Characterization of Photo-Crosslinked Methacrylated Type I Collagen as a Platform to Investigate the Lymphatic Endothelial Cell Response.

Despite chronic fibrosis occurring in many pathological conditions, few in vitro studies examine how fibrosis impacts lymphatic endothelial cell (LEC) behavior. This study examined stiffening profiles of PhotoCol-commercially available methacrylated type I collagen-photo-crosslinked with the photoinitiators: Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), Irgacure 2959 (IRG), and Ruthenium/Sodium Persulfate (Ru/SPS) prior to evaluating PhotoCol permeability and LEC response to PhotoCol at stiffnesses representing normal and fibrotic tissues. Ru/SPS produced the highest stiffness (~6 kilopascal (kPa)) for photo-crosslinked PhotoCol, but stiffness did not change with burst light exposures (30 and 90 s).

Developing Porous Fibrin Scaffolds with Tunable Anisotropic Features to Direct Myoblast Orientation.

Functional regeneration of anisotropically aligned tissues such as ligaments, microvascular networks, myocardium, or skeletal muscle requires a temporal and spatial series of biochemical and biophysical cues to direct cell functions that promote native tissue regeneration. When these cues are lost during traumatic injuries such as volumetric muscle loss (VML), scar formation occurs, limiting the regenerative capacity of the tissue. Currently, autologous tissue transfer is the gold standard for treating injuries such as VML but can result in adverse outcomes including graft failure, donor site morbidity, and excessive scarring.

Regulating Lymphatic Vasculature in Fibrosis: Understanding the Biology to Improve the Modeling.

Fibrosis occurs in many chronic diseases with lymphatic vascular insufficiency (e.g., kidney disease, tumors, and lymphedema).

Molecular dissection of CRC primary tumors and their matched liver metastases reveals critical role of immune microenvironment, EMT and angiogenesis in cancer metastasis.

Metastasis is the primary cause of cancer mortality. The primary tumors of colorectal cancer (CRC) often metastasize to the liver. In this study, we have collected 122 samples from 45 CRC patients.

Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening.

While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems.

3D collagen fibrillar microstructure guides pancreatic cancer cell phenotype and serves as a critical design parameter for phenotypic models of EMT.

Pancreatic cancer, one of the deadliest cancers, is characterized by high rates of metastasis and intense desmoplasia, both of which are associated with changes in fibrillar type I collagen composition and microstructure. Epithelial to mesenchymal transition (EMT), a critical step of metastasis, also involves a change in extracellular matrix (ECM) context as cells detach from basement membrane (BM) and engage interstitial matrix (IM). The objective of this work was to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to define how ECM composition and biophysical properties modulate pancreatic cancer EMT.

Oligomers modulate interfibril branching and mass transport properties of collagen matrices.

Mass transport within collagen-based matrices is critical to tissue development, repair, and pathogenesis, as well as the design of next-generation tissue engineering strategies. This work shows how collagen precursors, specified by intermolecular cross-link composition, provide independent control of collagen matrix mechanical and transport properties. Collagen matrices were prepared from tissue-extracted monomers or oligomers.

Collagen-polymer guidance of vessel network formation and stabilization by endothelial colony forming cells in vitro.

Vessel morphogenesis is vital to regenerative medicine strategies. Here, collagen polymers, specified by intermolecular cross-link composition, are used to independently vary microstructure (fibril density, interfibril branching) and physical properties (stiffness) to guide 3D vessel network formation by endothelial colony forming cells (ECFC) in vitro. Increasing stiffness, by modulation of fibril density or interfibril branching, increases vessel diameter, length and branching.

Controlled loading and release of a model drug from polypeptide multilayer nanofilms.

A major concern of medicine today is the sustained release of therapeutic compounds. Delivery vehicles for such compounds must be biocompatible. Ideally, loading a drug into the delivery vehicle will be a simple process, and vehicle properties will allow control over the drug release profile under desired conditions.

Stimulated release of small molecules from polyelectrolyte multilayer nanocoatings.

Free thiol-containing polyelectrolytes serve simultaneously as a material for self-assembly of a multilayer nanocoating and as a carrier of small molecules for release from the coating in response to an environmental cue.