Abstract

Engineering Cryogel Scaffolds to Reconstruct Aspects of the Tumor Microenvironment

Sidi Bencherif, Assistant Professor, Northeastern University

Hypoxia, defined as low oxygen tension, is a characteristic feature of solid tumors and a hallmark of aggressive cancers. Metabolic adaptation to hypoxia leads to tumor cell growth and invasion, resistance to apoptosis, and multi-drug resistance. For decades, a number of solid tumor models have been engineered to emulate key aspects of tumor biology such as hypoxia. However, challenges with tumor formation and reproducibility, inadequate biomechanical cues and 3D microenvironmental features provided to cells, and uncontrolled oxygen depletion among other limitations led to non-physiological tumor cell responses and inaccurate clinical predictions to anti-cancer drugs. To model solid tumors more accurately, we have recently developed an innovative approach using macroporous cryogel scaffolds to induce rapid oxygen depletion while enabling cellular rearrangement into spherical-like cell aggregates within a 3D polymer network. Our preliminary data suggest that our engineered cryogel scaffolds are capable of inducing local hypoxia while promoting tumor cell remodeling and aggressiveness, leading to anti-cancer drug resistance. Tumor-laden cryogels may mimic key aspects of the native tumor microenvironment, making these advanced cellularized scaffolds a promising platform for drug screening and potentially advancing drug development and discovery.