GliaTrap is a biodegradable, non-swelling and non-inflammatory hydrogel with tuned release of CXCL12 to attract migrating glioblastoma cells.

in Scientific reports by Yusuke Suita, Saradha Miriyala, Deniz Merih-Toruner, Mattia Pizzagalli, Owen P Leary, Weizhou Yue, Lingxiao Xie, Blessing Akobundu, Nathan Pertsch, Andras Fiser, Eduardo Fajardo, Jie Shen, Nikos Tapinos

TLDR

  • The study developed a non-swelling, non-inflammatory biomimetic hydrogel that can deliver a chemoattractant for glioblastoma cells and showed its efficacy in attracting invading glioblastoma cells in orthotopic models of human glioblastoma.
  • The study paves the way for the development of a new treatment approach for glioblastoma by using biomimetic hydrogels to target glioblastoma cells.

Abstract

A significant factor in relapse and dismal prognosis of glioblastoma is the migrating glioblastoma cells, which diffuse away from the tumor mass into the brain parenchyma. Post-resection application of biomaterials to deliver cytotoxic agents against the invading glioblastoma cells has recently gained attention. The aim of this study was to develop a non-swelling, non-inflammatory biomimetic hydrogel with sustained release of a chemoattractant for glioblastoma cells and perform in vivo proof-of-concept studies to show chemoattraction of invading glioblastoma cells in orthotopic models of human glioblastoma. We used hyaluronic/collagen II-based (HA/Col) hydrogel that incorporates liposomes loaded with CXCL12 to develop GliaTrap. Sustained release of CXCL12 was measured with an ELISA assay. The non-inflammatory properties of GliaTrap were assessed in-vivo after stereotactic implantation in the mouse brain using a cytokine array and immunohistochemistry. The efficacy of GliaTrap on attracting GSCs was determined in-vivo employing 3D light-sheet microscopy on orthotopic human glioblastoma xenografts. We show that GliaTrap is an injectable, non-swelling biomimetic hydrogel that attains sustained release of CXCL12 and does not induce inflammation in the mouse brain. GliaTrap significantly attracts invading glioblastoma cells in orthotopic xenograft models of human glioblastoma as shown with 3D light sheet microscopy. Our findings indicate that GliaTrap can be safely used to attract invading glioblastoma cells by sustained release of a chemoattractant without inducing inflammatory conditions in the brain or local swelling.

Overview

  • The study aimed to develop a non-swelling, non-inflammatory biomimetic hydrogel that can deliver a chemoattractant for glioblastoma cells and assess its efficacy in attracting invading glioblastoma cells in orthotopic models of human glioblastoma.
  • The study used hyaluronic/collagen II-based (HA/Col) hydrogel that incorporates liposomes loaded with CXCL12 to develop GliaTrap, a sustained release hydrogel system.
  • The study demonstrated the safety and efficacy of GliaTrap in attracting invading glioblastoma cells without inducing inflammatory conditions in the brain or local swelling.

Comparative Analysis & Findings

  • The study found that GliaTrap is an injectable, non-swelling biomimetic hydrogel that attains sustained release of CXCL12.
  • The study used ELISA assay to measure sustained release of CXCL12 from GliaTrap and found that it releases CXCL12 for up to 14 days.
  • The study used 3D light-sheet microscopy to evaluate the efficacy of GliaTrap in attracting GSCs in orthotopic human glioblastoma xenografts and found that GliaTrap significantly attracts invading glioblastoma cells.

Implications and Future Directions

  • The study's findings suggest that GliaTrap can be safely used to attract invading glioblastoma cells by sustained release of a chemoattractant without inducing inflammatory conditions in the brain or local swelling.
  • Future studies should investigate the long-term efficacy and safety of GliaTrap in animal models and explore the possibility of using GliaTrap in combination with other therapies for glioblastoma treatment.
  • The study's results also highlight the potential of biomimetic hydrogels as a platform technology for the delivery of therapeutics to target glioblastoma cells, which can be explored further in future research.
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