Challenges in the Development and Evaluation of Pediatric Heart Valve Technologies.

Background: In October 2022, the Heart Valve Collaboratory and Food and Drug Administration convened a global multidisciplinary workshop to address the unmet clinical need to promote and accelerate the development of pediatric-specific heart valve technologies.

Methods: The Pediatric Heart Valve Global Multidisciplinary Workshop was convened in October 2022. Key stakeholders, including expert clinicians in pediatric cardiology and cardiac surgery, valve manufacturers, engineers and scientists were assembled to review the current state-of-the-art, discuss unique challenges in the pre-and post-market evaluation of pediatric valve therapies, and highlight emerging technologies that show potential to address some of the key unmet needs of children with valve disease.

Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays.

In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available to treat CAVD because of the paucity of (i) appropriate experimental models that recapitulate this complex environment and (ii) benchmarking novel engineered aortic valve (AV)-model performance. We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, three-dimensional (3D)-bioprinted into 96-well arrays.

Inflammatory and regenerative processes in bioresorbable synthetic pulmonary valves up to two years in sheep-Spatiotemporal insights augmented by Raman microspectroscopy.

In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous heart valve restoration. Such scaffolds are designed to recruit endogenous cells in vivo, which subsequently resorb polymer and produce and remodel new valvular tissue in situ. Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo.

Tissue response, macrophage phenotype, and intrinsic calcification induced by cardiovascular biomaterials: Can clinical regenerative potential be predicted in a rat subcutaneous implant model?

The host immune response to an implanted biomaterial, particularly the phenotype of infiltrating macrophages, is a key determinant of biocompatibility and downstream remodeling outcome. The present study used a subcutaneous rat model to compare the tissue response, including macrophage phenotype, remodeling potential, and calcification propensity of a biologic scaffold composed of glutaraldehyde-fixed bovine pericardium (GF-BP), the standard of care for heart valve replacement, with those of an electrospun polycarbonate-based supramolecular polymer scaffold (ePC-UPy), urinary bladder extracellular matrix (UBM-ECM), and a polypropylene mesh (PP). The ePC-UPy and UBM-ECM materials induced infiltration of mononuclear cells throughout the thickness of the scaffold within 2 days and neovascularization at 14 days.

Increased utilization of bioprosthetic aortic valve technology:Trends, drivers, controversies and future directions.

: Bioprosthetic valves (BPV) implanted surgically or by transcatheter valve implantation (TAVI) comprise an overwhelming majority of substitute aortic valves implanted worldwide.: Prominent drivers of this trend are: 1) BPV patients have generally better outcomes than those with a mechanical valve, and remain largely free of anticoagulation and its consequences; 2) BPV durability has improved over the years; and 3) the expanding use of TAVI and valve-in-valve (VIV) procedures permitting interventional management of structural valve degeneration (SVD). Nevertheless, key controversies exist: 1) optimal anticoagulation regimens for surgical and TAVI BPVs; 2) the incidence, mechanisms and mitigation strategies for SVD; 3) the use of VIV for treatment of SVD, and 4) valve selection recommendations for difficult cohorts, (e.