Development and preclinical testing of a novel biodegradable hydrogel vaginal packing technology for gynecologic high-dose-rate brachytherapy

Abstract

Purpose: We evaluated the performance of a novel hydrogel-based strategy developed for clinical use as vaginal packing using phantoms and cadavers, and to compare the hydrogel to gauze and balloon packing.

Material and methods: The biocompatible hydrogel is based on a thiol-Michael addition reaction, with delivery of reagents into the vaginal cavity using a custom-made system. Soft-cured cadavers were used for soft tissue-like mechanical properties. Two cadavers with intact uteri had magnetic resonance imaging (MRI) compatible with tandem and ovoids. For one cadaver, the temperature of the vaginal canal was measured before hydrogel application, during polymerization, and after hydrogel removal. The hydrogel packing and applicator was kept in a second cadaver, which was imaged using computed tomography (CT) and MRI. The hydrogel packing and imaging was repeated for an open multichannel MRI compatible, titanium-based vaginal cylinder placed in a post-hysterectomy cadaver.

Results: The gel reaction occurred within 90 seconds, indicating polymerization at clinical quantities with a 5°C increase in vaginal temperature. CT and MRI imaging identified the hydrogel readily and showed a conformance to anatomy with few air pockets. The entire hydrogel packing was readily retrieved upon completion of imaging.

Conclusions: The novel strategy for polyethylene glycol (PEG)-based hydrogel intra-vaginal packing was able to rapidly polymerize in human cadavers with minimal heat production. Delivery was efficient and able to fill the contours of the vaginal cavity and displace tissue away from the applicator axis. The hydrogel has favorable imaging characteristics on CT and MRI, and shows a potential for clinical use, warranting additional studies for the use in humans.

Keywords: HDR; brachytherapy; cervical cancer; hydrogel; intrauterine tandem; vaginal packing.

Conflict of interest statement

Research reported in this publication was supported by a grant from the Ivy Biomedical Innovation Fund. Dr. Showalter owns equity and is an employee of BrachyFoam, LLC, which is working to develop this technology for commercial use. The authors report no conflict of interest.

Figures

Fig. 1

Hydrogel delivery device. The device consists of (A) two 150 mL syringes (i), attached to silicon tubing to a Y-connector (ii) and a static mixing nozzle (iii). Syringes are held together by a 3D printed clamp to the syringe end and Y-connector (iv), a clamp to the syringe body (v), and a clamp that secures the plungers together for 1 : 1 volume mixing (iv). When fully assembled (B), this design permits delivery of solution A and solution B at 1 : 1 amounts using a clinically relevant quantity of reagents

Fig. 2

A) Phantoms used to simulate vaginal anatomy for testing of hydrogel expansion. B) A cross-sectional view of a phantom displays undulations within the inner lumen of distal portion of the phantom. A coronal computed tomography image (C) demonstrates the expansion of the hydrogel to conform to the undulations within a phantom and wall distention from the polymerization as indicated by the bending of the wall relative to the green line

Fig. 3

Removed multichannel vaginal cylinder with hydrogel intact. The hydrogel product is removed with minimal force of extraction

Fig. 4

Computed tomography (CT) (A) and magnetic resonance imaging (MRI) (B) of T&O with hydrogel packing. The hydrogel results in a homogenous CT signal (A, black arrows) with the get displacing the rectum is (A, white arrow). The polymerized hydrogel results in a homogenous signal well demarcated on T2 MRI from the vaginal mucosa with tissue displacement (B, black arrows)

Fig. 5

Computed tomography (CT) (A) and magnetic resonance imaging (MRI) (B) of 5-channel vaginal brachytherapy applicator with the hydrogel results in a homogenous CT signal (A, black arrows) with the hydrogel displacing the rectum is (A, white arrow). The polymerized hydrogel results in a homogenous signal well distinguished on T2 MRI from the vaginal mucosa (B, black arrows) with displacement of the rectum (B, white arrows)

Fig. 6

Computed tomography (CT) (A) and magnetic resonance imaging (MRI) (B) of T&O with gauze packing. Gauze packing results in significant air pockets (A, black arrows) and areas with unsuccessful displacement of the rectum (A, white arrow) and vaginal tissue (A, gray arrow). T2 MRI imaging further demonstrates area of poor tissue displacement with less than uniform packing (B, white arrow)

Fig. 7

Computed tomography (CT) (A) and magnetic resonance imaging (MRI) (B) of T&O with balloon packing. Balloon packing results in concentrated regions of air pocket (A, black arrows) and areas with partial displacement of the rectum (A, white arrow) and vaginal tissue (A, gray arrow). T2 MRI imaging more clearly demonstrates unequal distribution of the balloon packing (B, black arrows) with areas of poor tissue displacement (B, white arrows)

Fig. 8

Standard vaginal cylinder (A) vs. noval multichannel vaginal cylinder with hydrogel packing (B)