title: Modular and Adaptable Tumor Niche Prepared from Visible Light Initiated Thiol-Norbornene Photopolymerization.
abstract: Photopolymerized biomimetic hydrogels with adaptable properties have been widely used for cell and tissue engineering applications. As a widely adopted gel cross-linking method, photopolymerization provides experimenters on-demand and spatial-temporal controls in gelation kinetics. Long wavelength ultraviolet (UV) light initiated photopolymerization is among the most popular methods in the fabrication of cell-laden hydrogels owing to its rapid and relatively mild gelation conditions. The use of UV light, however, still causes concerns regarding its potential negative impacts on cells. Alternatively, visible light based photopolymerization can be used to cross-link cell-laden hydrogels. The majority of visible light based gelation schemes involve photoinitiator, co-initiator, and comonomer. This multicomponent initiation system creates added challenges for optimizing hydrogel formulations. Here, we report a co-initiator/comonomer-free visible light initiated thiol-norbornene photopolymerization scheme to prepare modular biomimetic hydrogels suitable for in situ cell encapsulation. Eosin-Y was used as the sole initiator to initiate modular gelation between synthetic macromers (e.g., thiolated poly(vinyl alcohol) or poly(ethylene glycol)) and functionalized extracellular matrices (ECMs) including norbornene-functionalized gelatin (GelNB) or thiolated hyaluronic acid (THA). These components are modularly cross-linked to afford bioinert (i.e., purely synthetic), bioactive (i.e., using gelatin), and biomimetic (i.e., using gelatin and hyaluronic acid) hydrogels. The stiffness of the hydrogels can be easily tuned without affecting the contents of the bioactive components. Furthermore, the use of naturally derived biomacromolecules (e.g., gelatin and HA) renders these hydrogels susceptible to enzyme-mediated degradation. In addition to demonstrating efficient and tunable visible light mediated gelation, we also utilized this biomimetic modular gelation system to formulate artificial tumor niche and to study the effects of cell density and gel modulus on the formation of pancreatic ductal adenocarcinoma (PDAC) spheroids.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Han
authors.initials: H
authors.lastname: Shih
authors.affiliation: Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis , Indianapolis, Indiana 46202, United States.
authors.forename: Tanja
authors.initials: T
authors.lastname: Greene
authors.affiliation: Department of Medicine and Biochemistry & Molecular Biology, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, United States.
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis , Indianapolis, Indiana 46202, United States.|Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202, United States.
authors.forename: Chien-Chi
authors.initials: CC
authors.lastname: Lin
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D002452:Cell Count; D002470:Cell Survival; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008027:Light; D009636:Norbornanes / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D058105:Polymerization; D018874:Spheroids, Cellular / Q000473:pathology*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D023822:Tissue Engineering; D014407:Tumor Cells, Cultured
chemical_list: D003432:Cross-Linking Reagents; D020100:Hydrogels; D009636:Norbornanes; D013438:Sulfhydryl Compounds; C046060:2-norbornene