Stents for transcatheter aortic valve replacement

Rheumatic heart disease (RHD) is the leading cause of aortic valve disease in the world. Surgery to repair or replace the diseased valves is the only means to save a patient's life once the disease becomes symptomatic. Transcatheter aortic valve replacement (TAVR) has revolutionised the treatment of age-related degenerative aortic valve disease, but is currently not suitable for the majority of RHD sufferers due to the rapid degeneration of flexible leaflet valves in younger patients, contraindications of commercial devices to regurgitant or non-calcific aortic valve disease, and also due to resource or funding limitations. The current research project aimed to develop and test novel compressible balloon-expandable stents suitable for patients with symptomatic rheumatic aortic valve disease, and which would allow for a percutaneous polymeric valve to be manufactured, be crimped onto balloon-based devices, and be expanded into a compliant or non-calcific native aortic valve. Several stent concepts were developed and evaluated using Finite Element Analysis (FEA) and two favoured concepts were selected for more complex FEA, in which the balloon was simulated using an Ogden material model, and rigorous testing. The stent material, a nickel-cobalt-chromium alloy, was modelled as an isotropic elasto-plastic material with isotropic hardening. The novel stent designs incorporated a native leaflet-mimicking crown shape for continuous leaflet attachment and mechanisms to anchor the stented valve within compliant aortic roots. The first of the favoured designs provided tactile location during delivery and anchored using self-expanding arms on a balloon-expandable frame of the same material ("self-locating stents"). The second design anchored using arms that protruded during deployment as a consequence of plastic deformation incurred during crimping ("expanding arm stents"). Prototypes were successfully manufactured through laser cutting and electropolishing and showed good surface quality. In vitro testing included determination of crimping and expansion behaviour and measurement of mechanical properties such as resistance to migration in the anatomy. Valve performance was evaluated through in vitro haemodynamics in a pulse duplicator and durability was tested in a high-cycle fatigue tester. Simulated use testing was performed using cadaveric animal hearts. Finally, valves were also implanted into the aortic valve position of pigs (in acute termination experiments) through a transapical approach in order to verify valve deployment behaviour and function in vivo, and determine the stent's ability to anchor in the native anatomy. Stents could be crimped to diameters below 6mm and deployed using commercial balloons and proprietary non-occlusive deployment devices. FEA simulations of stent crimping and deployment matched experimental behaviour well and provide a tool to optimise stent performance. Peak Von Mises stresses during deployment (1437 MPa and 1633 MPa for self-locating and expanding arm stents, respectively) were comparable to a "zig-zag" stent simulated for control purposes (1650 MPa). Radial strength, evaluated for expanding arm stents, was lower than the Control stent (116 N vs. 347 N). This design, although predicted to be safe under fatigue loading, had a lower fatigue safety factor than the Control stent. Stents resisted migration to forces of at least 22 N, which is four times greater than physiological loading on the valves. Polymeric valves incorporating the stents were constructed and demonstrated good in vitro haemodynamic performance (Effective Orifice Areas ≥2.0cm², ΔP<9 mmHg, regurgitation <6%) and durability of over 400 million cycles. Designs functioned as intended in simulated use tests. Valves constructed using self-locating stents could be successfully deployed without rapid pacing in eight of nine pigs, and valve position was correct in seven of these. Valves of expanding arm stents remained anchored in six of eight attempted implants in pigs. This study has demonstrated proof of concept for a novel balloon-expandable stent for a polymeric transcatheter heart valve that is capable of anchoring in a compliant native aortic valve

The PATH study: Preparing for the Adoption of innovative hearing THerapies

BACKGROUND: Innovative drug, gene and cell therapies are being developed to address the unmet clinical need of people with hearing loss. With approval for clinical use on the horizon in the next 5 years, it is essential to start preparing for the implementation of these therapies in hearing healthcare services. AIM: To provide stakeholders who develop, will use and pay for innovative hearing therapies, with a detailed understanding of the elements that influence their adoption and implementation and with practical strategies to facilitate their uptake in the UK healthcare system. METHOD: 1) To inform product development and decisions on value for money, I constructed an early health economic model with input data from literature searches and 26 interviews. 2) To characterise and understand the elements that influence the adoption and implementation of innovative hearing therapies in the UK healthcare system, I conducted 37 semi-structured interviews drawing upon insights from the early health economic model. 3) To add to this understanding, I performed a hermeneutic review of elements that influence the adoption and implementation of innovative therapies in general. 4) To integrate the findings from my thesis, I constructed a framework that maps the elements that influence innovative hearing therapy adoption and implementation, and that summarises practical strategies to facilitate uptake. RESULTS: I found that alliances between clinicians, scientists, patients, biotechnology and hearing technology companies can facilitate adoption of innovative hearing therapies, benefitting from pooled resources, diffusion networks and established market access. Timely clinician education can break down engrained clinical practices and gain clinician buy-in. Early engagement with patients can help ensure these therapies meet patient needs and generate patient and public interest, which can influence clinician uptake and policy decisions. Precision diagnostics are critical to the development and uptake of innovative hearing therapies; co-development strategies and novel regulatory pathways can accelerate their development. Accelerator organisations can help navigate healthcare systems, assist with manufacturing and distribution strategies, support clinical trialing, help develop business cases, and lobby decision makers. Additional insights revealed that novel payment strategies and robust business cases can help make procurement affordable and avoid delays in adoption. Real world data can increase confidence to take-up innovative hearing therapies, support payment strategies, early access programs and help fulfil regulatory requirements. CONCLUSION: My research has resulted in a framework that can accelerate the uptake of innovative hearing therapies across healthcare systems. Stakeholders can use my framework to gain detailed information on the processes that need to take place for adoption and implementation of these therapies as well as strategies to facilitate these processes

1st EFORT European Consensus: Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices

Innovations in Orthopaedics and Traumatology have contributed to the achievement of a high-quality level of care in musculoskeletal disorders and injuries over the past decades. The applications of new implants as well as diagnostic and therapeutic techniques in addition to implementation of clinical research, have significantly improved patient outcomes, reduced complication rates and length of hospital stay in many areas. However, the regulatory framework is extensive, and there is a lack of understanding and clarity in daily practice what the meaning of clinical &amp; pre‐clinical evidence as required by the MDR is. Thus, understanding and clarity are of utmost importance for introduction of new implants and implant-related instrumentation in combination with surgical technique to ensure a safe use of implants and treatment of patients. Therefore EFORT launched IPSI, The Implant and Patient Safety Initiative, which starting from an inaugural workshop in 2021 issued a set of recommendations, notably through a subsequent Delphi Process involving the National Member Societies of EFORT, European Specialty Societies as well as International Experts. These recommendations provide surgeons, researchers, implant manufacturers as well as patients and health authorities with a consensus of the development, implementation, and dissemination of innovation in the field of arthroplasty. The intended key outcomes of this 1st EFORT European Consensus on “Medical &amp; Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices”are consented, practical pathways to maintain innovation and optimisation of orthopaedic products and workflows within the boundaries of MDR 2017/745. Open Access practical guidelines based on adequate, state of the art pre-clinical and clinical evaluation methodologies for the introduction of joint replacements and implant-related instrumentation shall provide hands-on orientation for orthopaedic surgeons, research institutes and laboratories, orthopaedic device manufacturers, Notified Bodies but also for National Institutes and authorities, patient representatives and further stakeholders. We would like to acknowledge and thank the Scientific Committee members, all International Expert Delegates, the Delegates from European National &amp; Specialty Societies and the Editorial Team for their outstanding contributions and support during this EFORT European Consensus

2014 - 2015 University Catalog

This is a one-year Catalog, effective beginning Summer Quarter 2014. Volume 104, Number 1, July 2014https://scholarsrepository.llu.edu/univcatalog/1002/thumbnail.jp

Small caliber arterial prosthesis: prototype and pre-industrialization

Cardiovascular diseases represent the leading cause of death in developed countries. Modern surgical methods show poor efficiency in the substitution of small-diameter arteries (< 6 mm). Due to the mismatch in mechanical properties between the native artery and the substitute, the behavior of the vessel wall remains a major cause of inefficient substitutions an unsolved complication in surgery since 1970. The purpose of this work was to obtain polylysine-enriched vascular substitutes, derived from decellularized porcine femoral and carotid arteries. Polylysine was selected as a matrix cross-linker, increasing the mechanical resistance of the scaffold with respect to decellularized vessels, without altering the native biocompatibility and haemocompatibility properties. The biological characterization showed excellent biological performances, while mechanical tests displayed that the Young’s modulus of the polylysine-enriched matrix was comparable to that of the native vessel. Concerning haemocompatibility, the performed analyses show that polylysine-enriched matrices increase coagulation time, with respect to commercial Dacron® vascular substitutes. Based on these findings, polylysine-enriched decellularized vessels resulted in a promising approach for vascular substitution. In order to consider the industrial phase, a business plan (BP) and the preengineering of the production reactor were developed in the present project. Is crucial to consider the scale-up process of the project from the initial stages to increase the chances of its success. In this way, the feasibility study will contemplate the viability of the project from an economic point of view thus, the BP is the most important document of the study. From an engineering point of view, the industrial production reactor is the heart of the plant, so designing it from the outset will allow considering costs and performing the necessary experiments for its final design