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Numerous cardioprotective interventions have been reported to reduce myocardial infarct size (IS) in pre-clinical studies. However, their translation for the benefit of patients with acute myocardial infarction (AMI) has been largely disappointing. One reason for the lack of translation is the lack of rigor and reproducibility in pre-clinical studies. To address this, we have established the European IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) pig AMI network with centralized randomization and blinded core laboratory IS analysis and validated the network with ischemic preconditioning (IPC) as a positive control. Ten sites in the COST Innovators Grant (IG16225) network participated in the IMPACT network. Three sites were excluded from the final analysis through quality control of infarct images and use of pre-defined exclusion criteria. Using a centrally generated randomization list, pigs were allocated to myocardial ischemia/reperfusion (I/R, N = 5/site) or IPC + I/R (N = 5/site). The primary endpoint was IS [% area-at-risk (AAR)], as quantified by triphenyl-tetrazolium-chloride (TTC) staining in a centralized, blinded core laboratory (5 sites), or IS [% left-ventricular mass (LV)], as quantified by a centralized, blinded cardiac magnetic resonance (CMR) core laboratory (2 sites). In pooled analyses, IPC significantly reduced IS when compared to I/R (57 ± 14 versus 32 ± 19 [%AAR] N = 25 pigs/group; p < 0.001; 25 ± 13 versus 14 ± 8 [%LV]; N = 10 pigs/group; p = 0.021). In site-specific analyses, in 4 of the 5 sites, IS was significantly reduced by IPC when compared to I/R when quantified by TTC and in 1 of 2 sites when quantified by CMR. A pig AMI multicenter European network with centralized randomization and core blinded IS analysis was established and validated with the aim to improve the reproducibility of cardioprotective interventions in pre-clinical studies and the translation of cardioprotection for patient benefit., Competing Interests: Declarations. Conflict of interest: P.F. is the founder and CEO and ZG is involved in the management of Pharmahungary Group, a group of R&D companies. Pharmahungary Group has a conflict of interest as it may be organizing multicenter studies on cardioprotection on external request and potentially including the here validated sites of the current COST action (IG16225). D.J.H. has received: consultant fees from Faraday Pharmaceuticals Inc. and Boehringer Ingelheim International GmbH; honoraria from Servier; and research funding from Astra Zeneca, Merck Sharp & Dohme Corp and Novonordisk. J. L. Z. received speaker honoraria from Pfizer, Bayer, Novartis, and Amgem. All other authors declare no competing interests. Ethical statements: The experimental protocols conformed to the EU directive 2010/63EU on the protection of animals used for scientific purposes and the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines [49]. The experimental protocols were formally approved by the appropriate national or institutional ethics committees (see Suppl. Data sheet experimental design)., (© 2024. The Author(s).)

Objective: Hemodialysis patients usually receive an arteriovenous fistula (AVF) in the arm as vascular access conduit to allow dialysis 2-3 times a week. This AVF introduces the high flow necessary for dialysis, but over time the ever-present supraphysiological flow is the leading cause of complications. This study aims to develop an implantable device able to non-invasively remove the high flow outside dialysis sessions., Methods: The developed prototype features a magnetic ring allowing external coupling and torque transmission to non-invasively control an AVF valve. Mock-up devices were implanted into arm and sheep cadavers to test sizes and locations. The transmission torque, output force, and valve closure are measured for different representative skin thicknesses., Results: The prototype was placed successfully into arm and sheep cadavers. In the prototype, a maximum output force of 78.9 ± 4.2 N, 46.7 ± 1.9 N, 25.6 ± 0.7 N, 13.5 ± 0.6 N and 6.3 ± 0.4 N could be achieved non-invasively through skin thicknesses of 1-5 mm respectively. The fistula was fully collapsible in every measurement through skin thickness up to the required 4 mm., Conclusion: The prototype satisfies the design requirements. It is fully implantable and allows closure and control of an AVF through non-invasive torque transmission. In vivo studies are pivotal in assessing functionality and understanding systemic effects., Significance: A method is introduced to transfer large amounts of energy to a medical implant for actuation of a mechanical valve trough a closed surface. This system allows non-invasive control of an AVF to reduce complications related to the permanent high flow in conventional AVFs.

Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.

Background: Congenital obstructive hydrocephalus generates progressive irreversible fetal brain damage by ventricular enlargement and incremental brain tissue compression that leads to maldevelopment and poor clinical outcomes. Intrauterine treatments such as ventriculo-amniotic shunting have been unsuccessfully tried in the eighties., Objective: To assess if prenatal endoscopic third ventriculostomy (ETV) is feasible in a large animal model and optimize this technique for ventricular decompression and potential arrest of fetal brain damage in fetal lambs., Methods: We generated hydrocephalus in 50 fetal lambs by injecting a polymeric agent into the cisterna magna at midgestation (E85). Subsequently, 3 weeks later (E105), fetal ETV was performed using a small rigid fetoscope. The endoscopy entry point was located anterior to the coronal suture, 7 mm from the midline., Results: We obtained clear visualization of the enlarged lateral ventricles by endoscopy in the hydrocephalic fetal lambs. The floor of the third ventricle was bluntly perforated and passed with the scope for a successful ETV. Total success was achieved in 32/50 cases (64%). Causes of failure were blurred vision or third ventricle obliteration by BioGlue in 10/50 (20%) cases, anatomic misdirection of the endoscope in 5 (10%) cases, 2 cases of very narrow foramen of Monro, and 1 case of choroid plexus bleeding. If we exclude the cases artificially blocked by the polymer, we had a successful performance of prenatal-ETV in 80% (32/40) of hydrocephalic fetuses., Conclusion: Despite the inherent difficulties arising from ovine brain anatomy, this study shows that innovative fetal ETV is technically feasible in hydrocephalic fetal lambs., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Tissue engineering is a promising methodology to produce advanced therapy medicinal products (ATMPs). We have developed personalized tissue engineered veins (P-TEV) as an alternative to autologous or synthetic vascular grafts utilized in reconstructive vein surgery. Our hypothesis is that individualization through reconditioning of a decellularized allogenic graft with autologous blood will prime the tissue for efficient recellularization, protect the graft from thrombosis, and decrease the risk of rejection. In this study, P-TEVs were transplanted to vena cava in pig, and the analysis of three veins after six months, six veins after 12 months and one vein after 14 months showed that all P-TEVs were fully patent, and the tissue was well recellularized and revascularized. To confirm that the ATMP product had the expected characteristics one year after transplantation, gene expression profiling of cells from P-TEV and native vena cava were analyzed and compared by qPCR and sequencing. The qPCR and bioinformatics analysis confirmed that the cells from the P-TEV were highly similar to the native cells, and we therefore conclude that P-TEV is functional and safe in large animals and have high potential for use as a clinical transplant graft.