An investigation into patient-specific 3D printed titanium stents and the use of etching to overcome Selective Laser Melting design constraints.

Due to limitations in available paediatric stents for treatment of aortic coarctation, adult stents are often used off-label resulting in less than optimal outcomes. The increasingly widespread use of CT and/or MR imaging for pre-surgical assessment, and the emergence of additive manufacturing processes such as 3D printing, could enable bespoke devices to be produced efficiently and cost-effectively. However, 3D printed metallic stents need to be self-supporting leading to limitations in their design. In this study, we investigate the use of etching to overcome these design constraints and improve stent surface finish. Furthermore, using a combination of experimental bench testing and finite element (FE) methods we investigate how etching influences stent performance. Then using an inverse finite element approach the material properties of the printed and etched stents were calibrated and compared. We show that without etching the titanium stents, the inverse FE approach underestimates the stiffness of the as-built stent (E = 33.89 GPa) when compared to an average of 76.84 GPa for the etched stent designs. Finally, using patient-specific finite element models the different stents' performance were tested to assess patient outcomes and lumen gain and vessel stresses were found to be strongly influenced by the stent design and postprocessing. Within this study, etching is confirmed as a means to create open-cell stent designs whilst still conforming to additive manufacturing 'rules' and concomitantly improving stent surface finish. Additionally, the feasibility of using an in-vivo imaging-to-product development pipeline is demonstrated that enables patient-specific stents to be produced for varying anatomies to achieve optimum device performance.

An in-silico Investigation Into the Role of Strain and Structure on Vascular Smooth Muscle Cell Growth.

The orientation of vascular cells can greatly influence the in vivo mechanical properties and functionality of soft vascular tissues. How cell orientation mediates the growth response of cells is of critical importance in understanding the response of soft tissues to mechanical stimuli or injury. To date, considerable evidence has shown that cells align with structural cues such as collagen fibers. However, in the presence of uniaxial cyclic strain on unstructured substrates, cells generally align themselves perpendicularly to the mechanical stimulus, such as strain, a phenomenon known as "strain avoidance." The cellular response to this interplay between structural cues and a mechanical stimulus is poorly understood. A recent in vitro experimental study in our lab has investigated both the individual and collective response of rat aortic smooth muscle cells (RASMC) to structural (collagenous aligned constructs) and mechanical (cyclic strain) cues. In this study, a 2D agent-based model (ABM) is developed to simulate the collective response of RASMC to varying amplitudes of cyclic strain (0-10%, 2-8%, 4-6%) when seeded on unstructured (PDMS) and structured (decellularized collagenous tissue) constructs. An ABM is presented that is fit to the experimental outcomes in terms of cellular alignment and cell growth on PDMS substrates, under cyclic strain amplitudes of (4-6%, 2-8%, 0-10%) at 24 and 72 h timepoints. Furthermore, the ABM can predict RASMC alignment and change in cell number on a structured construct at a cyclic strain amplitude of 0-10% after 10 days. The ABM suggests that strain avoidance behavior observed in cells is dominated by selective cell proliferation and apoptosis at these early time points, as opposed to cell re-orientation, i.e., cells perpendicular to the strain increase their rate of proliferation, whilst the rate of apoptosis simultaneously increases in cells parallel to the strain direction. The development of in-silico modeling platforms, such as that presented here, allow for further understanding of the response of cells to changes in their mechanical environment. Such models offer an efficient and robust means to design and optimize the compliance and topological structure of implantable devices and could be used to aid the design of next-generation vascular grafts and stents.

An in vitro model quantifying the effect of calcification on the tissue-stent interaction in a stenosed aortic root.

Transcatheter Aortic Valves rely on the tissue-stent interaction to ensure that the valve is secured within the aortic root. Aortic stenosis presents with heavily calcified leaflets and it has been proposed that this calcification also acts to secure the valve, but this has never been quantified. In this study, we developed an in vitro calcified aortic root model to quantify the role of calcification on the tissue-stent interaction. The in vitro model incorporated artificial calcifications affixed to the leaflets of porcine aortic heart valves. A self-expanding nitinol braided stent was deployed into non-calcified and artificially calcified porcine aortic roots and imaged by micro computed tomography. Mechanical tests were then conducted to dislodge the stent from the aortic root and it was found that, in the presence of calcification, there was a significant increase in pullout force (8.59 ±â€¯3.68 N vs. 2.84 ±â€¯1.55 N p = 0.045), stent eccentricity (0.05 ±â€¯0.01 vs. 0.02 ±â€¯0.01, p = 0.049), and coefficient of friction between the stent and aortic root (0.36 ±â€¯0.12 vs. 0.09 ±â€¯0.05, p = 0.018), when compared to non-calcified roots. This study quantifies for the first time the impact of calcification on the friction between the aortic tissue and transcatheter aortic valve stent, showing the role of calcification in anchoring the valve stent in the aortic root.

The impact of implantation depth of the Lotus™ valve on mechanical stress in close proximity to the bundle of His.

It has been proposed that inappropriate positioning of transcatheter aortic valves (TAVs) is associated with procedural complications and decreased device durability. Second-generation TAVs allow for repositioning giving greater control over the final deployment position. However, the impact of positioning on the tissue surrounding these devices needs to be better understood, in particular for the interleaflet triangle in which the conductance system (bundle of His) resides. In this study, we investigate the impact of implantation depth on the frame-tissue interaction for a next-generation repositionable Lotus™ valve. For this purpose, a computational model simulating deployment of the Lotus valve frame into a calcified patient-specific aortic root geometry was generated to predict aortic root stress and frame eccentricity at three different deployment depths. The results of this study predicted that positioning of the Lotus valve had an influence on the stresses in the aortic sinus and frame eccentricity. An analysis of levels of stress arising in the vicinity of the bundle of His, as a function of implantation depth, was conducted, and it was found that, for the specific patient anatomy studied, although the sub-annular position showed reduced peak stress in the aortic sinus, this implantation position showed the highest stress in the area of greatest risks of conductance interference. In contrast, while a supra-annular position increased the peak arterial stress, this implantation position resulted in lower stress in the interleaflet triangle and thus might reduce the risk of conductance interference. These results provide pre-operative information that can inform clinical decision-making regarding TAVI positioning.