EPITHELIALIZATION:EPITHELIALIZATION:Massachusetts Institute of TechnologMassachusetts Institute of TechnologyHarvard Medical SchooHarvard Medical SchoolHarvard Medical SchoolHarvard Medical SchoolBrigham and Women’s/Massachusetts General HospBrigham and Women’s/Massachusetts General Hosp.VA Boston Healthcare SystemVA Boston Healthcare System2.79J/3.96J/20.441/HST522J2.79J/3.96J/20.441/HST522JENDOTHELIALIZATION EPITHELIALIZATION:EPITHELIALIZATION:ENDOTHELIALIZATIONM. Spector, Ph.DM. Spector, Ph.D.M. Spector, Ph.D.M. Spector, Ph.D.•• Permanent biomaterials for thePermanent biomaterials for the fabrication of vascular prosthesesfabrication of vascular prostheses•• Biomaterials for scaffolds for blood vesselBiomaterials for scaffolds for blood vessel tissue engineeringtissue engineeringBLOOD VESSELSDiagrams of healing process (cell migratioDiagrams of healing process (cell migration, mitosis) removed due to copyright restrictions. Epidermal Wound HealingVein Artery Diagrams of removed due to copyright restrictions. Endothelial Intimacells Media Smooth muscle cells muscle cells Vein Artery Adventitia Vein Artery Diagrams of removed due to copyright restrictions. Endothelial cells Intima MediaSmooth muscle cells––tt••TunicaTunica intimaintimail l fill fsingle layer ofsingle layer ofendotheliumendothelium••TunicaTunica mediamedia–– circumferential layercircumferential layerof smooth muscle cellsof smooth muscle cells ••TunicaTunica adventitiaadventitia(externa)(externa) fib ifib i––fibrous connectivefibrous connective tissuetissueFigure by MIT OpenCourseWare. BLOOD VESSEL HISTOLOGYEXAMPLE OF A HOLLOW, LAYERED STRUCTURE THE VASCULAR WALL Epithelial cells Muscle cells Connective tissue cells Diagram removed due to copyright restrictions. Detailed structure of vascular wall. Figure by MIT OpenCourseWare Netter FH, Heart , The Ciba Collection, 1969Ph t d d t i ht t i tiVein Artery Photo removed due to copyright restrictions. Histology photo comparing vein and artery vascular wall structures.Normal coronary artery Lipid deposits in the wall Two histology photos removed due to copyright restrictions.J NIH 5:100 (1993)Cardiac Infarct Resulting from Coronary Artery OcclusionCoronary Artery Occlusion Left Anterior Descending Diagram removed due to copyright restrictions. Zone of infarct Left Anterior Descending Functional Anatomy of the HeartImage removed due to copyright restrictions. Figure 3 in Michaels, A. D., and K. Chatterjee. “Angioplasty Versus Bypass Surgery for Coronary Artery Disease.” Circulation 106 (2002):yp g y y y ( ) e187-e190. DOI: 10.1161/01.CIR.0000044747.37349.64 F. Schoen F. SchoenAnastomotic Hyperplasia in an ePTFE Femoropopliteal GraftFemoropopliteal Graft Image removed due to copyright restrictions. Source: Schoen, F. J, and R. S. Cotran. “Blood Vessels.” In Pathologic Basis of Disease, 6th edition. Saunders, 1999. p. 537. F. SchoenF. Schoen F. SchoenVascular Response to Injury: Rabbit Model EC Endothelial Cells EC SMC Muscle Cells CT Connective Tissue CT EC SMCSMC Two histology photos removed due to copyright restrictions. CT F. SchoenF. Schoen••Permanent artificial vesselPermanent artificial vesselsPermanent artificial vesselsPermanent artificial vessels•• Autografts (saphenous vein)Autografts (saphenous vein)Ti i d bl d lTi i d bl d l••Tissue engineered blood vesselTissue engineered blood vesselVASCULAR IMPLANTSVASCULAR PROSTHESES Graft Size Type Used LLarge di ter (12(12 -38Aortdiamet38 mm)); Ata Pl th l t hthlt (PET D )Polyethyleneterephthalate (PET; Dacron) Medium diam. (5-10 mm); Femoral artery PET, polytetrafluoroethylene (PTFE; Teflon) Small diam. (< 4 mm); cerebral/coronary Vessel autografts; Saphenous vein • The distinction between large and small diameter vessel replacements is arbitrarily based on the degree of blood compatibility. • Dacron was introduced into America in 1946 as a polyester polymer of ethylene glycol and terephthalic acid; Polytetrafluoroethylene (Teflon) first became available as aand terephthalic acid; Polytetrafluoroethylene (Teflon) first became available as a multifilament yarn in 1954. – PET and PTFE conduits do not deteriorate after implantation. – Strong, nonreactive, noncarcinogenic and tend to retain tensile strength id fi it ely. indefinitl • Nearly all large diameter vascular prostheses are made of Dacron (Bard and Meadox). – 75% are bifurcated (replace the lower ppart of the aorta where it branches into the (p femoral arteries); 25% are straight. • 70 % of the medium diameter Gore-Tex; 25% Dacron; and 5% biologicals. • Currently only 1 % of the small diameter market is held by synthetic grafts due tolack of blood compatible materialslack of blood compatible materials. http://www.biomed.metu.edu.tr/courses/term_papers/BurcuUnal.htmBifurcated Grafts Photo removed due to copyright restrictions.copyright restrictions.Photos of textile vascular prostheses removed due to Photos of textile vascular prostheses removed due to copyright restrictions. Hemashield Gold ™ grafts from Boston Scientific.--I di l f ll i i l i h li i f h f i lI di l f ll i i l i h li i f h f i lPl l dh hPl l dh hi l i li l i lfib i l d f h jfib i l d f h jShortly after a Dacron graft is exposed to arterial blood flow, a predictablShortly after a Dacron graft is exposed to arterial blood flow, a predictablesequence of events occurs.sequence of events occurs.•• Fibrin is absorbed onto the inner graft surface.Fibrin is absorbed onto the inner graft surface.••In largeIn large--diam prostheses subjected to high volume flow this fibrin layerdiam prostheses subjected to high volume flow this fibrin layerIn largeIn largediam. prostheses subjected to high volume flow this fibrin layerdiam. prostheses subjected to high volume flow this fibrin layerusually remains thin, typically less than 1 mm.usually remains thin, typically less than 1 mm.•• In smallerIn smaller--diam. Dacron prostheses in low flow environments, the fibrin layediam. Dacron prostheses in low flow environments, the fibrin layermay increase in thickness, ultimately promoting graft occlusion.may increase in thickness, ultimately promoting graft occlusion.••Immediately following implantation the outer lining of the graft is alsoImmediately following implantation the outer lining of the graft is also completely encapsulated with fibrin.completely encapsulated with fibrin.––