Rational design of multi-compartmentalized µMESH implants for the treatment of brain disorders

Despite advances in targeted therapies, the survival rate for glioblastoma (GBM) patients has not improved over the past 20 years. The efficacy of GBM treatment remains constrained by non-specific distribution, tumor heterogeneity, and a highly immunosuppressive microenvironment. An innovative drug delivery system – µMESH – has recently been developed to address these challenges. This platform consists of a flexible, biodegradable, dual-compartment polymeric film, and previous results have demonstrated its ability to support locoregional therapies. A variety of polymer combinations, including polyvinyl alcohol (PVA) and poly(lactic-co-glycolic acid) (PLGA), have been explored for their ability to encapsulate and deliver therapeutics, as well as for their physical, chemical, and mechanical properties. The research presented in this thesis aims to maximize the therapeutic potential of µMESH by optimizing drug loading strategies and efficiency, expanding targeted multi-therapy applications, and fine-tuning release properties through adjustments in geometry, mechanical parameters, and biomaterial composition. The versatility of µMESH lies in its ability to be tailored to specific clinical needs, allowing for precise control over therapeutic cargo, material composition, and structural properties. Notably, in GBM mouse model, a single deposition of µMESH significantly extended survival rates compared to systemic treatments or other local therapies. These findings provide a strong foundation for further exploration of µMESH-based therapies.