Synthetic poly(ethylene glycol) (PEG) hydrogels can be engineered to provide cells with precisely defined biochemical and biophysical signals. Designing cell-instructive hydrogels has been a major focus within the biomaterials community, and there is now a strong interest in incorporating stimulus responsive elements that allow for user-directed manipulation of the cellular microenvironment. Photochemical reactions are particularly attractive for this purpose as they provide an excellent means with which to achieve precise spatio-temporal control over the presentation of biological signals. In my research I am exploiting multiple photo-chemistries to develop advanced hydrogel platforms that allow for photo-activation of “caged” biomolecule signals (see figure), modulation of hydrogel crosslinking, and photo-release of soluble factors. In addition, to increase the versatility of these photo-responsive hydrogels, a second theme in my research is the implementation of orthogonal “click” reactions for hydrogel crosslinking (e.g., Cu catalyzed azide-alkyne cycloaddition). Ultimately, the materials we are developing will provide powerful tools with which to interrogate the effects of microenvironmental cues on cells and also to direct complex cell functions like cell attachment, migration, and differentiation.
An inactive “caged” biomolecule can be photo-activated with an appropriate wavelength of light to produce the desired bioactive molecule. The fluorescent image demonstrates uncaging of a cell-adhesive RGD peptide within a 3D hydrogel using two-photon irradiation. The uncaged regions appear darker due to a loss of fluorescence.
M.A. Azagarasamy, D.L. Alge, Radhakrishnan S., Tibbitt M.W., and K.S. Anseth. Photocontrolled nanoparticles for on-demand release of proteins. Biomacromolecules, 2012 Aug; 13(8): 2219-24.
D.L. Alge, T. Treasure, J. Bennet, S. Voytik-Harbin, W.S. Goebel and T-M G. Chu. Poly(propylene fumarate) reinforced dicalcium phosphate dihydrate cement composites for bone tissue engineering. Journal of Biomedical Materials Research Part A, 2012 Jul; 100(7): 1792-802.
D.L. Alge and T-M G. Chu. In vitro degradation and biocompatibility of cements prepared with the MCPM/HA system reveals that conversion to HA is a key degradation mechanism. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2012 Apr; 100(3): 595-602.
D.L. Alge and T-M G. Chu. Calcium phosphate cement reinforcement by polymer infiltration and in situ curing: a method for 3D scaffold reinforcement. Journal of Biomedical Materials Research Part A, 2010 Aug; 94(2): 547-55.
D.L. Alge, D. Zhou, L.L. Adams, B.K. Wyss, M.D. Shadday, T-M G. Chu, E.J. Woods, W. S. Goebel. Donor-matched comparison of dental pulp stem cells and bone marrow-derived mesenchymal stem cells in a rat model. Journal of Tissue Engineering and Regenerative Medicine, 2010 Jan; 4(1): 73-81.