Development of an Injectable Hydrogel for Histotripsy Ablation Toward Future Glioblastoma Therapy Applications

Area of Science:

• Biomaterials Science
• Oncology
• Neurosurgery

Background:

• Glioblastoma (GBM) is a highly aggressive primary brain tumor with a high recurrence rate.
• Residual GBM cells post-treatment can infiltrate healthy tissue, leading to secondary tumor formation.
• Current treatments struggle to eliminate all infiltrating GBM cells, necessitating novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate an injectable hydrogel for attracting, collecting, and ablating residual GBM cells.
• To assess the feasibility of using histotripsy (focused ultrasound) to ablate hydrogel-encapsulated GBM cells.
• To ensure the hydrogel is compatible with the GBM microenvironment and can be synthesized under relevant conditions.

Main Methods:

• Synthesis of a thiol-Michael addition hydrogel optimized for GBM microenvironment compatibility.
• In vitro assessment of hydrogel synthesis mimicking GBM resection cavities.
• Evaluation of ultrasound imaging for distinguishing hydrogel from brain tissue.
• Application of histotripsy using a 500 kHz transducer to ablate encapsulated cells.

Main Results:

• Hydrogel synthesis was bio-orthogonal, scalable, and not shear-thinning.
• Ultrasound imaging successfully differentiated the hydrogel from porcine brain tissue.
• Histotripsy generated precise bubble clouds, enabling uniform ablation and mechanical fractionation of encapsulated red blood cells (as a model for GBM cells).

Conclusions:

• The developed injectable hydrogel is a promising platform for biomaterials-based glioblastoma treatment.
• The hydrogel effectively attracts and entraps cells, and histotripsy provides a method for their ablation.
• This approach offers a potential strategy to mitigate GBM recurrence after surgical resection.