title: Rapid generation of biologically relevant hydrogels containing long-range chemical gradients.
abstract: Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here we describe a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel. The formation of chemical gradient was initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient was spatially controlled by the backward flow time and the hydrogel material containing the gradient was synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), was incorporated in the poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attached and spread along the hydrogel material in a manner consistent with the RGDS gradient profile. A hydrogel containing PEG-DA concentration gradient and constant RGDS concentration was also generated. The morphology of cells cultured on such hydrogel changed from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell-material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; State Key Laboratory of Manufacturing Systems Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: He
authors.forename: Yanan
authors.initials: Y
authors.lastname: Du
authors.forename: Jose L
authors.initials: JL
authors.lastname: Villa-Uribe
authors.forename: Changmo
authors.initials: C
authors.lastname: Hwang
authors.forename: Dichen
authors.initials: D
authors.lastname: Li
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini