Cells typically respond to a variety of geometrical cues in their environment, ranging from nanoscale surface topography to mesoscale surface curvature. The ability to control cellular organisation and fate by engineering the shape of the extracellular milieu offers exciting opportunities within tissue engineering. Despite great progress, however, many questions regarding geometry-driven tissue growth remain unanswered. Here, we combine mathematical surface design, high-resolution microfabrication, in vitro cell culture, and image-based characterization to study spatiotemporal cell patterning and bone tissue formation in geometrically complex environments. Using concepts from differential geometry, we rationally designed a library of complex mesostructured substrates (10. 1. -10. 3. µm). These substrates were accurately fabricated using a combination of two-photon polymerisation and replica moulding, followed by surface functionalisation. Subsequently, different cell types (preosteoblasts, fibroblasts, mesenchymal stromal cells) were cultured on the substrates for varying times and under varying osteogenic conditions. Using imaging-based methods, such as fluorescent confocal microscopy and second harmonic generation imaging, as well as quantitative image processing, we were able to study early-stage spatiotemporal cell patterning and late-stage extracellular matrix organisation. Our results demonstrate clear geometry-dependent cell patterning, with cells generally avoiding convex regions in favour of concave domains. Moreover, the formation of multicellular bridges and collective curvature-dependent cell orientation could be observed. At longer time points, we found clear and robust geometry-driven orientation of the collagenous extracellular matrix, which became apparent with second harmonic generation imaging after ∼2 weeks of culture. Our results highlight a key role for geometry as a cue to guide spatiotemporal cell and tissue organisation, which is relevant for scaffold design in tissue engineering applications. Our ongoing work aims at understanding the underlying principles of geometry-driven tissue growth, with a focus on the interactions between substrate geometry and mechanical forces

Osteoporosis is a progressive, chronic disease of bone metabolism, characterized by decreased bone mass and mineral density, predisposing individuals to an increased risk of fractures. The use of animal models, which is the gold standard for the screening of anti-osteoporosis drugs, raises numerous ethical concerns and is highly debated because the composition and structure of animal bones is very different from human bones. In addition, there is currently a poor translation of pre-clinical efficacy in animal models to human trials, meaning that there is a need for an alternative method of screening and evaluating new therapeutics for metabolic bone disorders, in vitro. The aim of this project is to develop a 3D Bone-On-A-Chip that summarizes the spatial orientation and mutual influences of the key cellular components of bone tissue, in a citrate and hydroxyapatite-enriched 3D matrix, acting as a 3D model of osteoporosis. To this purpose, a polydimethylsiloxane microfluidic device was developed by CAD modelling, stereolithography and replica molding. The device is composed by two layers: (i) a bottom layer for a 3D culture of osteocytes embedded in an osteomimetic collagen-enriched matrigel matrix with citrate-doped hydroxyapatite nanocrystals, and (ii) a upper layer for a 2D perfused co-culture of osteoblasts and osteoclasts seeded on a microporous PET membrane. Cell vitality was evaluated via live/dead assay. Bone deposition and bone resorption was analysed respectively with ALP, Alizarin RED and TRACP staining. Osteocytes dendrite expression was evaluated via immunofluorescence. Subsequently, the model was validated as drug screening platform inducing osteocytes apoptosis and administrating standard anti-osteoporotic drugs. This device has the potential to substitute or minimize animal models in pre-clinical studies of osteoporosis, contributing to pave the way for a more precise and punctual personalized treatment

While the COVID-19 pandemic highlighted the need for more accessible anatomy instruction tools, it is also well known that the time allocated to practical anatomy teaching has reduced in the past decades. Notably, the opportunity for anatomy students to learn osteology is not prioritised, nor is the ability of students to appreciate osteological variation. As a potential method of increasing accessibility to bone models, this study describes the process of developing 3D-printed replicas of human bones using a combination of structured light scanning (SLS) technology and 3D printing. Human bones were obtained from the Anatomy Lab at the University of Edinburgh and were digitised using SLS via an Einscan H scanner. The resulting data was then used to print multiple replicas of varying materials, colours, scales and resolutions on an Ultimaker S3 3D printer. To gather opinion on these models and their variables, surveys were completed by anatomy students and educators (n=57). Data was collected using a Likert scale response, as well as free-text answers to gather qualitative information. 3D scans of the scapula, atlas (C1 vertebrae) and femur were successfully obtained. Plastic replicas were produced with defined variables in 4 separate stations e.g. different colours, to obtain results from survey respondents. For colour, 87.7% of survey respondents preferred white models, with 7% preferring orange and 5.3% preferring blue. For material, 47.4% of respondents preferred PLA (Polylactic acid), while 33.3% preferred ABS (Acrylonitrile butadiene styrene), 12.3% preferred Pet-G (Polyethylene terephthalate glycol), 3.5% preferred Glassbend and 3.5% had no preference. Additional results based on scale and resolution were also collected. This initial study has demonstrated a proof-of-concept workflow for SLS technology to be combined with 3D printing to produce plastic replicas of human bones. Our study has provided key information about the colour, scale, material and resolution required for these models. Our future work will focus on determining accuracy of the models and their use as teaching aids for osteology education

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

In the last years, 3d printing has progressively grown and it has reached a solid role in clinical practice. The main applications brought by 3d printing in orthopedic surgery are: preoperative planning, custom-made surgical guides, custom-made im- plants, surgical simulation, and bioprinting. The replica of the patient's anatomy, starting from the elaboration of medical volumetric images (CT, MRI, etc.), allows a progressive extremization of treatment personalization that could be tailored for every single patient. In complex cases, the generation of a 3d model of the patient's anatomy allows the surgeons to better understand the case — they can almost “touch the anatomy” —, to perform a more ac- curate preoperative planning and, in some cases, to perform device positioning before going to the surgical room (i.e. joint arthroplasty). 3d printing is also commonly used to produce surgical cutting guides, these guides are positioned intraoperatively on given landmarks to guide the surgeon to perform a specific surgical act (bone osteotomy, bone resection, implant position, etc.). In total knee arthroplasty, custom-made cutting guides have been developed to help the surgeon align the femoral and tibial components to the pre-arthritic condition with- out the use of the intramedullary femoral guide. 3d printed custom-made implants represent an emerging alternative to biological reconstructions especially after oncologic resection surgery or in case of complex arthroplasty revision surgery. Custom-made implants are designed to re- place the original shape and size of the patient's bone and they allow an extreme personalization of the treatment for every single patient. Patient-specific surgical simulation is a new frontier that promises great benefits for surgical training. a solid 3d model of the patient's anatomy can faithfully reproduce the surgical complexity of the patient and it allows to generate surgical simulators with increasing difficulty to adapt the difficulties of the course with the level of the trainees performing structured training paths: from the “simple” case to the “complex” case

Aims

To compare the cost-utility of standard dressing with incisional negative-pressure wound therapy (iNPWT) in adults with closed surgical wounds associated with major trauma to the lower limbs.

Aims

We compared implant and patient survival following intraoperative periprosthetic femoral fractures (IOPFFs) during primary total hip arthroplasty (THA) with matched controls.

Aims

The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model.

Increasing innovation in rapid prototyping (RP) and additive manufacturing (AM), also known as 3D printing, is bringing about major changes in translational surgical research.

This review describes the current position in the use of additive manufacturing in orthopaedic surgery.

Cite this article: Bone Joint J 2018;100-B:455-60.

Objectives

Taper junctions between modular hip arthroplasty femoral heads and stems fail by wear or corrosion which can be caused by relative motion at their interface. Increasing the assembly force can reduce relative motion and corrosion but may also damage surrounding tissues. The purpose of this study was to determine the effects of increasing the impaction energy and the stiffness of the impactor tool on the stability of the taper junction and on the forces transmitted through the patient’s surrounding tissues.

Total knee arthroplasty (TKA) is widely accepted as a successful surgical intervention to treat osteoarthritis and other degenerative diseases of the knee. However, present statistics on limited survivorship and patient-satisfaction emphasise the need for an optimal endoprosthetic care. Although, the implant design is directly associated with the clinical outcome comprehensive knowledge on the complex relationship between implant design (morphology) and function is still lacking. The goal of this study was to experimentally analyse the relationship between the trochlear groove design of the femoral component (iTotal CR, ConforMIS, Inc., Bedford, MA, USA) and kinematics in an in vitro test setup based on rapid prototyping of polymer-based replica knee implants. The orientation of the trochlear groove was modified in five different variations in a self-developed computational framework. On the basis of the reference design, one was medially tilted (−2°) and four were laterally tilted (+2°, +4°, +6°, +8°). For manufacturing, we used rapid prototyping to produce synthetic replicates made of Acrylnitril-Butadien-Styrol (ABS) and subsequent post-processing with acetone vapor. The morpho-functional analysis of the replicates was performed in our experimental knee simulator. Tibiofemoral and patellofemoral kinematics were recorded with an optical tracking system during a semi-active flexion/extension (∼10° to 90°) motion. Looking at the results, the patellofemoral kinematics, especially the medial/lateral translation and internal/external rotation were mainly affected. During low flexion, the patella had a more laterally position relative to the femur with increasing lateral trochlear orientation. The internal/external rotation initially differentiated and converged with flexion. Regarding the tibiofemoral kinematics, only the tibial internal/external rotation showed notable differences between the modified replica implants. We presented a workflow for an experimental morpho-functional analysis of the knee and demonstrated its feasibility on the example of the trochlear groove orientation which might be used in the future for comprehensive implant design parameter optimisation, especially in terms of image based computer assisted patient-specific implants

Aims

Recently, there has been considerable interest in quantifying the associations between bony abnormalities around and in the hip joint and osteoarthritis (OA). Our aim was to investigate the relationships between acetabular undercoverage, acetabular overcoverage, and femoroacetabular impingement (FAI) with OA of the hip, which currently remain controversial.

Objectives

External fixators are the traditional fixation method of choice for contaminated open fractures. However, patient acceptance is low due to the high profile and therefore physical burden of the constructs. An externalised locking compression plate is a low profile alternative. However, the biomechanical differences have not been assessed. The objective of this study was to evaluate the axial and torsional stiffness of the externalised titanium locking compression plate (ET-LCP), the externalised stainless steel locking compression plate (ESS-LCP) and the unilateral external fixator (UEF).

INTRODUCTION. Most total knees today are CR or PS, with lateral and medial condyles similar in shape. There is excellent durability, but a shortfall in functional outcomes compared with normals, evidenced by abnormal contact points and gait kinematics, and paradoxical sliding. However unicondylar, medial pivot, or bicruciate retaining, are preferred by patients, ascribed to AP stability or retention of anatomic structures (Pritchett; Zuiderbaan). Recently, Guided Motion knees have been shown to more closely reproduce anatomic kinematics (Walker; Willing; Amiri; Lin; Zumbrunn). As a design approach we proposed Design Criteria: reproduce the function of each anatomic stabilizing structure with bearing surfaces on the lateral and medial sides and intercondylar; resected cruciates because this is surgically preferred; avoid a cam-post because of central femur bone removal, soft tissue entrapment, noises, and damage (Pritchett; Nunley). Our hypothesis was that these criteria could produce a Guided Motion design with normal kinematics. METHODS & MATERIALS. Numerous studies on stability and laxity showed the ACL was essential to controlling posterior femoral displacement on the tibia whether the knee was loaded or unloaded. Under load, the anterior upwards slope of the medial tibial plateau prevented anterior displacement (Griffen; Freeman; Pinskerova; Reynolds). The posterior cruciate and the downward lateral tibial slope produced lateral rollback in flexion. The Replica Guided Motion knee had 3 bearings (Fig 1). The lateral side was shallow and sloped posteriorly, with a posterior lip to prevent excess displacement. The medial anterior tibial and femoral slopes were increased as in the anatomic knee. In the intercondylar region, a saddle bearing replaced ACL function by controlling posterior femoral displacement. For testing, a typical PS design was used as comparison. A Knee Test Machine (Fig 2) flexed the knee, and applied axial compression, shear and torque to represent a range of functions. Bone shapes were reproduced by 3D printing and collaterals by elastomeric bands. Motion was recorded with a digital camera, and Geomagic to process data. RESULTS. The kinematics of normal knees was the benchmark (Arno). The results for neutral path of motion, and the AP laxity about the neutral path, are shown (Fig 3). The PS showed symmetric motion, with anterior medial sliding and excessive constraint in low and high flexion. For the Replica, the medial condyle remained almost constant, but the lateral side rolled posteriorly with flexion, less than normal to prevent damage to the posterior lateral tibial plastic. The lateral side had similar anterior laxity to anatomic, but more than anatomic in late flexion. Based on 10 parameter motion scoring, the Replica was closer to normal than the PS, 82% cf 51%. DISCUSSION. Functional outcomes after TKA are less than normal, TKA design being a likely factor. The approach shown here is intended to reproduce more anatomic kinematics of neutral path of motion and laxity. Such a Replica Guided Motion knee, based on an anatomic structure/stability approach, could reproduce close to normal kinematics even without the cruciates or a cam-post. This may result in improved functional outcomes, and a closer feeling of a normal knee. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Background. Total Ankle Replacement (TAR) has become a common surgical procedure for severe Osteoarthritis of the ankle. Unlike hip and knee, current TARs still suffer from high failure rates. A key reason could be their non-anatomical surface geometry design, which may produce unnatural motion and load-transfer characteristics. Current TARs have articular surfaces that are either cylindrical or truncated cone surfaces following the Inman truncated cone concept from more than 60 years ago [1]. Our recent study demonstrated, that the surfaces of the ankle can be approximated by a Saddle-shaped, Skewed, truncated Cone with its apex directed Laterally (SSCL) [2]. This is significantly different than the surface geometry used in current TAR systems. The goal of this study was to develop and test the reliability of an in vitro procedure to investigate the effect of different joint surface morphologies on the kinematics of the ankle and to use it to compare the effect of different joint surface morphologies on the 3D kinematics of the ankle complex. Methodology. The study was conducted on ten cadaver ankle specimens. Image processing software (Analyze Direct. TM. ) was used to obtain 3D renderings of the articulating bones. The 3D bone models were then introduced into engineering design software packages (, Geomagic. TM. and Inventor. TM. ) to produce a set of four custom-fit virtual articular surfaces for each specimen: 1. Exact replica of the natural surfaces; 2. cylindrical; 3. truncated cone with apex oriented medially according to Inman's postulate; and 4. SSCL. The virtual TAR implants were exported to a 3D printing software and 3D physical models of each implant was produced in PLA using 3D printing (Figure 1). The intact cadaver was tested first in a specially design loading and measuring system [3] in which external moments were applied across the ankle in the three planes of motion and the resulting motion was measured through a surgical navigation system (Figure 1). Each of the four customized implant sets were then surgically introduced one at a time and the test was repeated. From the results, the ankle, subtalar and complex kinematics could be compared to that of the intact natural joint. Results and Conclusions. 1. Replacing the natural ankle joint surfaces by artificial exact replicas do not significantly affect the kinematic characteristics thus establishing good reliability of the experimental technique. This high reliability is an important finding proving that the combined factors involved in the process, such as replacing the natural surfaces with artificial replicas and the overall surgical procedure, do not significantly affect the kinematic characteristics of the ankle joint; 2. The SSCL implant produces close to intact joint kinematics (Figure 3), 3. The SSCL produces closer to normal kinematics then TARs with either cylindrical surfaces or those representing a symmetric truncated cone with apex oriented medially (Figure 3). For any figures or tables, please contact authors directly (see Info & Metrics tab above).

To determine the mechanisms and extents of popliteus impingements before and after TKA and to investigate the influence of implant sizing. The hypotheses were that (i) popliteus impingements after TKA may occur at both the tibia and the femur and (ii) even with an apparently well-sized prosthesis, popliteal tracking during knee flexion is modified compared to the preoperative situation. The location of the popliteus in three cadaver knees was measured using computed tomography (CT), before and after implantation of plastic TKA replicas, by injecting the tendon with radiopaque liquid. The pre- and post-operative positions of the popliteus were compared from full extension to deep flexion using normosized, oversized and undersized implants (one size increments). At the tibia, TKA caused the popliteus to translate posteriorly, mostly in full extension: 4.1mm for normosized implants, and 15.8mm with oversized implants, but no translations were observed when using undersized implants. At the femur, TKA caused the popliteus to translate laterally at deeper flexion angles, peaking between 80º-120º: 2.0 mm for normosized implants and 2.6 mm with oversized implants. Three-dimensional analysis revealed prosthetic overhang at the postero-superior corner of normosized and oversized femoral components (respectively, up to 2.9 mm and 6.6 mm). A well-sized tibial component modifies popliteal tracking, while an undersized tibial component maintains more physiologic patterns. Oversizing shifts the popliteus considerably throughout the full arc of motion. This study suggests that both femoro- and tibio-popliteus impingements could play a role in residual pain and stiffness after TKA

A large number of total hip arthroplasties (THA) are performed each year, of which 60 % use cementless femoral fixation. This means that the implant is press-fitted in the bone by hammer blows. The initial fixation is one of the most important factors for a long lasting fixation [Gheduzzi 2007]. It is not easy to obtain the point of optimal initial fixation, because excessively press-fitting the implant by the hammer blows can cause peak stresses resulting in femoral fracture. In order to reduce these peak stresses during reaming, IMT Integral Medizintechnik (Luzern, Switzerland) designed the Woodpecker, a pneumatic reaming device using a vibrating tool. This study explores the feasibility of using this Woodpecker for implant insertion and detection of optimal fixation by analyzing the vibrational response of the implant and Woodpecker. The press-fit of the implant is quantified by measuring the strain in the cortical bone surrounding the implant. An in vitro study is presented. Two replica femur models (Sawbones Europe AB, Malmo Sweden) were used in this study. One of the femur models was instrumented with three rectangular strain gauge rosettes (Micro-Measurements, Raleigh, USA). The rosettes were placed medially, posteriorly and anteriorly on the proximal femur. Five paired implant insertions were performed on both bone models, alternating between standard hammer blow insertions and using the Woodpecker. The vibrational response was measured during the insertion process, at the implant and Woodpecker side using two shock accelerometers (PCB Piezotronics, Depew, NY, USA). The endpoint of insertion was defined as the point when the static strain stopped increasing. Significant trends were observed in the bandpower feature that was calculated from the vibrational spectrum at the implant side during the Woodpecker insertion. The bandpower is defined as the percentage power of the spectrum in the band 0–1000 Hz. Peak stress values calculated from the strain measurement during the insertion showed to be significantly (p < 0.05) lower at two locations using the Woodpecker compared to the hammer blows at the same level of static strain. However, the final static strain at the endpoint of insertion was approximately a factor two lower using the Woodpecker compared to the hammer. A decreasing trend was observed in the bandpower feature, followed by a stagnation. This point of stagnation was correlated with the stagnation of the periprosthetic stress in the bone measured by the strain gages. The behavior of this bandpower feature shows the possibility of using vibrational measurements during insertion to assess the endpoint of insertion. However it needs to be taken into account that it was not possible to reach the same level of static strain using the Woodpecker as with the hammer insertion. This could mean that either extra hammer blows or a more powerful pneumatic device could be needed for proper implant insertion

3D printing can be used for the regeneration of complex tissues with intricate 3D microarchitecture. Trabecular bone is a complex and porous structure with a high degree of anisotropy. Changes in bone microarchitecture are associated with pathologies such as osteoporosis [1]. The objective of this study is to determine the viability of using 3D printing to replicate trabecular bone structures with a good control over the microarchitecture and mechanical properties. Cylindrical samples of bovine trabecular bone were used in this study. Micro-computed tomography (microCT) was carried out and an isotropic voxel size of 22 µm was obtained (Xradia Versa 520, Zeiss, USA). After 3D reconstruction the main microstructure characteristics were analysed using ImageJ (NIH, US). The 3D printed bone replicas were created by segmenting the microCT imaged bone tissue and then converted into a STL file using Avizo (FEI, US). The 3D printer used for this study was the ProJet 5500X (3D Systems, US), which allows a number of different materials to be printed in the same built with a resolution of 25 µm. Preliminary results were obtained using one single material (VisiJet CR-WT, Tensile Modulus: 1–1.6 GPa, Tensile Strength: 37–47 MPa). The 3D printed bone replicas followed a critical cleaning step to remove any remaining support material in the pores. MicroCT was then carried out for the bone replicas obtaining the same isotropic voxel size as for their biological counterparts. ImageJ was used to obtain the main microstructure characteristics. The values of bone volume fraction (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular spacing (Tb.Sp), and degree of anisotropy (DA) were measured for bone samples and their 3D printed replicas [2]. Preliminary results on the first bone sample with its 3D printed replica showed similar apparent trabecular structures. Their respective BV/TV was found to be 0.24 (bone) and 0.43 (replica). The Tb.Th and Tb.Sp were 0.222 mm and 0.750 mm respectively for the bone and 0.376 mm and 0.575 mm for the replica. Finally, their respective DA was found to be 0.68 (bone) and 0.66 (replica). The main microstructure characteristics analyzed showed some differences between the bone sample and the 3D printed replica. In particular, the 3D microstructures resulted over-dimensioned mainly due to factors such as microCT voxel size, resolution of the 3D printer and supporting material removal. However this is a preliminary investigation. Further analysis will focus on optimizing the microCT imaging as well as the 3D printing process to achieve more accurate bone replicas. In addition, multi-material printing will be employed to optimize some of the mechanical properties obtained through in situ microCT testing and FE subject-specific modelling