Heparin and PEG-based hydrogels to modulate and interrogate dynamic cell behavior

Hydrogel-based biomaterials are often used for biomolecule delivery or encapsulation of cells for tissue engineering and regenerative medicine applications. However, utilizing hydrogels in dynamic cell systems can be challenging, as hydrogels must be engineered to account for changes in cellular behavior. For example, the hydrogel cell culture platforms and analyses techniques employed to investigate cell response to disease conditions should account for variations in cellular communication. In addition, hydrogels used to modulate cellular differentiation, either through protein delivery or direct interactions with cells, should account for evolving cell phenotype. Thus, in this work, hydrogel-based technologies were developed and utilized to interrogate and modulate dynamic cellular behavior. A PEG-based platform was designed and utilized to interrogate MSCs, adipocytes, and osteoblasts under hyperglycemic conditions via multivariate analyses, as these three cell types are implicated in abnormal deposition of marrow adipose tissue and bone in diabetes and osteoporosis. Then, as heparin binds many growth factors involved in cellular differentiation processes, heparin-based MPs were used to temporally modulate endochondral ossification in ATDC5 cells, possibly through heparin-mediated protein sequestration. To further modulate the timing of protein sequestration, heparin-PEG core-shell MPs were designed to enable sequestration and temporally controlled redelivery of protein. Finally, hydrolytically degradable heparin-PEG-based MPs were engineered with tunable heparin content and degradation rate, to enable temporally controlled protein release. Overall, this work demonstrates the ability of PEG and heparin-based hydrogels to investigate and regulate evolving cellular processes.Ph.D