Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations.

Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease mechanisms are only partially understood. Human model systems complement animal models for both hypothesis testing and drug evaluation to improve the identification of therapeutics relevant to human disease. Despite advances, a challenge remains in understanding the dynamics of human fibroblast responses to complex microenvironment stimuli, motivating the need for more advanced tools to investigate fibrotic mechanisms.

Cell therapy biomanufacturing: integrating biomaterial and flow-based membrane technologies for production of engineered T-cells.

Adoptive T-cell therapies (ATCTs) are increasingly important for the treatment of cancer, where patient immune cells are engineered to target and eradicate diseased cells. The biomanufacturing of ATCTs involves a series of time-intensive, lab-scale steps, including isolation, activation, genetic modification, and expansion of a patient's T-cells prior to achieving a final product. Innovative modular technologies are needed to produce cell therapies at improved scale and enhanced efficacy.

Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects.

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g.

Bridging 2D and 3D culture: probing impact of extracellular environment on fibroblast activation in layered hydrogels.

Many cell behaviors are significantly affected by cell culture geometry, though it remains unclear which geometry from two- to three-dimensional (2D to 3D) culture is appropriate for probing a specific cell function and mimicking native microenvironments. Toward addressing this, we established a 2.5D culture geometry, enabling initial cell spreading while reducing polarization to bridge between 2D and 3D geometries, and examined the responses of wound healing cells, human pulmonary fibroblasts, within it.

Tools for probing host-bacteria interactions in the gut microenvironment: From molecular to cellular levels.

Healthy function of the gut microenvironment is dependent on complex interactions between the bacteria of the microbiome, epithelial and immune (host) cells, and the surrounding tissue. Misregulation of these interactions is implicated in disease. A range of tools have been developed to study these interactions, from mechanistic studies to therapeutic evaluation.

Self-healing boronic acid-based hydrogels for 3D co-cultures.

Synthetic hydrogels have been widely adopted as well-defined matrices for three-dimensional (3D) cell culture, with increasing interest in systems that enable the co-culture of multiple cell types for probing both cell-matrix and cell-cell interactions in studies of tissue regeneration and disease. We hypothesized that the unique dynamic covalent chemistry of self-healing hydrogels could be harnessed for not only the encapsulation and culture of human cells but also the subsequent construction of layered hydrogels for 3D co-cultures. To test this, we formed hydrogels using boronic acid-functionalized polymers and demonstrated their self-healing in the presence of physiologically-relevant cell culture media.