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An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

Verbrugghe P, Verhoeven J, Coudyzer W, Verbeken E, Dubruel P, Mendes E, Stam F, Meuris B, Herijgers P - J Mater Sci Mater Med (2015)

Bottom Line: Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation.Indirect and direct testing of the material gave no indication of the haemolytic effects of the material.Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Surgery, UZ Leuven, Herestraat 49, 3000, Louvain, Belgium. peter.verbrugghe@uzleuven.be.

ABSTRACT
There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery).

No MeSH data available.


Related in: MedlinePlus

Average blood values, with standard deviation, 0 days (white), 14 days (grey), and 28 days (dark grey) after implantation
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Fig4: Average blood values, with standard deviation, 0 days (white), 14 days (grey), and 28 days (dark grey) after implantation

Mentions: The average flow in the carotid artery before occlusion was 248 ± 4 ml/min. One hour after hydrogel implantation, flow was zero in all three sheep. Perioperative angiography confirmed this finding. Doppler flow measurements and angiography (Fig. 3) 4 weeks later showed a persistent occlusion. At that time some filling defect and decrease in vessel diameter was visible proximal to the hydrogel. Evaluation of the pressure directly after implantation showed a slightly lower pressure distal from the hydrogel (mean pressure: 65 ± 16 mmHg) compared to the proximal pressure (mean pressure: 74 ± 21 mmHg). Four weeks after implantation the difference in mean arterial pressure in front and behind the hydrogel is still measurable, 74 ± 17 and 62 ± 14 mmHg, respectively. Daily evaluation showed no evidence of any health problems in any off the sheep. There were no signs of organ failure, stroke or infection. Blood sample evaluation (Fig. 4) gave normal values throughout the experiment. Ion concentrations were normal. There were no indications of haemolysis, as lactate dehydrogenase (LDH) and plasma haemoglobin levels were normal. No indication of kidney failure either as urea and creatinin were low. There was also no evidence of cholestatic liver disease; bilirubin levels were below 0.18 mg/dL. All blood cell counts were normal, without any sign of inflammation and the number of white blood cells (WBC) being low. Furthermore, cerebral evaluation by an experienced radiologist did not show any sign of cerebral infarction caused by embolization.Fig. 3


An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

Verbrugghe P, Verhoeven J, Coudyzer W, Verbeken E, Dubruel P, Mendes E, Stam F, Meuris B, Herijgers P - J Mater Sci Mater Med (2015)

Average blood values, with standard deviation, 0 days (white), 14 days (grey), and 28 days (dark grey) after implantation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608972&req=5

Fig4: Average blood values, with standard deviation, 0 days (white), 14 days (grey), and 28 days (dark grey) after implantation
Mentions: The average flow in the carotid artery before occlusion was 248 ± 4 ml/min. One hour after hydrogel implantation, flow was zero in all three sheep. Perioperative angiography confirmed this finding. Doppler flow measurements and angiography (Fig. 3) 4 weeks later showed a persistent occlusion. At that time some filling defect and decrease in vessel diameter was visible proximal to the hydrogel. Evaluation of the pressure directly after implantation showed a slightly lower pressure distal from the hydrogel (mean pressure: 65 ± 16 mmHg) compared to the proximal pressure (mean pressure: 74 ± 21 mmHg). Four weeks after implantation the difference in mean arterial pressure in front and behind the hydrogel is still measurable, 74 ± 17 and 62 ± 14 mmHg, respectively. Daily evaluation showed no evidence of any health problems in any off the sheep. There were no signs of organ failure, stroke or infection. Blood sample evaluation (Fig. 4) gave normal values throughout the experiment. Ion concentrations were normal. There were no indications of haemolysis, as lactate dehydrogenase (LDH) and plasma haemoglobin levels were normal. No indication of kidney failure either as urea and creatinin were low. There was also no evidence of cholestatic liver disease; bilirubin levels were below 0.18 mg/dL. All blood cell counts were normal, without any sign of inflammation and the number of white blood cells (WBC) being low. Furthermore, cerebral evaluation by an experienced radiologist did not show any sign of cerebral infarction caused by embolization.Fig. 3

Bottom Line: Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation.Indirect and direct testing of the material gave no indication of the haemolytic effects of the material.Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiac Surgery, UZ Leuven, Herestraat 49, 3000, Louvain, Belgium. peter.verbrugghe@uzleuven.be.

ABSTRACT
There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery).

No MeSH data available.


Related in: MedlinePlus