21 FUTURE DEVELOPMENTS AND RESEARCH
Abstract
Novel flow diversion therapies on the horizon are an evolving brainstorm of multifaceted strategies to modify the treatment of cerebrovascular pathologies, generating new therapeutic options for the endovascular community. Favorable experiences within the peripheral world prompted biomechanical advances to facilitate the navigation of the tortuous cervicocerebral vasculature for device delivery. Limited off-label application of covered stents within the cerebrovasculature has shown reduced recanalization rates, creating opportunities for an innovative design tailored to treat specific pathologies. 1 , 2 Polymer coatings may be applied to cover the bare metal of stents, providing corrosion resistance and increased hydrophilicity among other favorable characteristics. Methods of coating and polymer selection are highly scrutinized variables in current research models targeted to promote neoepithelialization, while combating intimal hyperplasia and thrombogenicity. 3 , 4 , 5 Clinical demand to create a flow diversion model averse to thrombotic events, while averting the side effects of dual-antiplatelet therapy required for current models, has driven experimental designs that could potentially preclude the use of antiplatelet therapy. 6 Transitioning to state-of-the-art surface modifications, bioengineers are able to link polymers in a more favorable profile, and electropolish the flow diverter alloys improving their biocompatibility. Concerns of permanent metal constructs piloted the development of bioresorbable vascular scaffolds. Currently being evaluated in the cardiovascular trials, biodegradable vascular stents may have their place in cerebrovascular therapies. 7 , 8 , 9 Ultimately, today′s flow diverters will be supplanted by a more-modern generation that promotes rapid vascular regenesis while providing bioresorbable capabilities with a low thrombogenic profile.
21.1 Introduction
Novel flow diversion therapies on the horizon are an evolving brainstorm of multifaceted strategies to modify the treatment of cerebrovascular pathologies, generating new therapeutic options for the endovascular community. Modifications of flow diversion are currently being tested in some cardiovascular trials with elegant, bioresorbable stent scaffoldings. 8 , 9 Additionally, stent coating alternatives and their method of application to the stent construct, techniques for corrosion prevention, enhanced lubricious coatings for improved delivery, and coating/surface modifications for reduced thrombogenesis are just a small example of current areas of study in the laboratory for improved in vivo tolerability.
21.2 Bioresorbable Stents
Interests in long-term effects of adverse complications associated with permanent metal stents have opened doors to investigation of bioresorbable scaffolds. Vascular tissue bioengineers have worked with multiple substrates, including decellularized constructs, natural polymers, and synthetic polymers. Neovessel generation with epithelialization across the extracellular matrix construct, while preserving mechanical strength of the native vessel, is one hurdle faced when considering in vivo applications. 10 Concern for small-vessel patency continues to be evaluated with experimental research progressing to the achievement of an engineered tissue model of a vascular scaffold suitable for smaller diameter vessels.
21.2.1 Decellularized Vascular Sca ffolds
Laboratory animal models of decellularized vascular scaffolds have shown mixed results with reduced biodegradation rates and biocompatibility issues. The decellularization process can be performed in several different ways (chemical/detergentbased, mechanical abrasion, enzymatic catabolism, etc.), but the ultimate goal of the process is to maintain the extracellular matrix while reducing the immunogenicity of the scaffold. Studies have also attempted adding extracellular matrix components or endothelial progenitor cells to vascular scaffolds to promote rapid endothelialization, that is, human saphenous endothelial cells on a decellularized porcine aorta and hybridization of a polymer scaffold with human allogenic smooth muscle cells. 10 However, none of these models have been utilized in human cerebrovascular trials.
21.2.2 Polymer Vascular Sca ffolds
Nondegradable Polymers
Expanded Teflon, ePTFE, and Dacron, polyethylene terephthalate (PET), have been used as vascular conduits for decades. The patency rate of ePTFE is more favorable due to its electronegative luminal surface, although the patency rate reduces as it is applied to vessels with smaller diameters. 10 While both ePTFE and PET alone have shown poor vascular regenesis, autologous endothelial cells have been harvested and applied with fibrin glue to luminal surfaces of ePTFE grafts with similar long-term patency results as autologous vein grafts. 11
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