No abstract

Transcatheter valve replacement indication is currently being extended to younger and lower-risk patients. However, transcatheter prostheses are still based on glutaraldehyde-fixed xenogeneic materials. Hence, they are prone to calcification and long-term structural degeneration, which are particularly accelerated in younger patients. Tissue-engineered heart valves based on decellularized in vitro grown tissue-engineered matrices (TEM) have been suggested as a valid alternative to currently used bioprostheses, showing good performance and remodeling capacity as transcatheter pulmonary valve replacement (TPVR) in sheep. Here, we first describe the in vitro development of human cell-derived TEM (hTEM) and their application as tissue-engineered sinus valves (hTESVs), endowed with Valsalva sinuses for TPVR. The hTEM and hTESVs were systematically characterized in vitro by histology, immunofluorescence, and biochemical analyses, before they were evaluated in a pulse duplicator system under physiological pulmonary pressure conditions. Thereafter, transapical delivery of hTESVs was tested for feasibility and safety in a translational sheep model, achieving good valve performance and early cellular infiltration. This study demonstrates the principal feasibility of clinically relevant hTEM to manufacture hTESVs for TPVR.

In this work, a novel approach for the functionalization of electrospun stereocomplex polylactide (sc-PLA)-based fibers, prepared from solutions containing equimolar amount of high-molecular-weight poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), was developed. The method, which consists in introducing functionalized polyhedral oligomeric silsesquioxanes (POSS) into the electrospinning solutions, was carried out by employing as a solvent system a 2:1 mixture of chloroform (CHCl 3 ) and 1,1,1,3,3,3hexafluoro-2-propanol (HFIP), never applied in the production of sc-PLA fibers, which was found to promote POSS solubilization while simultaneously allowing to obtain an excellent fiber homogeneity. Indeed, the specific effect of the single components of the solvent mixture, CHCl 3 and HFIP, on fiber structuring and morphology was evaluated. Conversely to the fiber morphology, which turned out to be significantly affected by the chosen electrospinning solvent, the PLA stereocomplexation, occurring upon subsequent annealing treatment at 100 °C (as evidenced by differential scanning calorimetry (DSC) and X-ray diffraction analyses), was found to be similar for fibers prepared starting from the different types of solvent. Unlike solution casting, electrospinning allows the exclusive formation of stereocomplex crystallites, simultaneously promoting a submicrometric dispersion of the silsesquioxanes, with the consequent fiber functionalization. In our work, two different kinds of POSSone characterized by hydroxyl groups (POSS−OH) and another one functionalized with an aminobearing molecule (POSS−NH 2 )were exploited to impart hydroxyl and amino functionalities to PLA based nanofibers, while preserving the capability of the polymer system to form a pure stereocomplex on subsequent annealing. In particular, it was found that the amino groups of the sc-PLA fibers functionalized with POSS−NH 2 , promote specific interactions with a metal precursor, i.e., PdCl 2 , which, as a result of a subsequent reduction, forms metal nanoclusters homogeneously dispersed on the fiber surface. The higher thermal and chemical resistance of the sc-PLA fibers with respect to those based solely on PLLA allowed to significantly broaden the applications of the catalytic system. Indeed, the sc-PLA/Pd fibers turned out to be very active in the Heck reaction, easily recoverable and reusable for multiple catalytic cycles.

No abstract

Supramolecular fibers fabricated by co-axial electrospinning combine load-bearing properties and sustained drug release of hydrophobic and UPy-modified drugs.