Outlook and opportunities for engineered environments of breast cancer dormancy.

Dormant, disseminated breast cancer cells resist treatment and may relapse into malignant metastases after decades of quiescence. Identifying how and why these dormant breast cancer cells are triggered into outgrowth is a key unsolved step in treating latent, metastatic breast cancer. However, our understanding of breast cancer dormancy in vivo is limited by technical challenges and ethical concerns with triggering the activation of dormant breast cancer.

Structurally decoupled stiffness and solute transport in multi-arm poly(ethylene glycol) hydrogels.

Synthetic hydrogels are widely used as artificial 3D environments for cell culture, facilitating the controlled study of cell-environment interactions. However, most hydrogels are limited in their ability to represent the physical properties of biological tissues because stiffness and solute transport properties in hydrogels are closely correlated. Resultingly, experimental investigations of cell-environment interactions in hydrogels are confounded by simultaneous changes in multiple physical properties.

Tenascin-C Activation of Lung Fibroblasts in a 3D Synthetic Lung Extracellular Matrix Mimic.

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that match the ECM composition and biomechanics of the lung to study these cell-matrix interactions in vitro.

Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic.

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that contain the ECM composition and biomechanics of the lung to study these cell-matrix interactions .

Solute diffusion and partitioning in multi-arm poly(ethylene glycol) hydrogels.

Controlling solute transport in hydrogels is critical for numerous chemical separation applications, tissue engineering, and drug delivery systems. In previous review work, we have pointed out that proposed theoretical models and associated experiments tend to oversimplify the influence of the hydrogel structure on solute transport by addressing only the effects of the polymer volume fraction and mesh size of the networks on solute transport. Here, we reexamine these models by experimenting with a library of multi-arm poly(ethylene glycol) (PEG) hydrogels with simultaneous variations in four independent structural parameters.

High-Throughput FRAP Analysis of Solute Diffusion in Hydrogels.

Increasingly accurate mathematical models have been developed to relate solute and hydrogel properties to solute diffusion coefficients in hydrogels, primarily by comparing solute sizes and hydrogel mesh sizes. Here, we use a standardized, high-throughput method for fluorescence recovery after photobleaching (FRAP) experiments and analysis to characterize the diffusion coefficients of fluorescein, three sizes of FITC-dextran, and three sizes of FITC-conjugated poly(ethylene glycol) (PEG) through 18 structurally varied poly(vinyl alcohol) (PVA) hydrogel formulations. Increasing the hydrogel mesh radii increased the diffusivities of all the tested solutes within the hydrogels.

Solute Transport Dependence on 3D Geometry of Hydrogel Networks.

Hydrogels are used in drug delivery applications, chromatography, and tissue engineering to control the rate of solute transport based on solute size and hydrogel-solute affinity. Ongoing modeling efforts to quantify the relationship between hydrogel properties, solute properties, and solute transport contribute toward an increasingly efficient hydrogel design process and provide fundamental insight into the mechanisms relating hydrogel structure and function. However, here we clarify previous conclusions regarding the use of mesh size in hydrogel transport models.

Tuning the biomimetic behavior of scaffolds for regenerative medicine through surface modifications.

Tissue engineering and regenerative medicine rely extensively on biomaterial scaffolds to support cell adhesion, proliferation, and differentiation physically and chemically in vitro and in vivo. Changes to the surface characteristics of the scaffolds have the greatest impact on cell response. Here, we discuss five dominant surface modification approaches used to biomimetically improve the most common scaffolds for tissue engineering, those based on aliphatic polyesters.

Dynamic in vitro models for tumor tissue engineering.

Cancer research uses in vitro studies for controllable analysis of tumor behavior and preclinical testing of therapeutics. Shortcomings of basic cell culture systems in recreating in vivo interactions have driven the development of more efficient and biomimetic in vitro environments for cancer research. Assimilation of certain developments in tissue engineering will accelerate and improve the design of these environments.