In Vitro and In Vivo Evaluation of Nanofiber-Reinforced Thermosensitive Gel for Vascular Embolization

Tuesday, April 1, 2025

3:36 PM – 3:45 PM CT

Location: Music City Center, 201 AB

Presenting Author(s)

Yasushi Kimura, MD, PhD

Project Assistant Professor
Osaka University Graduate School of Medicine, Japan

Author/Co-author(s)

YK

Yuji Koretsune, MD

Clinical Fellow
Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
NK

Norifumi Kennoki, MD, PhD

Specially Appointed Researcher/Fellow
Osaka University Graduate School of Medicine, Japan
YM

Yu Masuda, MD

Medical Staff
Osaka University Graduate School of Medicine, Japan
Hiroki Satomura, MD (he/him/his)

Clinical Fellow
Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
KT

Kosuke Tomotake, MD

Clinical Fellow
Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Japan
HY

Hiroki Yano, n/a

PhD Student
Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Japan
KT

Kaishu Tanaka, n/a

assistant professor
Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Japan
YO

Yusuke Ono, n/a

Assistant Professor
Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Japan
HH

Hiroki Higashihara, n/a

associate professor
Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Japan
nt

noriyuki tomiyama, n/a

professor
Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Japan

Purpose: Poloxamer 407 (PL), a previously reported injectable thermosensitive gel, tends to recanalize soon after embolization due to its erosion characteristics. To address this limitation, we developed a novel Nanofiber-Reinforced Thermosensitive (NRT) gel that offers enhanced mechanical properties for prolonged embolization. This study aimed to develop and evaluate the NRT gel as a potential platform for vascular embolization.

Materials and Methods:

The NRT gel was formulated by combining PL (16% w/v) dissolved in contrast media with two types of nanofibers: 1% cellulose nanofiber (CNF) or 2% silk fibroin (SF). The gels were evaluated for lower critical solution temperature (LCST), viscosity, viscoelasticity, and X-ray visibility. An in vitro embolization efficacy test was performed using a serum flow model with a pulsating pump (30 mL/min, 60 bpm). PL (16% w/v) dissolved in contrast media was used as a control. For the in vivo embolization procedure, a 1.6 Fr. catheter was inserted via the tail artery of anesthetized rats. The right renal artery was embolized with NRT gel containing SF, while the left renal artery was left unembolized. On day 3, the rats were euthanized, and both kidneys were harvested for histopathological analysis. Staining methods included hematoxylin and eosin (H&E) and immunohistochemistry for CD31 and F4/80.

Results:

The LCST of PL and NRT gels (CNF/SF) was 30.5°C and 25.3°C/31.6°C, respectively. NRT gels demonstrated higher viscosity (CNF/SF: 171.3Pa·s/144.8Pa·s vs. PL: 53.2 Pa·s, P < 0.0001) at 20°C and greater storage modulus (CNF/SF: 13.2kPa/11.7kPa vs. PL: 7.5 kPa, P < 0.0001) at 37°C. The NRT gels were also visible under X-ray. In the flow model, PL alone failed to embolize pulsatile flow, whereas NRT gels successfully achieved embolization.
In vivo, the NRT gel containing SF was visible during injection, and no recanalization was observed in post-embolization angiography. The rats remained healthy following the procedure. H&E staining showed renal infarction and ischemic acute tubular necrosis in the embolized kidneys. NRT gel was present in peripheral CD31-positive vessels. F4/80-positive macrophages were observed in the periphery of the infarcted area.

Conclusion:

NRT gels demonstrated superior mechanical properties compared to PL in vitro, and the NRT gel containing SF effectively embolized vessels in vivo without early recanalization.