Physical and chemical cell microenvironment properties have become increasingly recognized as regulators of cellular functions1-4 such as migration, cytoskeletal organization, and differentiation. While advances have been made in the fabrication of materials for cell culture, the properties of these material systems typically are fixed upon formation. In situ control of material properties is needed to study their effect on dynamic cellular processes such as differentiation and migration. Here, we will discuss synthetic approaches for stimuli triggered control of material properties, specifically hydrogel modulus and epitope presentation, via the incorporation of photolytically5, 6 or enzymatically7 cleavable sequences within the gel-forming macromers and resulting hydrogels. Utilizing these materials, we will examine the influence of microenvironment structure on cell function, specifically epithelial cell phenotype and assembly. Incorporation of photolytically or enzymatically degradable sequences within monomers and hydrogels enables the design of unique, dynamic cell culture platforms for exploring how changes in properties influence cell fate.
References
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2. Tibbitt, M.W. & Anseth, K.S. Hydrogels as Extracellular Matrix Mimics for 3D Cell Culture. Biotechnol. Bioeng. 103, 655-663 (2009).
3. Keung, A.J., Kumar, S. & Schaffer, D.V. in Annual Review of Cell and Developmental Biology, Vol 26, Vol. 26 533-556 (Annual Reviews, Palo Alto; 2010).
4. Lin, C.C. & Anseth, K.S. PEG Hydrogels for the Controlled Release of Biomolecules in Regenerative Medicine. Pharm. Res. 26, 631-643 (2009).
5. Kloxin, A.M., Kasko, A.M., Salinas, C.N. & Anseth, K.S. Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties. Science 324, 59-63 (2009).
6. Kloxin, A.M., Tibbitt, M.W. & Anseth, K.S. Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms. Nat. Protoc. 5, 1867-1887 (2010).
7. Fairbanks, B.D. et al. A versatile synthetic extracellular matrix mimic via thiol-norbornene photopolymerization. Adv. Mater. 21, 5005-5010 (2009).
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