Robert D. Johnston

Aortic coarctation accounts for 5–8% of congenital heart disease and occurs in up to 6 in every 10,000 live births. While neonatal coarctation is typically treated surgically via thoracotomy and end-to-end anastomosis, endovascular stenting has become the preferred intervention in older children and adults. Despite favourable short-term outcomes, current stent therapies remain associated with long-term risks including persistent hypertension, and this may be linked to mostly off-label use of biliary stents which limit treatment efficacy in paediatric patients. Recent advances in additive manufacturing provide an opportunity to develop bespoke metallic stents tailored to patient-specific anatomy and biomechanics.,Here, we present a preclinical framework for the design, optimisation, fabrication, and evaluation of patient-specific stents for aortic coarctation treatment. Using selective laser melting (SLM) and finite element (FE) modelling, we developed a virtual design platform to generate and optimise Ti6Al4V stent geometries for varying severities of aortic narrowing (10%, 25%, 37.5%, and 50%). The resulting stent designs, with strut width and thickness dimensions ranging from 197.50 × 190.96 µm to 296.50 × 200 µm, were optimised to achieve a target post-expansion lumen diameter of 10 mm while minimising vessel wall stress. Furthermore, modifications to the connector geometry (original to C-connector and S-connector) enhanced stent conformability and reduced vessel wall stress by up to 16.7% and 19%, respectively. Candidate stents were subsequently fabricated by additive manufacturing, post-processed, and mechanically characterised in accordance with relevant regulatory testing standards. Finally, stent deployment was assessed computationally, through benchtop and ex vivo models to evaluate functional performance and deployment feasibility, establishing that optimised Ti6Al4V stents can be used for treatment of aortic coarctations.,Collectively, this work establishes an integrated computational and manufacturing workflow for the development of customised stents for aortic coarctation and demonstrates the potential of additive manufacturing to enable next-generation patient-specific cardiovascular implants.

Successful instrumented fusion of the lumbar spine is a complex surgical challenge, with positive patient outcomes dependent on careful surgical planning. Material selection is of critical importance to a mechanical construct supporting successful spinal fusion. Therefore, the aims of this study were to (a) evaluate the potential clinical use of finite element analysis (FEA) and (b) conduct a retrospective mechanical analysis of different implant materials in patients having undergone spinal fusion using FEA. Our methodology involved segmenting the spine from post-operative computed tomography (CT) image data from patients with previous spinal fusion. FEA models representing post-surgery cases were developed and different biomechanical loading conditions such as compression, flexion, bending and extension whilst testing pedicle screws of different materials were simulated. Patient specific finite element models were created, and biomechanical analysis were completed for all three patients. Polyetheretherketone (PEEK) constructs typically demonstrated lower peak implant stress when compared to titanium constructs for all spinal fusion levels. Furthermore, increasing the spinal fusion level resulted in significant differences in the maximum von Mises stress within both the bone and the instrumentation, whereas the 2-level fusion exhibited comparable stress levels in the bone irrespective of the instrumentation material. This pilot explores the potential of FEA as a clinical tool for assessing device and bone stresses. In our cohort, different materials can influence the stresses in both the instrumentation and the instrumented vertebrae, suggesting FEA can be useful pre- operative tool with regards to instrument selection and post-operatively to assess instrumentation and bone stresses. Graphical

Aortic stenosis is predominantly treated through transcatheter bioprosthetic heart valve implantation. However, the materials used in these devices are prone to premature failure. Polymer heart valves provide an alternative to current commercial devices, offering materials with greater durability and customisation through fibre reinforcement. Given the wide range of available materials and structures, there is a need for a systematic and efficient approach to designing and optimising novel bioinspired polymeric leaflets. This work presents a framework that employs computational modelling and Design of Experiments (DOE) tools to optimise bioinspired, 3D-printed, fibre-reinforced polymer leaflets made using melt electrowriting (MEW). Here, finite element (FE) models are created to represent MEW fibre-reinforced polymer leaflets for application in a transcatheter aortic heart valve. The behaviour of this valve under physiological loading conditions is modelled to predict valve performance and leaflet material response. These models were first used to investigate the impact of fibre orientation on valve performance and leaflet response, thereby demonstrating the benefits of a bioinspired fibre reinforcement structure. Using a DOE approach, the structural combination of MEW fibre reinforcement and an elastomeric matrix was optimised to improve valve performance and reduce leaflet stress and strain. Overall, the framework offers an efficient and versatile methodology for optimising fibre-reinforced polymer leaflets using an in silico approach, thereby reducing the need for physical prototyping and testing of these next-generation devices during early product development.

Visualising and quantifying vascular 3D microstructure are essential for linking it to mechanics and disease. This study evaluated Phospho-Tungstic Acid (PTA) and 1:2 Hafnium-substituted Wells Dawson Polyoxometalate (1:2 Hf-POM) as Contrast-Enhancing Staining Agents (CESAs) for X-ray based 3D Histology (X3DH) using Contrast-Enhanced Micro-focus Computed Tomography (CECT), as alternatives to classical 2D histology for visualising and quantifying collagen and elastin.Native and enzymatically digested porcine carotid artery segments, with varying elastin and collagen content, were CESA-stained and μCT-imaged to generate X3DH data, used to calculate Elastin-Stained Volume Fraction (E-SVF). Equivalent CESA-stained and unstained sections underwent Verhoeff’s (VH), Picrosirius Red (PR), and Haematoxylin–Eosin (H&E) histology to measure Elastin-Stained Area Fraction (E-SAF), Collagen-SAF (C-SAF), and cell density. X3DH results were compared with histology to evaluate correspondence and staining effects. Both CESAs produced strong signal colocalisation with elastic lamellae and weaker staining in the remaining ECM.E-SVF for both CESAs correlated strongly with E-SAF, but E-SVF values were about two times lower than E-SAF (r2PTA=0.86, p<0.0001, slopePTA=0.42 | r21:2-Hf-POM=0.86, p<0.0001, slope1:2-Hf-POM=0.49). This highlights CECT as a non-destructive, accurate method for quantifying vascular microstructure with fewer artefacts than classical 2D histology. VH and PR staining were visually and quantitatively (±10% E-SAF and C-SAF equivalence) unaffected by CESA-staining. PTA-staining with cryopreservation caused loss of nucleic contrast, while 1:2 Hf-POM influenced ECM haematoxylin uptake, reducing nuclei visualisation and cell count accuracy in H&E histology. Both CESAs bind non-specifically but preferentially to elastin, enabling reliable quantification. However, vascular collagen remains difficult to visualise as ECM is non-specifically stained.

The clinical decision to establish if a patient with carotid disease should undergo surgical intervention is primarily based on the percent stenosis. Whilst this applies for high-grade stenosed vessels (>70%), it falls short for other cases. Due to the heterogeneity of plaque tissue, probing the mechanics of the tissue would likely provide further insights into why some plaques are more prone to rupture. Mechanical characterization of such tissue is nontrivial, however, due to the difficulties in collecting fresh, intact plaque tissue and using physiologically relevant mechanical testing of such material. The use of polyvinyl alcohol (PVA) cryogel is thus highly convenient because of its acoustic properties and tunable mechanical properties. Methods. The aim of this study is to demonstrate the potential of PVA phantoms to simulate atherosclerotic features. In addition, a testing and simulation framework is developed for full PVA vessel material characterization using ring tensile testing and inflation testing combined with non-invasive ultrasound imaging and computational modeling. Results. Strain stiffening behavior was observed in PVA through ring tensile tests, particularly at high (n = 6) freeze–thaw cycles (FTCs). Inflation testing of bi-layered phantoms featuring lipid pool inclusions demonstrated high strains at shoulder regions. The application of an inverse finite element framework successfully recovered boundaries and determined the shear moduli for the PVA wall to lie within the range 27–53 kPa. Conclusion. The imaging-modeling framework presented facilitates the use and characterization of arterial mimicking phantoms to further explore plaque rupture. It also shows translational potential for non-invasive mechanical characterization of atherosclerotic plaques to improve the identification of clinically relevant metrics of plaque vulnerability.

Endovascular stenting of native aortic coarctation has become standard treatment for children and young adults due to the shorter hospital stay and recovery time, lower procedural risk and less invasive nature. However, despite these advantages, neonatal coarctation remains a surgically treated lesion, owing to the challenges of vessel growth and stent design. Plain old balloon angioplasty (POBA) of neonatal coarctation has been used as a treatment modality in the past but concern around vessel damage and aneurysm formation limited its widespread adoption. To-date, stenting has often been preferred over POBA treatment to minimise tissue damage but very little evidence has been gathered to establish the degree of tissue damage during intravascular procedures in neonatal coarctation tissue. The aim of this study was to perform balloon angioplasty and stenting on coarctation the aorta samples harvested at the time of surgery from neonatal patients and visualise the deformation under ultrasound guidance. From this, the novel collagen hybridizing peptide (CHP) was used to assess the level of collage denaturation and microstructural damage this tissue experienced when undergoing these procedures. The results demonstrate that balloon angioplasty singularly is not a viable treatment option at maintaining the lumen diameter unless higher levels of stretch are achieved to permanently deform the tissue. Five out of six neonatal coarctation samples were successfully stented with no stent failure, proving that stent insertion is a viable option to achieve the desired lumen diameter. In addition, for both procedures, increased collagen damage was observed with higher tissue strain. Overall, this work would suggest stent placement as the best option to achieve reliable lumen gain and to limit the level of the level of collagen damage when stretching the tissue to achieve the required lumen diameter.

The supracondylar foramen with a (seemingly) osseous peripheral arch noticed on the medio-distal feline humeri had remained disputed among anatomists. Some scholars have argued in favor of homology between this foramen and the supracondyloid foramen formed in presence of the ligament of Struthers in humans. Other theories include its presence as a retinaculum holding the median nerve and brachial artery to their anatomical position in a flexed elbow. Unfortunately, these theories lack investigative rigor. The emergence of non-invasive imaging modalities, such as micro-computed tomography, has enabled researchers to inspect the internal anatomy of bones without dismantling them. Thus, a micro-computed tomographic investigation was conducted on three feline (Felis catus) humeri specimens while the internal anatomy of the supracondylar foramina was examined. Unlike the humerus, the thin peripheral arch of the feline supracondylar foramen failed to elicit any osseous trabeculae or foci of calcification. While adhering to the humeral periosteum at its origin, the non-osseous arch, typical of a muscular tendon, attaches into the bony saddle related to the medial humeral epicondyle suggestive of a tendon or aponeurotic extension of a (vestigial) brachial muscle, with the coracobrachialis longus emerging to be the most likely candidate.