Alexander A Oliver, Cem Bilgin, Jonathan Cortese, Esref A Bayraktar, Daying Dai, Yong Hong Ding, Kent D Carlson, Adam J Griebel, Jeremy E Schaffer, Mitchell L Connon, Dan Dragomir-Daescu, Ramanathan Kadirvel, Roger J Guillory, David F Kallmes
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引用次数: 0
Abstract
Introduction: Flow diverters are specialized stents used to treat intracranial aneurysms. Bioresorbable flow diverters (BRFDs) have been proposed as the next-generation of flow diverter technology. BRFDs aim to occlude and heal the aneurysm before safely dissolving into the body, mitigating complications associated with the permanent presence of conventional flow diverters. We previously prototyped BRFDs using an iron-manganese-nitrogen (FeMnN) alloy and demonstrated their flow diversion functionality, radial strength, bioresorbability, and MRI compatibility in benchtop tests. In the current work, we investigated their aneurysm occlusion efficacy in vivo.
Methods: Elastase induced aneurysms were created in seven rabbits and BRFDs were deployed over the aneurysms for 3 months. Aneurysm occlusion efficacy and the biological response was assessed via angiography, gross dissection microscopy, and histology.
Results: The BRFDs failed to occlude the aneurysms in 5/7 rabbits at the 3-month endpoint. The bioresorbable wires appeared to resorb too rapidly and fragment away from the aneurysm neck prior to becoming entirely encased in tissue and completely occluding the aneurysm. In 3/7 rabbits, some FeMnN wires remained over the aneurysm neck that were encased in tissue, partially covering the aneurysm neck. Histological analysis revealed that the wires, when present, were a suitable substrate over which tissue could develop. Therefore, we attribute the poor aneurysm occlusion efficacy to mechanical failure rather than an impaired biological healing response.
Conclusion: The FeMnN BRFDs degraded too rapidly to effectively treat the rabbit elastase induced aneurysms. Future work will focus on developing BRFDs out of materials with a delayed resorption rate.
期刊介绍：
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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