Biomedical subjects

Dirk R Albrecht

Publications and source records attributed to Dirk R Albrecht.

4 recordsLinked to original sources

PubMed2006

Assessment of hepatocellular function within PEG hydrogels.

Tissue-engineered therapies for liver failure offer the potential to augment or replace whole organ transplantation; however, fabrication of hepatic tissue poses unique challenges largely stemming from the complexity of liver structure and function. In this study, we illustrate the utility of highly-tunable, photopolymerizable poly(ethylene glycol) (PEG) hydrogels for 3D encapsulation of hepatic cells and highlight a range of techniques important for examining hepatocellular function in this platform. Owing to our long-term interest in incorporating proliferative progenitor cell types (e.g. hepatoblasts, oval cells, or cells derived from embryonic stem cells) and maintaining the phenotype of differentiated cells, we explored the behavior of bipotential mouse embryonic liver (BMEL) cells as a model progenitor cell and mature, fully differentiated, primary hepatocytes in this biomaterial system. We demonstrated the importance of cell-cell and cell-matrix interactions in the survival and function of these cell types, and the capacity to influence encapsulated cell phenotypes through modulation of hydrogel characteristics or gene silencing. Additionally, we demonstrated imaging techniques critical for the in situ assessment of encapsulated hepatocyte function combined with the ability to control cellular organization and overall architecture through microscale patterning technologies. Further analysis of liver progenitor as well as mature hepatocyte processes within the versatile PEG hydrogel platform will aid in the development of tissue engineered implantable liver systems.

Animals↗

PubMed2006

Probing the role of multicellular organization in three-dimensional microenvironments.

Successful application of living cells in regenerative medicine requires an understanding of how tissue structure relates to organ function. There is growing evidence that presentation of extracellular cues in a three-dimensional (3D) context can fundamentally alter cellular responses. Thus, microenvironment studies that previously were limited to adherent two-dimensional (2D) cultures may not be appropriate for many cell types. Here we present a method for the rapid formation of reproducible, high-resolution 3D cellular structures within a photopolymerizable hydrogel using dielectrophoretic forces. We demonstrate the parallel formation of >20,000 cell clusters of precise size and shape within a thin 2-cm(2) hydrogel and the maintenance of high cell viability and differentiated cell markers over 2 weeks. By modulating cell-cell interactions in 3D clusters, we present the first evidence that microscale tissue organization regulates bovine articular chondrocyte biosynthesis. This platform permits investigation of tissue architecture in other multicellular processes, from embryogenesis to regeneration to tumorigenesis.

Animals↗

PubMed2004

Photo- and electropatterning of hydrogel-encapsulated living cell arrays.

Living cells have the potential to serve as sensors, naturally integrating the response to stimuli to generate predictions about cell fate (e.g., differentiation, migration, proliferation, apoptosis). Miniaturized arrays of living cells further offer the capability to interrogate many cells in parallel and thereby enable high-throughput and/or combinatorial assays. However, the interface between living cells and synthetic chip platforms is a critical one wherein the cellular phenotype must be preserved to generate useful signals. While some cell types retain tissue-specific features on a flat (2-D) surface, it has become increasingly apparent that a 3-D physical environment will be required for others. In this paper, we present two independent methods for creating living cell arrays that are encapsulated within a poly(ethylene glycol)-based hydrogel to create a local 3-D microenvironment. First, 'photopatterning' selectively crosslinks hydrogel microstructures containing living cells with approximately 100 microm feature size. Second, 'electropatterning' utilizes dielectrophoretic forces to position cells within a prepolymer solution prior to crosslinking, forming cell patterns with micron resolution. We further combine these methods to obtain hierarchical control of cell positioning over length scales ranging from microns to centimeters. This level of microenvironmental control should enable the fabrication of next-generation cellular microarrays in which robust 3-D cultures of cells are presented with appropriate physical and chemical cues and, consequently, report on cellular responses that resemble in vivo behavior.

3T3 Cells↗

PubMed2004

Geometric and material determinants of patterning efficiency by dielectrophoresis.

Dielectrophoretic (DEP) forces have been used extensively to manipulate, separate, and localize biological cells and bioparticles via high-gradient electric fields. However, minimization of DEP exposure time is desirable, because of possible untoward effects on cell behavior. Toward this goal, this article investigates the geometric and material determinants of particle patterning kinetics and efficiency. In particular, the time required to achieve a steady-state pattern is theoretically modeled and experimentally validated for a planar, interdigitated bar electrode array energized in a standing-wave configuration. This measure of patterning efficiency is calculated from an improved Fourier series solution of DEP force, in which realistic boundary conditions and a finite chamber height are imposed to reflect typical microfluidic applications. The chamber height, electrode spacing, and fluid viscosity and conductivity are parameters that profoundly affect patterning efficiency, and optimization can reduce electric field exposure by orders of magnitude. Modeling strategies are generalizable to arbitrary electrode design as well as to conditions where DEP force may not act alone to cause particle motion. This improved understanding of DEP patterning kinetics provides a framework for new advances in the development of DEP-based biological devices and assays with minimal perturbation of cell behavior.

Biopolymers↗