Publications

@article{Kirkham2020-gg,

title = {Localized induction of gene expression in embryonic stem cell 

 aggregates using holographic optical tweezers to create 

 biochemical gradients},

author = {Glen R Kirkham and James Ware and Thomas Upton and Stephanie Allen and Kevin M Shakesheff and Lee Dk Buttery},

year  = {2020},

date = {2020-01-01},

journal = {Regen. Eng. Transl. Med.},

volume = {6},

number = {3},

pages = {251\textendash261},

publisher = {Springer Science and Business Media LLC},

abstract = {Three-dimensional (3D) cell models that mimic the structure and 

 function of native tissues are enabling more detailed study of 

 physiological and pathological mechanisms in vitro. We have 

 previously demonstrated the ability to build and manipulate 3D 

 multicellular microscopic structures using holographic optical 

 tweezers (HOTs). Here, we show the construction of a precisely 

 patterned 3D microenvironment and biochemical gradient model 

 consisting of mouse embryoid bodies (mEBs) and polymer 

 microparticles loaded with retinoic acid (RA), embedded in a 

 hydrogel. We demonstrate discrete, zonal expression of the 

 RA-inducible protein Stra8 within mEBs in response to release of 

 RA from polymer microparticles, corresponding directly to the 

 defined 3D positioning of the microparticles using HOTs. These 

 results demonstrate the ability of this technology to create 

 chemical microgradients at definable length scales and to 

 elicit, with fidelity and precision, specific biological 

 responses. This technique can be used in the study of in vitro 

 microenvironments to enable new insights on 3D cell models, 

 their cellular assembly, and the delivery of drug or biochemical 

 molecules for engineering and interrogation of functional and 

 morphogenic responses. Graphical abstract.},

keywords = {Embryoid bodies, Embryonic stem cells, HOTs, In vitro model, Optical tweezers, Retinoic acid, Stem cells, Stra 8},

pubstate = {published},

tppubtype = {article}

}