Bioresponsive Hyaluronic Acid-Based Hydrogel Inhibits Matrix Metalloproteinase-2 in Glioblastoma Microenvironment

Glioblastoma multiforme (GBM) is an extremely malignant cancer, resistant to standard therapies. Tumor resection is associated with better outcomes but a complete resection of GBMs is challenging for anatomical limitation and for the high degree of invasiveness. A bioresponsive hydrogel based on hyaluronic acid (HA) cross-linked with a branched metalloproteinase (MMP) inhibitor (MMPI) is proposed. The fully characterized hydrogel, HA-MMPI, presents physical properties suitable for filling the surgical resection cavity and for in situ delivery of the inhibitor. The bioresponsive material selectively inhibits MMP-2 versus MMP-9 in glioblastoma microenvironment.