Applicability of Drug Response Metrics for Cancer Studies using Biomaterials

Bioengineers have built models of the tumour microenvironment (TME) in which to study cell–cell interactions, mechanisms of cancer growth and metastasis, and to test new therapies. These models allow researchers to culture cells in conditions that include features of the in vivo TME implicated in regulating cancer progression, such as extracellular matrix (ECM) stiffness, integrin binding to the ECM, immune and stromal cells, growth factor and cytokine depots, and a three-dimensional geometry more representative of the in vivo TME than tissue culture polystyrene (TCPS). These biomaterials could be particularly useful for drug screening applications to make better predictions of efficacy, offering better translation to preclinical models and clinical trials. However, it can be challenging to compare drug response reports across different biomaterial platforms in the current literature. This is, in part, a result of inconsistent reporting and improper use of drug response metrics, and vast differences in cell growth rates across a large variety of biomaterial designs. This study attempts to clarify the definitions of drug response measurements used in the field, and presents examples in which these measurements can and cannot be applied. We suggest as best practice to measure the growth rate of cells in the absence of drug, and follow our ‘decision tree’ when reporting drug response metrics

Perspective on Translating Biomaterials Into Glioma Therapy: Lessons From in Vitro Models

Glioblastoma (GBM) is the most common and malignant form of brain cancer. Even with aggressive standard of care, GBM almost always recurs because its diffuse, infiltrative nature makes these tumors difficult to treat. The use of biomaterials is one strategy that has been, and is being, employed to study and overcome recurrence. Biomaterials have been used in GBM in two ways: in vitro as mediums in which to model the tumor microenvironment, and in vivo to sustain release of cytotoxic therapeutics. In vitro systems are a useful platform for studying the effects of drugs and tissue-level effectors on tumor cells in a physiologically relevant context. These systems have aided examination of how glioma cells respond to a variety of natural, synthetic, and semi-synthetic biomaterials with varying substrate properties, biochemical factor presentations, and non-malignant parenchymal cell compositions in both 2D and 3D environments. The current in vivo paradigm is completely different, however. Polymeric implants are simply used to line the post-surgical resection cavities and deliver secondary therapies, offering moderate impacts on survival. Instead, perhaps we can use the data generated from in vitro systems to design novel biomaterial-based treatments for GBM akin to a tissue engineering approach. Here we offer our perspective on the topic, summarizing how biomaterials have been used to identify facets of glioma biology in vitro and discussing the elements that show promise for translating these systems in vivo as new therapies for GBM

Electroactive tissue scaffolds with aligned pores as instructive platforms for biomimetic tissue engineering

Tissues in the body are hierarchically structured composite materials with tissue-specific chemical and topographical properties. Here we report the preparation of tissue scaffolds with macroscopic pores generated via the dissolution of a sacrificial supramolecular polymer-based crystal template (urea) from a biodegradable polymer-based scaffold (polycaprolactone, PCL). Furthermore, we report a method of aligning the supramolecular polymer-based crystals within the PCL, and that the dissolution of the sacrificial urea yields scaffolds with macroscopic pores that are aligned over long, clinically-relevant distances (i.e., centimeter scale). The pores act as topographical cues to which rat Schwann cells respond by aligning with the long axis of the pores. Generation of an interpenetrating network of polypyrrole (PPy) and poly(styrene sulfonate) (PSS) in the scaffolds yields electroactive tissue scaffolds that allow the electrical stimulation of Schwann cells cultured on the scaffolds which increases the production of nerve growth factor (NGF)