Distinct Effects of Heparin and Interleukin-4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats.

Two of the greatest challenges for successful application of small-diameter in situ tissue-engineered vascular grafts are 1) preventing thrombus formation and 2) harnessing the inflammatory response to the graft to guide functional tissue regeneration. This study evaluates the in vivo performance of electrospun resorbable elastomeric vascular grafts, dual-functionalized with anti-thrombogenic heparin (hep) and anti-inflammatory interleukin 4 (IL-4) using a supramolecular approach. The regenerative capacity of IL-4/hep, hep-only, and bare grafts is investigated as interposition graft in the rat abdominal aorta, with follow-up at key timepoints in the healing cascade (1, 3, 7 days, and 3 months).

In Situ Remodeling Overrules Bioinspired Scaffold Architecture of Supramolecular Elastomeric Tissue-Engineered Heart Valves.

In situ tissue engineering that uses resorbable synthetic heart valve scaffolds is an affordable and practical approach for heart valve replacement; therefore, it is attractive for clinical use. This study showed no consistent collagen organization in the predefined direction of electrospun scaffolds made from a resorbable supramolecular elastomer with random or circumferentially aligned fibers, after 12 months of implantation in sheep. These unexpected findings and the observed intervalvular variability highlight the need for a mechanistic understanding of the long-term in situ remodeling processes in large animal models to improve predictability of outcome toward robust and safe clinical application.

Multi-component supramolecular fibers with elastomeric properties and controlled drug release.

Supramolecular materials based on hydrogen bonding ureido-pyrimidinones (UPy) are highly versatile substrates for tissue engineering, as they provide a platform in which specific functions can be introduced in a modular fashion by means of components with matching supramolecular motifs. In this work, a core-shell fiber mesh is generated by coaxial electrospinning of a robust elastomeric UPy-poly(hexamethylene carbonate) (UPy-PC) core with a hydrophilic shell of poly(ethylene glycol) (UPy-PEG), which is exploited to confer drug release properties to the load-bearing core. The effect of PEG chain length and supramolecular crosslink density on mechanical properties and drug elution profiles is investigated.

Biomechanical Behaviour and Biocompatibility of Ureidopyrimidinone-Polycarbonate Electrospun and Polypropylene Meshes in a Hernia Repair in Rabbits.

Although mesh use has significantly improved the outcomes of hernia and pelvic organ prolapse repair, long-term recurrence rates remain unacceptably high. We aim to determine the in vivo degradation and functional outcome of reconstructed abdominal wall defects, using slowly degradable electrospun ureidopyrimidinone moieties incorporated into a polycarbonate backbone (UPy-PC) implant compared to an ultra-lightweight polypropylene (PP) textile mesh with high pore stability. Twenty four New-Zealand rabbits were implanted with UPy-PC or PP to either reinforce a primary fascial defect repair or to cover (referred to as gap bridging) a full-thickness abdominal wall defect.

Experimental reconstruction of an abdominal wall defect with electrospun polycaprolactone-ureidopyrimidinone mesh conserves compliance yet may have insufficient strength.

Purpose: Electrospun meshes mimic the extracellular matrix, which may improve their integration. We aimed to compare polycaprolactone (PCL) modified with ureidopyrimidinone (UPy) electrospun meshes with ultra-lightweight polypropylene (PP; Restorelle) reference textile meshes for in vivo compliance. We chose UPy-PCL because we have shown it does not compromise biomechanical properties of native tissue, and because it potentially can be bioactivated.