Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties.

Magnetoactive, -Inspired Hammocks to Probe Lung Epithelial Cell Function.

Introduction: Mechanical forces provide critical biological signals to cells. Within the distal lung, tensile forces act across the basement membrane and epithelial cells atop. Stretching devices have supported studies of mechanical forces in distal lung epithelium to gain mechanistic insights into pulmonary diseases.

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

Human induced pluripotent stem cell (iPSC) derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse-sarcoma derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties.

Integrating mechanical cues with engineered platforms to explore cardiopulmonary development and disease.

Mechanical forces provide critical biological signals to cells during healthy and aberrant organ development as well as during disease processes in adults. Within the cardiopulmonary system, mechanical forces, such as shear, compressive, and tensile forces, act across various length scales, and dysregulated forces are often a leading cause of disease initiation and progression such as in bronchopulmonary dysplasia and cardiomyopathies. Engineered models have supported studies of mechanical forces in a number of tissue and disease-specific contexts, thus enabling new mechanistic insights into cardiopulmonary development and disease.

Programmable Tissue Folding Patterns in Structured Hydrogels.

Folding of mucosal tissues, such as the tissue within the epithelium of the upper respiratory airways, is critical for organ function. Studying the influence of folded tissue patterns on cellular function is challenging mainly due to the lack of suitable cell culture platforms that can recreate dynamic tissue folding in vitro. Here, a bilayer hydrogel folding system, composed of alginate/polyacrylamide double-network (DN) and hyaluronic acid (HA) hydrogels, to generate static folding patterns based on mechanical instabilities, is described.

Silver nanoparticle interactions with glycated and non-glycated human serum albumin mediate toxicity.

Biomolecules bind to and transform nanoparticles, mediating their fate in biological systems. Despite over a decade of research into the protein corona, the role of protein modifications in mediating their interaction with nanomaterials remains poorly understood. In this study, we evaluated how glycation of the most abundant blood protein, human serum albumin (HSA), influences the formation of the protein corona on 40 nm silver nanoparticles (AgNPs) and the toxicity of AgNPs to the HepG2 human liver cell line.

EPIREGULIN creates a developmental niche for spatially organized human intestinal enteroids.

Epithelial organoids derived from intestinal tissue, called enteroids, recapitulate many aspects of the organ in vitro and can be used for biological discovery, personalized medicine, and drug development. Here, we interrogated the cell signaling environment within the developing human intestine to identify niche cues that may be important for epithelial development and homeostasis. We identified an EGF family member, EPIREGULIN (EREG), which is robustly expressed in the developing human crypt.

Silver Nanoparticle Surface Chemistry Determines Interactions with Human Serum Albumin and Cytotoxic Responses in Human Liver Cells.

Engineered nanomaterials (ENMs) are synthesized with a diversity of surface chemistries that mediate biochemical interactions and physiological response to the particles. In this work, silver engineered nanomaterials (AgENMs) are used to evaluate the role of surface charge in protein interactions and cellular cytotoxicity. The most abundant protein in blood, human serum albumin (HSA), was interacted with 40 nm AgENMs with a range of surface-charged coatings: positively charged branched polyethyleneimine (bPEI), negatively charged citrate (CIT), and circumneutral poly(ethylene glycol) (PEG).

Approaches to benchmark and characterize in vitro human model systems.

In vitro human models, such as gastruloids and organoids, are complex three-dimensional (3D) structures often consist of cells from multiple germ layers that possess some attributes of a developing embryo or organ. To use these models to interrogate human development and organogenesis, these 3D models must accurately recapitulate aspects of their in vivo counterparts. Recent advances in single-cell technologies, including sequencing and spatial approaches, have enabled efforts to better understand and directly compare organoids with native tissues.

Microstructured Hydrogels to Guide Self-Assembly and Function of Lung Alveolospheres.

Epithelial cell organoids have increased opportunities to probe questions on tissue development and disease in vitro and for therapeutic cell transplantation. Despite their potential, current protocols to grow these organoids almost exclusively depend on culture within 3D Matrigel, which limits defined culture conditions, introduces animal components, and results in heterogenous organoids (i.e.

Emerging investigator series: characterization of silver and silver nanoparticle interactions with zinc finger peptides.

In biological systems, chemical and physical transformations of engineered silver nanomaterials (AgENMs) are mediated, in part, by proteins and other biomolecules. Metalloprotein interactions with AgENMs are also central in understanding toxicity and antimicrobial and resistance mechanisms. Despite their readily available thiolate and amine ligands, zinc finger (ZF) peptides have thus far escaped study in reaction with AgENMs and their Ag(I) oxidative dissolution product.