), is thought to be the primary control variable of the process of bone growth into porous implants. The sequential process of bone growth needs to be taken into account to develop an accurate and validated bone remodelling algorithm, which can be employed to improve porous implant design and achieve better clinical outcomes. Methods. A bone remodelling algorithm was developed, incorporating the concept of bone connectivity (sequential growth of bone from existing bone) to make the algorithm more physiologically relevant. The algorithm includes adaptive elastic modulus based on apparent bone density, using a node-based model to simulate local remodelling variations while alleviating numerical checkerboard problems. Strain energy density (SED) incorporating stress and strain effects in all directions was used as the primary stimulus for bone remodelling. The simulations were developed to run in MATLAB interfacing with the commercial FEA software ABAQUS and Python. The algorithm was applied to predict bone ingrowth into a porous implant for comparison against data from a sheep model. Results. The accuracy of the predicted bone remodelling was verified for standard loading cases (bending, torsion) against analytical calculations. Good convergence was achieved. The algorithm predicted good bone remodelling and growth into the investigated porous implant. Using the standard algorithm without connectivity, bone started to remodel at locations unconnected to any bone, which is physiologically implausible. The implementation of bone connectivity ensures the gradual process of bone growth into the implant pores from the sides. The bone connectivity algorithm predicted that the full remodelling required more time (approximately 50% longer), which should be considered when developing post-surgical rehabilitation strategies for patients. Both algorithms with and without bone connectivity implementation converged to same final stiffness (less than 0.01% difference). Almost all nodes reached the same density value, with only a limited number of nodes (less than 1%) in transition areas with a strong density gradient having noticeable differences. Conclusions. An improved bone remodelling algorithm based on strain energy density that modelled the sequential process of bone growth has been developed and tested. For a porous metallic bone implant the same final bone density distribution as for the original adaptive elasticity theory was predicted, with a slower and more fidelic process of growth from existing surrounding bone into the porous implant. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Numerous papers present in-vivo knee kinematics data following total knee arthroplasty (TKA) from fluoroscopic testing. Comparing data is challenging given the large number of factors that potentially affect the reported kinematics. This paper aims at understanding the effect of following three different factors: implant geometry, performed activity and analysis method. A total of 30 patients who underwent TKA were included in this study. This group was subdivided in three equal groups: each group receiving a different type of posterior stabilized total knee prosthesis. During single-plane fluoroscopic analysis, each patient performed three activities: open chain flexion extension, closed chain squatting and chair-rising. The 2D fluoroscopic data were subsequently converted to 3D implant positions and used to evaluate the tibiofemoral contact points and landmark-based kinematic parameters. Significantly different anteroposterior translations and internal-external rotations were observed between the considered implants. In the lateral compartment, these differences only appeared after post-cam engagement. Comparing the activities, a significant more posterior position was observed for both the medial and lateral compartment in the closed chain activities during mid-flexion. A strong and significant correlation was found between the contact-points and landmarks-based analyses method. However, large individual variations were also observed, yielding a difference of up to 25% in anteroposterior position between both methods. In conclusion, all three evaluated factors significantly affect the obtained tibiofemoral kinematics. The individual implant design significantly affects the anteroposterior tibiofemoral position, internal-external rotation and timing of post-cam engagement. Both kinematics and post-cam engagement additionally depend on the activity investigated, with a more posterior position and associated higher patella lever arm for the closed chain activities. Attention should also be paid to the considered analysis method and associated kinematics definition: analyzing the tibiofemoral contact points potentially yields significantly different results compared to a landmark-based approach

Vertebral metastases are the most common type of malignant lesions of the spine. Although this tumour is still considered incurable and standard treatments are mainly palliative, the standard approach consists in surgical resection, which results in the formation of bone gaps. Hence, scaffolds, cements and/or implants are needed to fill the bone lacunae. Here, we propose a novel approach to address spinal metastases recurrence, based on the use of anti-tumour metallic-based nanostructured coatings. Moreover, for the first time, a gradient microfluidic approach is proposed for the screening of nanostructured coatings having anti-tumoral effect, to determine the optimal concentration of the metallic compound that permits selective toxicity towards tumoral cells. Coatings are based on Zinc as anti-tumour agent, which had been never explored before for treatment of bone metastases. The customized gradient generating microfluidic chip was designed by Autodesk Inventor and fabricated from a microstructured mould by using replica moulding technique. Microstructured mould were obtained by micro-milling technique. The chip is composed of a system of microfluidic channels generating a gradient of 6 concentrations of drug and a compartment with multiple arrays of cell culture chambers, one for each drug concentration. The device is suitable for dynamic cultures and in-chip biological assays. The formation of a gradient was validated using a methylene blue solution and the cell loading was successful. Preliminary biological data on 3D dynamic cultures of stromal cells (bone-marrow mesenchymal stem cells) and breast carcinoma cells (MDA-MB-231) were performed in a commercial microfluidic device. Results showed that Zn eluates had a selective cytotoxic effect for tumoral cells. Indeed, cell migration and cell replication of treated tumoral cells was inhibited. Moreover, the three-dimensionality of the model strongly affected the efficacy of Zn eluates, as 2D preliminary experiments showed a high cytotoxic effect of Zn also for stromal cells, thus confirming that traditional screening tests on 2D cultured cells usually lead to an overestimation of drug efficacy and toxicity. Based on preliminary data, the customized platform could be considered a major advancement in cancer drug screenings as it also allows the rapid and efficient screening of biomaterials having antitumor effect

Abstract. Objectives. Currently, total hip replacement surgery is an effective treatment for osteoarthritis, where the damaged hip joint is replaced with an artificial joint. Stress shielding is a mechanical phenomenon that refers to the reduction of bone density as a result of altered stresses acting on the host bone. Due to solid metallic nature and high stiffness of the current orthopaedic prostheses, surrounding bones undergo too much bone resorption secondary to stress shielding. With the use of 3D printing technology such as selective laser melting (SLM), it is now possible to produce porous graded microstructure hip stems to mimics the surrounding bone tissue properties. Method. In this study we have compared the physical and mechanical properties of two triply periodic minimal surface (TPMS) lattice structure namely gyroid and diamond TPMS. Based on initial investigations, it was decided to design, and 3D print the gyroid and diamond scaffolds having pore size of 800 and 1100 um respectively. Scaffold of each type of structure were manufactured and were tested mechanically in compression (n=8), tension (n=5) and bending (n=1). Results. Upon FEA validation of the scaffold in Abaqus, the desired scaffold for hip implant application was evaluated to have a young's modules of 12.15 GPa, yield strength of 242 MPa and porosity of 55%. Topology and lattice optimization were performed using nTopology to design an optimised graded porous hip implant based on stress shielding reduction. It was understood that the designed optimised hip implant can reduce the stress shielding effect by more than 65% when compared to the conventional generic implant. Conclusions. The designed hip implant presented in this work shows clinical promise in reducing bone loss while having enhanced osseointegration with the surrounding cortical bones. Hence, this will help reduce the risk of periprosthetic fracture and the probability of revision surgery

Bone tissue engineering is a promising strategy to treat the huge number of bone fractures caused by progressive population ageing and diseases i.e., osteoporosis. The bioactive and biomimetic materials design modulating cell behaviour can support healthy bone tissue regeneration. In this frame, type I collagen and hydroxyapatite (HA) have been often combined to produce biomimetic scaffolds. In addition, mesoporous bioactive glasses (MBGs) are known for their ability to promote the deposition of HA nanocrystals and their potential to incorporate and release therapeutic ions. Furthermore, the use of 3D printing technologies enables the effective design of scaffolds reproducing the natural bone architecture. This study aims to design biomimetic and bioactive 3D printed scaffolds that mimic healthy bone tissue natural features in terms of chemical composition, topography and biochemical cues. Optimised collagenous hybrid systems will be processed by means of extrusion 3D printing technologies to obtain high resolution bone-like structures. Protocols of human co-cultures of osteoblasts and osteoclasts will be developed and used to test the 3D scaffolds. Type I collagen has been combined with rod-like nano-HA and strontium containing MBGs (micro- and nano-sized particles) in order to obtain hybrid systems resembling the composition of native bone tissue. A comprehensive rheological study has been performed to investigate the potential use of the hybrid systems as biomaterial inks. Mesh-like structures have been obtained by means of extrusion-based technologies exploiting the freeform reversible embedding of suspended hydrogels (FRESH) approach. Different crosslinking methods have been tested to improve final constructs mechanical properties. Both crosslinked and non-crosslinked biomaterials were cultured with human osteoblasts and osteoclasts to assay the hybrid matrix biocompatibility as well as its influence on cell behaviour. Homogeneous hybrid systems have been successfully developed and characterised, proving their suitability as biomaterial inks for 3D printing technologies. Mesh-like structures have been extruded in a thermo-reversible gelatine slurry, exploiting the sol-gel transition of the systems under physiological conditions. Covalent bonds between collagen molecules have been promoted by genipin treatment, leading to a significant increase in matrix strength and stability. The collagen methacrylation and the further UV-crosslinking are under investigation as alternative promising method to reinforce the 3D structure during the printing process. Biological tests showed the potential of the developed systems especially for genipin treated samples, with a significant adhesion of primary cells. Collagenous hybrid systems proved their suitability for bioactive 3D printed structures design for bone tissue engineering. The multiple stimuli provided by the scaffold composition and structure will be investigated on both direct and indirect human osteoblasts and osteoclasts co-culture, according to the developed protocols

Abstract. Background. The Oxford Domed Lateral (ODL) Unicompartmental Knee Replacement (UKR) has some advantages over other lateral UKRs, but the mobile bearing dislocation rate is high (1–6%). Medial dislocations, with the bearing lodged on the tibial component wall, are most common. Anterior/posterior dislocations are rare. For a dislocation to occur distraction of the joint is required. We have developed and validated a dislocation analysis tool based on a computer model of the ODL with a robotics path-planning algorithm to determine the Vertical Distraction required for a Dislocation (VDD), which is inversely related to the risk of dislocation. Objectives. To modify the ODL design so the risk of medial dislocation decreases to that of an anterior/posterior dislocation. Methods. The components were modified using Solidworks. For each modification the dislocation analysis tool was used to determine the VDD for medial dislocation (with bearing 0–6mm from the tibial wall). This was compared with the original implant to identify the modifications that were most effective at reducing the dislocation risk. These modifications were combined into a final design, which was assessed. Results. Modifying the tibial component plateau, changing the femoral component width and making the bearing wider medially had little effect on VDD. Shifting the femoral sphere centre medially decreased VDD. Shifting the femoral sphere laterally, increasing tibial wall height and increasing bearing width laterally increased VDD. A modified implant with a femoral sphere centre 3mm lateral, wall 2.8mm higher, and bearing 2mm wider laterally, implanted so the bearing is ≤4mm from the tibial wall with a bearing thickness ≥4mm had a minimum VDD for medial dislocation of 5.75mm, which is larger than the minimum VDD for anterior/posterior dislocation of 5.5mm. Conclusions. A modified ODL design should decrease the dislocation rate to an acceptable level, however, further testing in cadavers is required. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Introduction and Objective. Kinematic Alignment (KA) is a surgical technique that restores the native knee alignment following Total Knee Arthroplasty (TKA). The association of this technique with a medial pivot implant design (MP) attempts to reestablish the physiological kinematics of the knee. Aim of this study is to analyze the clinical and radiological outcomes of patients undergoing MP-TKA with kinematic alignment, and to assess the effect of the limb alignment and the orientation of the tibial component on the clinical outcomes. Materials and Methods. We retrospectively analyzed 63 patients who underwent kinematic aligned medial pivot TKA from September 2018 to January 2020. Patient-Related Outcomes (PROMs) and radiological measures were collected at baseline, 3 months and 12 months after surgery. Results. We demonstrated a significant improvement in the clinical and functional outcomes starting from 3 months after surgery. This finding was also confirmed at the longest follow-up. The clinical improvement was independent from the limb alignment and from the orientation of the tibial component. The radiological analysis showed that the patient's native limb alignment was restored, and that the joint line orientation maintained the parallelism to the floor when standing. This latter result has a particular relevance, as it may positively influence the outcomes, reducing the risk of wear and mobilization of the implant. Conclusions. The association of kinematic alignment and a medial pivot TKA implant allows for a fast recovery, good clinical and functional outcomes, independently from the final limb alignment and the tibial component orientation

Biomimicry is defined as the design and production of materials, structures, and systems that are modelled on biological entities and processes. Within the medical device sector, biomimicry uses an ecological standard to judge the “rightness” of biomaterial components and devices. After 3.8 billion years of evolution, nature has learned what works, what is appropriate, and what lasts. Biomimicry is a new way of viewing and valuing nature, and it introduces an era based not on what we can extract from the natural world, but on what we can learn from it. Original design manufacturing biomaterial projects that leverage the practice of biomimicry will be discussed. Both natural and synthetic polymer platforms will be reviewed for soft tissue and hard tissue applications. Given the complexity of musculoskeletal tissue structures, the key challenge is identifying the most appropriate materials and forms for recapitulating the native function in a tissue scaffold design. The general field of biomimicry will be reviewed along with specific examples in the regenerative medicine sector

Physiological kinematics is very difficult to restore after total knee arthroplasty (TKA). A new model of medial stabilized (MS) TKA prosthesis has a high spherical congruence of the internal compartment, which guarantees anteroposterior (AP) stability associated with a flat surface of the insert in the lateral compartment, that allows a greater AP translation of the external condyle during knee flexion. The aim of our study is to evaluate, by dynamic radiostereometric analysis (RSA), the knee in vivo kinematics after the implantation of a MS prosthesis during sit to stand and lunge movements. To describe the in vivo kinematics of the knee after MS Fixed Bearing TKA (GMK Sphere (TM) Medacta International AG, Castel San Pietro, Switzerland) using Model Based dynamic RSA. A cohort of 18 patients (72.1 ± 7.4 years old) was evaluated by dynamic RSA 9 months after TKA. The kinematic evaluation was carried out using the dynamic RSA tool (BI-STAND DRX 2), developed at our Institute, during the execution of sit to stand and lunge movements. The kinematic data were processed using the Grood and Suntay decomposition and the Low Point method. The patients performed two motor tasks: a sit-to-stand and a lunge. Data were related to the flexion angle versus internal-external, varus-valgus rotations and antero-posterior translations of the femur with respect to the tibia. During the sit to stand, the kinematic analysis showed the presence of a medial pivot, with a significantly greater (p=0.0216) anterior translation of the lateral condyle (3.9 ± 0.8 mm) than the medial one (1.6 ± 0.8 mm) associated with a femoral internal rotation (4.5 ± 0.9 deg). During the lunge, in the flexion phase, the lateral condyle showed a larger posterior translation than the medial one (6.2 ± 0.8 mm vs 5.3 ± 0.8 mm) associated with a femoral external rotation (3.1 ± 0.9 deg). In the extension phase, there is a larger anterior translation of the lateral condyle than the medial one (5.8 ± 0.8 mm vs 4.6 ± 0.8 mm) associated with femoral internal rotation (6.2 ± 0.9 deg). Analysing individual kinematics, we also found a negative correlation between clinical scores and VV laxity during sit to stand (R= −0.61) and that the higher femoral extra-rotation, the poorer clinical scores (R= 0.65). The finding of outliers in the VV and IE rotations analysis highlights the importance of a correct soft tissue balancing in order to allow the prosthetic design to manifest its innovative features

Background and aim. Recent proposals have been introduced to modify stem design and/or femoral fixation in total hip replacement (THR). New designs need to consider previous design features and their results. The aim of this study has been to evaluate the clinical and radiological results of six different designs of tapered uncemented stems implanted in our Institution. Methods. 1918 uncemented hips were prospectively assessed from 1999 to 2011 (minimum follow-up of five years for the unrevised hips). All hips had a 28 or 32 mm femoral head and metal-on-polyethylene or alumina-on-alumina bearing surface. Six uncemented femoral designs that shared a femoral tapered stem incorporating a coating surface were included in the study. The different design features included the type of coating, metaphyseal filling, and sectional shape. Results. Intra-operative proximal femoral crack was 6.7% in one of the designs (p=0.01), univariate analysis showing a lower risk of crack in the other designs. The position of the stem was neutral in 80% of the cases for all designs. Femoral canal filing was related to the stem design (p<0.001 at the three levels) and to the femoral level assessed (subset alpha=0.005). Twelve stems were revised for aseptic loosening (6 from two different designs). The survival rate for femoral aseptic loosening at 15 years was 96.6% (95% CI 93.8 to 99.4) for one of these two designs ad 97.4% (95% CI95.5 to 99.6) for the other. Regression analysis showed that stem design was the only factor related to aseptic loosening when adjusted for femoral canal filling (at the three levels) stem position (neutral or not) and femoral type (cylindrical or not). Conclusion. Tapered uncemented stems consistently provide excellent bone fixation. New designs need to avoid changing successful features and concentrate on the less successful aspects

The successful application of smart implantable devices requires materials used to easily adapt and respond to their microenvironment via physical and chemical cues. Nanotopography, a known important factor in cellular processes (i.e. cellular adhesion, proliferation, and, differentiation), has become a central approach to imparting clinically relevant materials with bioactive and biomimetic properties. This work focuses on the use of Directed irradiation synthesis (DIS), to create nanostructures on dissimilar materials including surfaces of metals, semiconductors, and polymers. DIS is a novel method that allows for the tuning of both surface nanoscale topography and surface chemistry through the tailoring of ion beam parameters, including energy and fluence. The application of DIS to direct cellular interactions on Ti6Al4V, MgAZ31, and PEEK is presented. Topography and chemistry changes at the nanoscale were characterized by SEM, XPS, AFM, and Contact Angle. In vitro tests were performed using macrophages (JJ741A) and human aortic and bone marrow mesenchymal stem cell (MSCs). DIS promotes an advanced cell adhesion state where cells are orientated following the designed nanofeatures in all irradiated specimens. A delay on immune response due to low levels of TNFa and higher levels of IL10 on irradiated Ti6Al4V were observed. Modified PEEK showed 3-fold higher ALP content at 7 days compared to pristine samples, and porous MgAZ31 treated with DIS revealed lower corrosion state and increased cell proliferation of HBMMSCs. Controlling the nanopatterning in biomaterials using DIS enables the design of bioactive surfaces to highly promote implant integration and tissue regeneration

Introduction

Current treatments of rotational deformities of long bones in children are osteotomies and fixations.

In recent years, the use of guided growth for correction of rotational deformities has been reported in several pre-clinical and clinical studies. Various techniques have been used, and different adverse effects, like growth retardation and articular deformities, have been reported. We tested a novel plate concept intended for correction of rotational deformities of long bones by guided growth, with sliding screw holes to allow for longitudinal growth, in a porcine model.

Device-associated infection remains a serious clinical problem in orthopaedic and trauma surgery. The emergence of resistant organisms such as methicillin resistant Staphylococcus aureus (MRSA) has further exacerbated this problem by limiting the range of treatment options. Currently, systemic antibiotic therapy is the cornerstone of treatment, alongside surgical resection of infected tissues and implant removal. The potential for antibiotic loaded biomaterials to support the prevention and treatment of infection is significant, although the currently available options are limited in number and often re-purposed from other applications e.g. antibiotic loading of bone cement. The first part of the talk will cover the basic concepts involved in antibiotic treatment, with an emphasis on the ideal antibiotic release kinetics from biomaterials, and how bacterial biofilms and antibiotic resistance influence antimicrobial efficacy. The next generation of biomaterials for antibiotic delivery should be specifically designed with this knowledge in mind. Regulatory approval of antimicrobial combination devices, however, is an evolving process as regulatory bodies seek more robust and clinically relevant efficacy data. Approval will require preclinical efficacy using standardized animal models that recapitulate the key features of the clinical disease. The second part of this talk will cover best practice in this important stage of development

Summary Statement. Reverse shoulder design philosophy can impact external rotation moment arms. Lateralizing the humerus can increase the external rotator moment arms relative to normal anatomy. Introduction. The design of reverse shoulders continues to evolve. These devices are unique in that they are not meant to reproduce the healthy anatomy. The reversal of the fulcurm in these devices impacts every muscle that surrounds the joint. This study is focused on analyzing the moment arms for the rotator cuff muscles involved in internal and external rotation for a number of reverse shoulder design philosophies. Methods. Four of the most common design philosophies were chosen. The first, a Grammont style prosthesis, with a center of rotation (COR) on the glenoid face and a humeral cup countersunk into the proximal humerus (MGMH). The second concept is the MGMH design lateralised by a 10mm bone graft (BIO). The third concept has a lateralised glenosphere COR and a humeral component inside the proximal humerus (LGMH). The fourth design has a medialised COR with a humeral component placed on top of the humerus (MGLH). This places the humerus further lateral than the previous designs. For each component set, a representative implant was modeled based on published specifications. Each design was implanted into the same digital bone models (consisting of a humerus, scapula, clavicle, and ribcage) following the manufacturer's recommended surgical technique. The muscles analyzed were the posterior-deltoid (PD), subscapularis (SSC), infraspinatus (IS), and teres minor (TM). These muscles were allowed to wrap around the bone of the scapula and proximal humerus through the range of motion. All muscle origin and insertion points were kept constant throughout the analysis. The assemblies were externally rotated from an initial position of 45° internal rotation to 45° of external rotation of the humerus with the arm at 0° of abduction. The moment arms for all muscles were compared to those calculated for the anatomic shoulder. Results. All the rotator cuff muscles displayed a similar trend with the reverse shoulder. The external rotators all had similar moment arm values at neutral (IS∼22mm, TM∼20mm), but increased at rates proportional to their humeral offsets with external rotation (IS-MGLH 32.3mm, LGMH 27.5mm, MGMH and BIO 26.25mm; TM-MGLH 31.3mm, LGMH 27.8mm, MGMH and BIO 26.5mm). The SSC internal rotation moment arm remains roughly constant at 20mm for the anatomic shoulder, but varies widely from 45° external to 45° internal rotation with the different designs (MGLH 31.4mm to 6.7mm; MGMH 25.1mm to 11.2mm; LGMH 26.2mm to 10.8mm; BIO 25.4mm to 4.8mm). The PD moment arm is increased relative to the anatomic shoulder during external rotation for the MGLH design (9.3mm vs. 7.4mm). The other designs exhibit a decrease in the moment arm of this muscle relative to the anatomic design (LGMH 7.3mm, MGMH 5.8mm, BIO 6.4mm). Discussion. The lateral offset between the center of humeral axis and the muscle insertion on the humerus dominates the external rotation moment arm value through this range of motion. This is evident by the increase in the moment arms with external rotation for the different reverse shoulder designs. The increase in external rotation efficiency for the external rotators and PD could play a critical role in post-operative external rotation strength and motion

Introduction. Modern forearm crutches have evolved little since their invention last century. We evaluated comfort and user satisfaction of 2 spring-loaded crutches compared with existing crutch designs. Methods. 25 healthy subjects (11 male, average age 26.2 years; 14 female, average age 22.7 years) participated. Each used 5 different crutches in a randomly allocated order:. standard forearm crutch (ergonomic grip);. spring-loaded crutch (soft spring, ergonomic grip);. spring-loaded crutch (firm spring, ergonomic grip);. standard forearm crutch (normal grip);. axillary crutch. Participants completed a purpose built course at the Pedestrian Accessibility and Movement LAboratory, UCL (PAMELA). The course consisted of a mixture of slopes (transverse and longitudinal), sprint, slalom, and a slow straight. All participants completed questionnaires relating to crutch user preference and design features. Results. Crutches were ranked in order of preference. The crutch least favoured was the axillary design, irrespective of subject weight, followed by the standard forearm crutch with normal grip. The 3 crutches with ergonomic handles all scored similarly. Preferences were also analysed in two weight controlled groups and compared against the soft and firm spring-loaded crutches. Of the lighter group 80% preferred the softer spring. Of the heavier group 56% preferred the firmer spring. Over 50% of subjects rated handle/cuff comfort as a key feature in crutch design. Conclusions. Preference for different spring tensions depended on subject weight, which should be the focus of further research. The least favoured crutches were the axillary and standard issue forearm grip crutch. Comfort was the most important feature in crutch design with preference for ergonomic handles, followed by cuff design ranked the most important. Spring-loaded crutches performed comparably to the other crutches with ergonomic handles

First works focuses on the characterization (physical and biological) of this biomaterial. Current work had studied osteoinductive and osteoconductive capacity of these hydrogels. In vivoresults highlight a significant bone reconstruction two months after implantations on bone lesions in mice. Bone is a dynamic and vascularized tissue that has the ability of naturally healing upon damage. Nevertheless, in the case of critical size defects this potential is impaired. Present approaches mainly consider autografts and allografts, which presents several limitations. Bone Tissue Engineering (BTE) is based on the use of 3D matrices to guide both cellular growth, differentiation to promote bone regeneration. Hence, matrices can contain biological materials such as cells and growth factors. Our project aims to design a hydrogel for BTE, particularly for bone lesion filling. We previously showed that a porous 3D hydrogel, Glycosyl-Nucleoside-Fluorinated (GNF) is: 1) non-cytotoxic to clustered human Adipose Mesenchymal Stem Cells (hASCs), 2) bioinjectable and 3) biodegradable. Therefore, this novel class of hydrogels show promise for the development of therapeutic solutions for BTE [1]. The hypothesis of this research was that improving the capacity to promote the adhesion of cells by adding collagen gel matrices and bone morphogenic protein 2 (BMP-2) to improve the bone regenerative potential of this gel. Collagen is a protein matrix well known for its cytocompatibility [2]. BMP-2, have been shown ability to induce bone formation in combination with an adequate matrix [3]. Thereby, the overall aim of this work was to design, develop and validate a new composite hydrogel for BTE. GNF was prepared as previously described in detail[1], at a concentration of 3% (w/v). Type I-collagen gel was prepared from rat-tail tendons at a concentration of 4 g/L [2]. hASCs were isolated from human adipose tissue in our laboratory. To establish a suitable microenvironment for cell proliferation and differentiation cells were seeded in collagen and then GNF gel was added and the resulting mixture was blended, BMP-2 (InductOs ® Kit) is added to this preparation (5µm BMP-2/ml). Fluorometry was used to follow BMP2 release in vitro andin vivo(NOG mices;n=6), orthotopic calvariumbone critical defect (3.3 mm) has been selected to challenge the bone repair. Adding collagen hydrogel improve cell adhesion, survivals and proliferation rather than simple GNF hydrogel. This novel gel composite has the ability to sustain hASCs adhesion and differentiation towards the osteoblastic lineage (positive ALP cells). Fluorometry showed the ability of our hydrogel to prolong the residence of BMP-2 (in vitro and in vivo) compared to collagen hydrogel sponges. Implantation of hydrogel containing hASC and BMP-2 has shown encouraging results in bone reconstruction: 2 months after implantation of biomaterials a significant bone reconstruction can be observed using X-Ray imaging. Adding collagen to GNF allowed to obtain gels showing satisfactory cell-behaviour. In parallel, the presence of GNF hydrogel helps to improve mechanical properties of the biomaterial (hydrogel stability and controlled release of BMP-2). The first in vivostudies have shown encouraging bone regeneration capacity of these hydrogels. The implantation performed on a larger number of animals and quantitative microCT analysis will enable us to judge the effectiveness of this hydrogel as a new injectable biomaterial for BTE. This work was partially supported by NSERC-Canada, FRQ-NT-Quebec, FRQ-S- Quebec, and CFI-Canada. Mathieu Maisani was awarded of a NSERC CREATE Program in Regenerative Medicine (www.ncprm.ulaval.ca)