Outline

Problem

Current treatments for glioblastoma multiforme are limited to palliative measures. The diffusive nature of glioblastoma cells promotes a recurrent tumor which, in more than 90% of cases, develops immediately adjacent to the resection margin or within several centimeters of the resection cavity [Journal of Clinical Oncology]. Patients are subject to several resection procedures, suggesting a reason for the lack in the practice of filling voids with biomaterials.


Current Methods

Several experimental treatments have been conducted. In one instance, hyaluronic acid-poly-D-lysine-based three dimensional hydrogel has been implanted in the void. The hydrogel composition is determined to mimic the conditions of the ECM, which contains high concentrations of hyaluronic acid. In addition to providing a biocompatible matrix, the acid used in conjunction with poly-D-lysine, creates a matrix with a porous microstructure from the cross-linking of HA and PDL. The matrix is implanted to serve as a scaffold to elicit cell regeneration and to bridge the gap in neural tissue [HA PLD 3D Hydrogel]. The positive charge on PLD has been suggested to promote cell adhesion, assisting in cell regeneration.

Research is currently being conducted to halt the migration of malignant gliomas. Research is directed in elucidating the signal pathway of glioma migration and interfering with the pathway by protein modification. Studies have shown that monoclonal antibodies directed against the α3β1 integrin reduces the level of tumor astrocyte migration on laminin [Journal of Clinical Oncology]. Studies have identified the combination of adhesion, invasion, and motility in causing glioma migration, all of which serve as sources from which the suppression of glioma migration and proliferation can be targeted.

Possible Materials/Solutions

Potential design strategies
- From the investigation in HA-PDL hydrogel matrix, it has been noted that the use of positively charged biomaterials promotes cell adhesion.
- Freeze drying a hydrogel with water as the poring agent promotes the formation of a porous structure
- Incorporation of tumor suppression with scaffold for regeneration
o E.g. coating the scaffold with molecules targeted to interfere with tumor migration pathway.
o Implantation of the scaffold itself serves only as a palliative treatment to limit pain and improve quality of life.


Define Improvement

Performance Testing

- Degradability: exposing of matrix to cytosolic conditions – relatively high pH
- SEM analysis – to observe the performance of the matrix as a scaffold – the migration and adhesion of cells can be observed
- Rheological Analysis – to compare the mechanical properties of the matrix with those of the ECM – similar mechanical properties limits undue stress at the matrix-brain interface

Economics