Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology.

The vascular system is integral for maintaining organ-specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue-engineered constructs and microphysiological on-chip platforms.

Fabrication and Implementation of a Reference-Free Traction Force Microscopy Platform.

Quantifying cell-induced material deformation provides useful information concerning how cells sense and respond to the physical properties of their microenvironment. While many approaches exist for measuring cell-induced material strain, here we provide a methodology for monitoring strain with sub-micron resolution in a reference-free manner. Using a two-photon activated photolithographic patterning process, we demonstrate how to generate mechanically and bio-actively tunable synthetic substrates containing embedded arrays of fluorescent fiducial markers to easily measure three-dimensional (3D) material deformation profiles in response to surface tractions.

Reference-Free Traction Force Microscopy Platform Fabricated via Two-Photon Laser Scanning Lithography Enables Facile Measurement of Cell-Generated Forces.

Cells sense and respond to the physical nature of their microenvironment by mechanically probing their surroundings via cytoskeletal contractions. The material response to these stresses can be measured via traction force microscopy (TFM). Traditional TFM platforms present several limitations including variable spatial resolution, difficulty in attaining the full three-dimensional (3D) deformation/stress profile, and the requirement to remove or relax the cells being measured to determine the zero-stress state.

Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture.

Hematopoietic stem cells (HSCs) have been used therapeutically for decades, yet their widespread clinical use is hampered by the inability to expand HSCs successfully in vitro. In culture, HSCs rapidly differentiate and lose their ability to self-renew. We hypothesize that by mimicking aspects of the bone marrow microenvironment in vitro we can better control the expansion and differentiation of these cells.

Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells.

Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood diseases, but widespread application of HSC therapeutics has been hindered by the limited availability of HSCs. With a better understanding of the HSC microenvironment and the ability to precisely recapitulate its components, we may be able to gain control of HSC behavior. In this work we developed a novel, biomimetic PEG hydrogel material as a substrate for this purpose and tested its potential with an anchorage-independent hematopoietic cell line, 32D clone 3 cells.