NeuroSigma (United States)

Electrostatic endothelial cell seeding has evolved as an exceptional technique to improve the efficiency of cell seeding in terms of frequency of attached cells and the amount of cell adhesion for the treatment of vascular diseases. In the recent times, both untreated and superhydrophilic thin film nitinol (TFN) have exhibited strong prospects as substrates for creation of small-diameter endovascular grafts due to their hallmark properties of superelasticity, ultra low-profile character, and grown hemocompatible oxide layer with the presence of a uniform endothelial layer on the surface. The purpose of the current study is to understand the effects of endothelial cell seeding parameters (i.e., applied voltage, incubation time, substrate chemistry, and cell suspension solution) to investigate the cell seeding phenomenon and to improve the cell adhesion and growth on the TFN surface under electrostatic transplantation. Both parallel plate and cylindrical capacitor models were used along with the Taguchi Design of Experiment (DOE) methods to design in vitro test parameters. A novel in vitro system for a cylindrical capacitor model was created using a micro flow pump, micro incubation system, and silicone tubings. The augmented endothelialization on thin film nitinol was developed to determine the effect of cell seeding and deployed in a 6 Fr intravascular catheter setup. Cell viability along with morphology and proliferation of adhered cells were evaluated using fluorescent and scanning electron microscopy. Our results demonstrated that the maximum number of cells attached on STFN in the catheter was observed in 5 V with the 2 h exposure of in the cell culture medium (CCM) solution. The condition showed 5 V voltage with 0.68 × 10−6 µC electrostatic charge and 5.11 V·mm−1 electric field. Our findings have first demonstrated that the electrostatic endothelialization on the superhydrophilic thin film nitinol endograft within the catheter prior to the endovascular procedure could enhance the biocompatibility for low-profile endovascular applications.

Electrostatic endothelial cell seeding has evolved as an exceptional technique to improve the efficiency of cell seeding in terms of frequency of attached cells and the amount of cell adhesion for the treatment of vascular diseases. In the recent times, both untreated and superhydrophilic thin film nitinol (TFN) have exhibited strong prospect as substrates for creation of small-diameter endovascular grafts due to their hallmark properties of superelasticity, ultra low-profile character, grown hemocompatible oxide layer with the presence of a uniform endothelial layer on the surface. The purpose of the current study is to understand the effects of endothelial cell seeding parameters (i.e., applied voltage, incubation time, substrate chemistry and cell suspension solution) to investigate the cell seeding phenomenon and to improve the cell adhesion and growth on the TFN surface under electrostatic transplantation. Both parallel plate and cylindrical capacitor models were used along with the Taguchi Design of Experiment (DOE) methods to design in vitro test parameters. A novel in vitro system for cylindrical capacitor model was created using a micro flow pump, micro incubation system, and silicone tubings. The augmented endothelialization on thin film nitinol was developed to determine the effect of cell seeding and deployed in a 6 Fr intravascular catheter setup. Cell viability along with morphology and proliferation of adhered cells were evaluated using fluorescent and scanning electron microscopy. Our results demonstrated that the maximum number of cells attached on STFN in the catheter was observed in 5V with the 2 hr exposure of in the cell culture medium (CCM) solution. The condition showed 5V voltage with 0.68×10-6 µC electrostatic charge and 5.11 V·mm-1 electric field. Our findings have first demonstrated that the electrostatic endothelialization on the superhydrophilic thin film nitinol endograft within the catheter prior to the endovascular procedure could enhance the biocompatibility for low-profile endovascular applications.

Purpose Thin Film Nitinol can be processed to produce a thin microporous sheet for vascular applications. As compared to current flow diverters constructed as braided tubes, the TFN device has a lower percent metal coverage ( 2 ). We present in vivo results from treatment of experimental rabbit aneurysms using a TFN device. Methods The TFN device was comprised of the TFN sheet supported by a self-expanding, laser-cut nitinol neuro-stent. 21 aneurysms in the rabbit elastase aneurysm model were treated with a single device; devices were also placed over 17 lumbar arteries to model peri-aneurysmal branch arteries of the cranial circulation. Angiography was performed at sacrifice to assess aneurysm occlusion and lumbar artery flow. Gross pathology and en face CD31 immunofluorescent staining was performed on a subset of devices to quantify neck endothelialization. Results One animal died from causes not device related, and in one animal the TFN flow diverter did not cover the aneurysm neck region. Markedly reduced intra-aneurysmal flow was observed on angiography immediately after device placement in all aneurysms. At 2-week follow-up 57% of aneurysms had complete or near complete occlusion ( n = 7 ), and at 4-week ( n = 8 ) and 12-week ( n = 4 ) follow-up 75% of aneurysms had complete or near complete occlusion. All 17 lumbar arteries were patent at follow-up. CD31 staining of aneurysms treated with the TFN flow diverter ( n = 6 , avg. implant duration 6.3 weeks, avg. neck area of 6.26 mm 2 ) showed that 75 ± 16% of the aneurysm neck region was endothelialized at the time of sacrifice. Conclusions Results from pre-clinical testing of a TFN flow-diverter are encouraging. Marked reductions in intra-aneurysmal flow were observed acutely in all aneurysms treated and there was a 75% rate of complete or near-complete occlusion at 4 and 12-week follow-up. All lumbar arteries treated with the device were patent acutely and at follow-up. Results from CD31 staining suggest that the TFN mesh serves not only as a physical barrier to reduce intra-aneurysmal flow, but also as a biological scaffold that may facilitate rapid tissue in-growth and aneurysm neck healing. Disclosures D. Kallmes: None. R. Kadirvel: None. Y. Ding: None. D. Dai: None. C. Kealey: 1; C; NeuroSigma, Inc., V. Gupta: 1; C; NeuroSigma, Inc., D. Johnson: 1; C; NeuroSigma.