Comparison of the Patency and Regenerative Potential of Biodegradable Vascular Prostheses of Different Polymer Compositions in an Ovine Model

Abstract

The lack of suitable autologous grafts and the impossibility of using synthetic prostheses for small artery reconstruction make it necessary to develop alternative efficient vascular grafts. In this study, we fabricated an electrospun biodegradable poly(ε-caprolactone) (PCL) prosthesis and poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) (PHBV/PCL) prosthesis loaded with iloprost (a prostacyclin analog) as an antithrombotic drug and cationic amphiphile with antibacterial activity. The prostheses were characterized in terms of their drug release, mechanical properties, and hemocompatibility. We then compared the long-term patency and remodeling features of PCL and PHBV/PCL prostheses in a sheep carotid artery interposition model. The research findings verified that the drug coating of both types of prostheses improved their hemocompatibility and tensile strength. The 6-month primary patency of the PCL/Ilo/A prostheses was 50%, while all PHBV/PCL/Ilo/A implants were occluded at the same time point. The PCL/Ilo/A prostheses were completely endothelialized, in contrast to the PHBV/PCL/Ilo/A conduits, which had no endothelial cells on the inner layer. The polymeric material of both prostheses degraded and was replaced with neotissue containing smooth-muscle cells; macrophages; proteins of the extracellular matrix such as type I, III, and IV collagens; and vasa vasorum. Thus, the biodegradable PCL/Ilo/A prostheses demonstrate better regenerative potential than PHBV/PCL-based implants and are more suitable for clinical use.

Multi-Omics Profiling of Human Endothelial Cells from the Coronary Artery and Internal Thoracic Artery Reveals Molecular but Not Functional Heterogeneity

“…Further, HCAECs and HITAECs overexpressed numerous functional molecular terms including synthesis of mitochondrial ribosomes, mitochondrial transcription and translation, energy generation in mitochondria, Ca 2+ -dependent signaling, secretion of extracellular vesicles, DNA metabolism and repair, RNA processing, ubiquitination, and autophagy. Such upregulation patterns suggested rapid metabolism to support the biosynthesis of ECM and BM components indicated above, similar to the scenario occurring in tissue-engineered vascular grafts during the replacement of biodegradable polymers with newly formed vascular tissue [119,120]. Another reason for active energy consumption is the need to support and regulate endothelial barrier semi-permeability during the vasoreactivity and regulation of blood pressure.…”

“…Equal amounts of the same protein lysates that were selected for proteomic profiling (10 µg per sample) were prepared for fluorescent Western blotting as previously described [120]. A Chameleon Duo Pre-Stained Protein Ladder (928-60000, LI-COR Biosciences, Lincoln, NE, USA) was loaded as a molecular weight marker.…”

“…A Chameleon Duo Pre-Stained Protein Ladder (928-60000, LI-COR Biosciences, Lincoln, NE, USA) was loaded as a molecular weight marker. The proteins were separated, and the protein transfer was performed using nitrocellulose transfer stacks as previously described [120]. Nitrocellulose membranes were then incubated in protein-free Block'n'Boost!…”

“…Incubation with the antibodies and fluorescent detection was performed using an Odyssey XF imaging system (LI-COR Biosciences, Lincoln, NE, USA) at a 700 nm channel (685 nm excitation and 730 nm emission). Total protein normalisation was conducted after the fluorescent detection using 0.1% Fast Green FCF (F8130, Solarbio Life Sciences, Beijing, China) as previously described [120]. The total protein visualisation was performed using an Odyssey XF imaging system (LI-COR Biosciences, Lincoln, NE, USA) in a 600 nm channel (520 nm excitation and 600 nm emission).…”

Bioengineered Small-Diameter Vascular Xenografts as an Alternative to Autologous Vascular Grafting for Emergency Revascularization – a Preliminary Study

“…The absence of proper autologous grafts and the unfeasibility of synthetic prostheses for small-diameter vascular reconstruction made mandatory the development of an alternative vascular graft. 11,12 The currently available synthetic grafts used in practice are made from expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate (Dacron). 13 They are used in large-diameter bypass grafting, preventing mechanical deformation in high-pressure and high-flow-rate arteries like the aorta.…”