Design, Development, Testing at ISO standards and in-vivo feasibility study of a novel Polymeric Heart Valve Prosthesis

Clinically available prosthetic heart valves are life-saving, but imperfect: mechanical valves requiring anticoagulation therapy, whilst bioprosthetic valves have limited durability. Polymer valves offer the prospect of good durability without the need for anticoagulation. We report the design and development of a polymeric heart valve, its bench-testing at ISO standards, and preliminary extravivo and in-vivo short-term feasibility. Prototypes were manufactured by injection moulding of styrenic block copolymers to achieve anisotropic mechanical properties. Design was by finite element stress-strain modelling, which has been reported previously, combined with feedback from bench and surgery-based testing using various combinations of materials, valve geometry and processing conditions. Bench testing was according to ISO 5840:2015 standards using an in-vitro cardiovascular hydrodynamic testing system and an accelerated fatigue tester. Bench comparisons were made with a best-in-class bio-prosthesis. Preliminary clinical feasibility evaluations included extra-vivo and short-term (1-24 hours) in-vivo testing in a sheep model. The optimised final prototype met the requirements of ISO standards with hydrodynamic performance equivalent to the best-in-class bioprosthesis. Bench durability of greater than 1.2 billion cycles (30 years equivalent) was achieved (still ongoing). Extra-vivo sequential testing (n=8) allowed refinement of external diameter, 3D shape, a low profile, flexibility, suturability, and testing of compatibility to magnetic resonance imaging and clinical sterilisation. In vivo short-term (1-24 hours) feasibility (n=3) confirmed good suturability, no mechanical failure, no trans-valvular regurgitation, competitive trans-valvular gradients, and good biocompatibility at histopathology. We have developed and tested at ISO standards a novel prosthetic heart valve featuring competitive bench-based hydrodynamics and durability, well beyond the ISO requirements and comparable to a best-in-class bioprosthesis. In-vivo short-term feasibility testing confirmed preliminary safety, functionality and biocompatibility, supporting progression to a long-term efficacy trial.King's College, Cambridg

Synthesis of High Molecular Weight and Strength Polyisobutylene-Based Polyurethane and Its Use for the Development of a Synthetic Heart Valve

Under optimized synthesis conditions we prepared, for the first time, polyisobutylene-based polyurethane (PIB-PU) with 70% PIB soft segment (i.e., a bioinert and calcification resistant PU) with Mn >100,000 Da, 32 MPa ultimate strength and 630 % elongation. The key parameters for this achievement were (a) the precise stoichiometry of the polyurethane forming reaction, specifically the use of highly purified diisocyanate (MDI), and (b) the increased the solid content of the synthesis solution to the limit beyond which increased viscosity prevents stirring. The shape of the stress-strain trace of PIB-PU indicates two-step failure starting with a reversible elastic (Hookean) region up to ~50 % yield, followed by a slower linearly increasing high modulus deformation region suggesting the strengthening of PIB soft segments by entanglement/catenation, and the hard segments by progressively ordering urethane domains. This PIB-PUs is a candidate for a fully synthetic bioprosthetic heart valve since preliminary studies show that PIB-PU has impressive fatigue life.Armstrong Trust and Vice Chancellor's Scholarshi

Quenching of metal sticking by photo-oxidation of an amorphous semiconductor:Zn on GeS2

The sticking probability of Zn on amorphous GeS2 is greatly reduced when the UHV-prepared semiconductor film is photo-oxidized in the presence of band-gap radiation. The phenomena underlying this interesting effect have been elucidated in a kinetic and structural study using electron spectroscopy and x-ray-absorption spectroscopy. Selective photo-oxidation of Ge sites strongly suppresses the formation of Ge-Zn bonds at the interface: these act as nucleation sites for the growing metal film. A consistent picture emerges that also accounts for the very different behavior encountered during deposition of Ag films with and without photo-oxidation in the closely related Ag/GeS2 system.</p

The effect of photo-oxidation on the sticking and reactivity of Ag on amorphous GeS₂

Photo-oxidation of amorphous GeS2 films illuminated by band-gap radiation drastically alters the growth mode and reactivity of subsequently deposited Ag. In the former case (monolayer/simultaneous multilayer growth) the Ag reacts with both Ge and S sites. In the latter case (Stranski-Krastanov growth) Ge sites are selectively oxidized and film growth proceeds by Ag nucleation at the unoxidized S sites. The behaviour is very different from that reported earlier for Zn deposition on GeS2, where photo-oxidation results in very large changes in metal sticking probability. XPS, XAES and EXAFS data provide the basis for understanding both this phenomenon and the very different photodiffusion behaviour of Zn and Ag in GeS2.</p

Urban wildflower meadow planting for biodiversity, climate and society: An evaluation at King's College, Cambridge

Funder: Gatsby Charitable Foundation; doi: http://dx.doi.org/10.13039/501100000324Funder: King's College Cambridge, University of Cambridge; doi: http://dx.doi.org/10.13039/501100000648The biodiversity and climate crises are critical challenges of this century. Wildflower meadows in urban areas could provide important nature‐based solutions, addressing the biodiversity and climate crises jointly and benefitting society in the process. King's College Cambridge (England, UK) established a wildflower meadow over a portion of its iconic Back Lawn in 2019, replacing a fine lawn first laid in 1772. We used biodiversity surveys, Wilcoxon signed rank and ANOVA models to compare species richness, abundance and composition of plants, spiders, bugs, bats and nematodes supported by the meadow, and remaining lawn, over 3 years. We estimated the climate change impact of meadow vs lawn from maintenance emissions, soil carbon sequestration and reflectance effect. We surveyed members of the university to quantify the societal benefits of, and attitudes towards, increased meadow planting on the collegiate university estate. In spite of its small size (0.36 ha), the meadow supported approximately three times more plant species, three times more spider and bug species and individuals, and bats were recorded three times more often over the meadow than the remaining lawn. Terrestrial invertebrate biomass was 25 times higher in the meadow compared with the lawn. Fourteen species with conservation designations were recorded on the meadow (six for lawn), alongside meadow specialist species. Reduced maintenance and fertilising associated with meadow reduced emissions by an estimated 1.36 Mg CO2‐e per hectare per year compared with lawn. Relative reflectance increased by 25%–34% for meadow relative to lawn. Soil carbon stocks did not differ between meadow and lawn. Respondents thought meadows provided greater aesthetic, educational and mental wellbeing services than lawns. In open responses, lawns were associated with undesirable elitism and social exclusion (most colleges in Cambridge restrict lawn access to senior members of college), and respondents proved overwhelmingly in favour of meadow planting in place of lawn on the collegiate university estate. This study demonstrates the substantial benefits of small urban meadows for local biodiversity, cultural ecosystem services and climate change mitigation, supplied at lower cost than maintaining conventional lawn