Injectable, Dual-Cross-Linked, Dynamic Hydrogel for Tissue Separation and Thermal Shielding during Percutaneous...

To develop a biocompatible hydrogel for hydrodissection to facilitate percutaneous cryoablation.

A hydrogel was created by cross-linking alginate, calcium ions, and polyethylene glycol conjugated with boronic acid. Stability of the gel and maintenance of structural integrity were assessed utilizing serum-containing cell culture media. Mechanical properties of the hydrogel were studied using rheometric analysis, and insulation was assessed during repeat freeze-thaw cycles. Cytotoxicity was examined through direct and indirect contact tests using human fibroblasts. Cytokine tumor necrosis factor-α (TNF-α) release from mouse macrophages was measured as a surrogate for inflammatory effects. Tissue displacement, migration, and resorption of the hydrogel were explored following intraperitoneal instillation in mice using serial ultrasound (US) and magnetic resonance (MR) imaging.

The hydrogel exhibited shear-thinning behavior upon injection and self-healing properties upon repeated mechanical manipulation. Additionally, the gel maintained its insulative properties during consecutive freeze-thaw cycles. Viability of human fibroblasts was similar when cultured with and without the hydrogel for 3 days (100% vs 92%, P = .65). In addition, TNF-α secretion from macrophages in the presence of the gel (123.8 pg/mL [SD ± 99.4]) was comparable to a no-treatment control (47.5 pg/mL [SD ± 15.6], P = .98). Gel injection into the mouse peritoneum achieved durable bowel displacement for 6 hours. Half of the gel remained at 24 hours, with nearly all the gel (95%) resorbed by 72 hours.

This novel hydrogel demonstrated favorable biocompatibility and physical properties for achieving prolonged tissue separation and thermal shielding during cryoablation.