Fabrication and Characterization of anti-coagulant loaded nanofibrous PLLA and PET scaffolds for Vascular Tissue Engineering Applications
Fabrication and Characterization of anti-coagulant loaded nanofibrous PLLA and PET scaffolds for Vascular Tissue Engineering Applications
Mahboubeh Kabiri,1,*Saba Aslani,2Romina Sepehri,3Chakavak Nojavan,4Payam Zahedi,5
1. Department of Biotechnology (straight Ph.D), College of Science, University of Tehran 2. Department of Biotechnology (straight Ph.D), College of Science, University of Tehran; Department of Neurology and Neurosurgery, McGill University, Quebec, Canada 3. University of Tehran 4. University of Tehran 5. University of Tehran
Introduction: The number of patients in need for vascular bypass grafting surgery is dramatically increasing, highlighting the development of functional small-diameter vascular grafts. Nevertheless, the high incidence of occlusion of tissue-engineered vascular grafts has remained a main challenge, leading to broad research in this specific field with a focus on construction of higher biocompatible grafts to inhibit or diminish blood clot formation. Local application of anti-coagulant agents can provide local anti-thrombotic effects.
Methods: Herein, in a series of studies we fabricated electrospun nanofibers from poly-L-lactic acid (PLLA) and poly-ether-sulfone. The PLLA scaffolds (Aligned or Random) were surface coated with Amniotic Membrane (AM) lysate for enhanced biocompatibility; and PET scaffolds were integrated with either carbon-nanotubes (CNT) or graphene oxide (GO) to make conductive substrates for endothelial cells attachment. Composition and ratios of the scaffolds were first optimized and the fabrication process was optimally developed. Also, we incorporated two main anti-coagulant agent (Aspirin and Heparin) in the fibers and assessed drug loading and release pattern into and out of the nanofibers, aiming to provide a local anti-coagulant releasing vehicle, directly inside the vascular grafts, where platelets would come across to and get activated. All three nanofibrous scaffolds were structurally and mechanically characterized and assessed for cyto- and hemo-compatibility.
Results: All different vascular constructs showed to have uniform, bead-less morphology with the fibers being in the range of nanometer. Plasma treatment made the scaffolds acceptingly hydrophilic and suitable for cell attachment. Anti-coagulant release profile showed a burst release followed by a constant release pattern over a 24-hour time window. The number and morphology of the platelets, assessed by SEM confirmed anti-activating and anti-platelet adhesion effects of drug loaded scaffolds compared to bare controls
Conclusion: Overall, our results together indicated that aspirin/heparin releasing PLLA and PET/GO PET/CNT scaffolds have appropriate physical and biochemical characteristics needed for a vascular graft with promising potential for further research towards development of the desirable small diameter vascular graft.