Fremstilling af små Caliber stentimplantater Brug Electrospinning og Balloon kan udvides Bare Metal Stents
Summary
In the protocol, we present a method to manufacture a small caliber stent-graft by sandwiching a balloon expandable stent between two electrospun nanofibrous polyurethane layers.
Abstract
Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and perforations in vasculature. Such stent-grafts are manufactured by covering a stent with a polymer membrane. An ideal stent-graft should have a biocompatible stent covered by a porous, thromboresistant, and biocompatible polymer membrane which mimics the extracellular matrix thereby promoting injury site healing. The goal of this protocol is to manufacture a small caliber stent-graft by encapsulating a balloon expandable stent within two layers of electrospun polyurethane nanofibers. Electrospinning of polyurethane has been shown to assist in healing by mimicking native extracellular matrix, thereby promoting endothelialization. Electrospinning polyurethane nanofibers on a slowly rotating mandrel enabled us to precisely control the thickness of the nanofibrous membrane, which is essential to achieve a small caliber balloon expandable stent-graft. Mechanical validation by crimping and expansion of the stent-graft has shown that the nanofibrous polyurethane membrane is sufficiently flexible to crimp and expand while staying patent without showing any signs of tearing or delamination. Furthermore, stent-grafts fabricated using the methods described here are capable of being implanted using a coronary intervention procedure using standard size guide catheters.
Introduction
Koronar intervention procedurer forårsage betydelig karvæggen skade som følge af afbrydelse af plak og karvæggen. Dette resulterer i restenose, perifer emboli hos vene transplantater, og diskontinuitet af koronare lumen 1-4. For at undgå disse komplikationer, vil en lovende strategi være at dække den vaskulære overflade i angioplastik site, som potentielt vil hæmme restenose, mindske risici fra diskontinuitet af fartøjets lumen, og forhindre perifer emboli. Tidligere undersøgelser har sammenlignet nøgne metal stents til stentimplantater med positive resultater for stentimplantater 5. Forskere har brugt flere materialer til at fremstille membraner til at dække stents. Dette omfatter syntetiske materialer som polyethylentetraphthalat (PET), polytetrafluorethylen (PTFE), polyurethan (PU), og silicium eller autologt kar væv til fremstilling dækket stenter 6-9. En ideel graft materiale, der anvendes til at dække stenten bør tromboresistent, ikke-biodegradable, og bør integrere med indfødte væv uden overdreven spredning og inflammation 10. Implantatmaterialet anvendes til at dække stenten skal også fremme heling af stent-implantatet.
Stentimplantater er almindeligt anvendt til behandling af aorta coarctatio, pseudo-aneurismer af halspulsåren, arteriovenøs fistler, degenereret vene transplantater, og store til giant cerebrale aneurismer. Men udviklingen af små kaliber stentimplantater er begrænset af evnen til at opretholde lav profil og fleksibilitet, som hjælper med indsættelse af de stentimplantater 11-14. PU er en elastomer polymer med god mekanisk styrke, som er et ønsket træk for at opnå en lav profil og god fleksibilitet 15,16. Ud over at have god overdragelsen, bør stentimplantater også fremme hurtig heling og endothelialisering. PU dækket stentimplantater har vist bedre biokompatibilitet og øget endothelialisering 17. Forskere hartidligere forsøgt at endothelialize PU dækket stentimplantater ved podning dem med endotelceller 17. Elektrospinning af PU at skabe nanofiber matrix har vist sig at være en værdifuld teknik til fremstilling af vaskulære transplantater 18,19. Eksistensen af nanofibre, der efterligner arkitekturen i native ekstracellulære matrix er også kendt for at fremme endothelcelleproliferation 20,21. Elektrospinning tillader også kontrol over materialets tykkelse 22. Lille kaliber vaskulære transplantater fremstillet af PU er blevet undersøgt for at fremme heling ved hjælp modifikationer, såsom overfladebelægninger, antikoagulantia, og celleproliferation suppressants. Alle disse ændringer er designet til at mægle vært accept og fremme graft healing 23.
Vores gruppe har udviklet en ballon udvides bare metal stent, der kan implementeres i dyremodeller 24-26. Kombinationen af en elektrospundet polyurethan mesh og en boldoon stent har gjort det muligt for os at generere små kaliber ballon udvides stentimplantater. De fleste af de aktuelt tilgængelige stentimplantater indføres gennem lårarterien under en interventionel procedure, men kun få kommercielle dækket stenter kan indføres 1 fransk størrelse større end den, der kræves for en un-oppustet ballon 27. I denne undersøgelse har vi udviklet et lille kaliber vaskulær stent-implantatet ved indkapsling en ballon stent mellem to lag elektrospundet PU, som kan leveres til en koronararterie anvendelse af et standard 8-9 fransk ledekateter i en perkutan indgrebsprocedure.
Protocol
Representative Results
Discussion
We have developed a fabrication technique for a small caliber stent-graft which can be deployed using a standard percutaneous coronary intervention (PCI) procedure. Stent-grafts currently available are limited in their ability to maintain a low profile and flexibility for deployment. Bare metal stents developed by our group in our previous studies have proven to assist in rapid healing of the stented artery24,26. Various polymers have been electrospun by other groups and polyurethane has been proven biostable …
Disclosures
The authors have nothing to disclose.
Acknowledgements
We would like to thank the Division of Engineering, Mayo Clinic for their technical support. This study was financially supported by European Regional Development Fund – FNUSA-ICRC (No. CZ.1.05/1.100/02.0123), National Institutes of Health (T32 HL007111), American Heart Association Scientist Development Grant (AHA #06-35185N), and The Grainger Innovation Fund – Grainger Foundation.
Materials
| Glass syringe | Air Tite | 7.140-33 | Syringe for spinneret |
| Graduated cylinder 5 mL | Fisher Scientific | 08-552-4G | 5 mL pyrex graduated cylinder about 9mm diameter and 11 cm long |
| High voltage generator | Bertan Accociates, Inc. | 205A-30P | Used to apply voltage difference across spinneret and collector |
| Laboratory mixer with rpm control | Scilogex | SCI-84010201 | Available from various laboratory equipment suppliers |
| Polyurethane | DSM | BioSpan SPU | Biospan Segmented Polyurethane |
| Rubber sheet | McMaster Carr | 1370N11 | Used to insulate syringe during electrospinning |
| Stainless steel mandrel | N/A | N/A | Manufactured |
| Stainless steel needle | Hamilton | 91018 | Used as spinneret in electrospinning |
| Support material | EnvisionTec | B04-HT-DEMOMAT | Biocompatible water soluble material |
| Syringe Pump | Harvard Apparatus | 55-3333 |
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