Understanding tumor-stroma crosstalk in pancreatic ductal adenocarcinoma (PDAC) is challenged by a lack of stroma-mimicking model systems. To design appropriate models, pancreatic tissue must be characterized with a method capable of evaluating in vitro models as well. Our indentation-based characterization tool quantified the distinct viscoelastic signatures of inflamed resections from pancreatitis, tumors from PDAC, and otherwise normal tissue to inform development of mechanically appropriate engineered tissues and scaffolds. We also made progress toward a 3D in vitro system that recapitulates mechanical properties of tumors. Our in vitro model of stromal cells in collagen and complementary characterization system can be used to investigate mechanisms of cancer-stroma crosstalk in PDAC and to propose and test innovative therapies.

Regenerative medicine and tissue engineering are hindered by the lack of consistent measurements and standards for the mechanical characterization of tissue and scaffolds. Indentation methods for soft matter are favored because of their compatibility with small, arbitrarily shaped samples, but contact mechanics models required to interpret data are often inappropriate for soft, viscous materials. In this study, we demonstrate indentation experiments on a variety of human biopsies, animal tissue, and engineered scaffolds, and we explore the complexities of fitting analytical models to these data. Although objections exist to using Hertz contact models for soft, viscoelastic biological materials since soft matter violates their original assumptions, we demonstrate the experimental conditions that enable consistency and comparability (regardless of arguable misappropriation). Appropriate experimental conditions involving sample hydration, the indentation depth, and the ratio of the probe size to sample thickness enable repeatable metrics that are valuable when comparing synthetic scaffolds and host tissue, and bounds on these parameters are carefully described and discussed. We have also identified a reliable quasistatic parameter that can be derived from indentation data to help researchers compare results across materials and experiments. Although Hertz contact mechanics and linear viscoelastic models may constitute oversimplification for biological materials, the reporting of such simple metrics alongside more complex models is expected to support researchers in tissue engineering and regenerative medicine by providing consistency across efforts to characterize soft matter.