Nanotechnology in vascular tissue engineering: from nanoscaffolding towards rapid vessel biofabrication :Nanotechnology in vascular tissue engineering: from nanoscaffolding towards rapid vessel biofabrication Vladimir Mironov, Vladimir Kasyanov and Roger R. Markwald Bioprinting Research Center, Department of Cell Biology and Anatomy, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA Mohana Marimuthu 200840090


Overview :Overview Introduction Nanotechnology - based control of cell behaviour - in bioengineering of athrombogenicity Nanostructuralized biomimetic vascular scaffolds Magnetic force driven vascular tissue engineering


Introduction :Introduction Bioreactor based – expensive, non automated Requirements of vascular graft: Should prevent - thrombosis - vascular intimal thickeneing - aneurysm Approaches - solid scaffold - a hydrogel - cell sheet


Slide 4:Nanostructuralized scaffold – mimic ECM Hydrogel – growth factors and ECM peptides – cell and tissue differentiation Nanotechnology – bioreactor free vascular tissue biofabrication


Control of cell behaviour :Control of cell behaviour Parameters of Biomaterials ECM ligands/growth factors – cell differentiation, maturation ligand density – cell behaviour – FRET Archeitectures Porous Nanofibres Hydrogels Solid scaffold Cell differentiation and cell behaviour


Slide 6:Centrifugal casting technology – solid scaffold + biofabrication of nanopatterned hydrogel Periodic mechanical stretching of cell membranes – magnetic nanoparticles – control cell fate


Bioengineering of Athrombogenicity :Bioengineering of Athrombogenicity 3 strategies – immobilization of athrombogenic molecules acellular thromboresistant nanosurfaces – immobilization of molecules – enhance endothelialization – enhancement of endothelialization – iron oxide nanoparticles or magnetic nanobeads – labelled endothelial cells


Slide 8:Amphiphilic lipid – like lumenal surfaces – athrombogenic phospholipid polymer Immobilization of CD34 antibodies – post implantational in-vivo endothelialization Nanocomposite bioactive peptides – endothelial monolayer by circulated progenitor cells


Nanostructuralized biomimetic vascular scaffolds :Nanostructuralized biomimetic vascular scaffolds Fabrication 1. Phase seperation 2. Electrospinning # nanofibers – size = natural ECM # mimic diameter- collagen fibrils of ECM # macropore structures # Collagen & elastin + synthetic polymers centrifugation/ vacuum - scaffolds rotation technology # Nanofiber meshwork cell attachment Spreading migration # one step fabrication integrated with living cells


Slide 11:3. Self assembly Collagen – structural component ECM – capable of self assembly # cross linking – 3 POG – disulfide # Chemical ligation – POG larger polymers – heterotrimer # heterotrimer – electrostatic interaction - stability Elastin – extensibility # Tropoelastin, elastin like polypeptides, recombinent polypeptides - mechanical property # low productivity, high cost


Magnetic force driven vascular tissue engineering :Magnetic force driven vascular tissue engineering Iron oxide nanoparticles – cells – by endocytosis – desirable location Cells labelled with magnetic microbeads – endothelium – driven by magnets Magnets – cell feeding, cell adhesion and monolayer assembly - cell retention


Slide 14:Cell sheet technololgy Challenge - undesirable cell activation by nanoparticles - intimal thickening Organ printing technology – robotic biofabrication of intraorgan vessels – vascular spheroids fused with tissues


Conclusion :Conclusion Overcome unsolved problems Bioreactor free methods Inexpensive Less time consuming Potential of nanotechnology – cost effective tissue engineered products


Slide 19:Thank you