STIMULI-RESPONSIVE BIOMATERIALS: ENABLING THE SPATIOTEMPORAL MICROPATTERNING OF PHOTORESPONSIVE HYDROGELS VIA DISULFIDE-BASED LINKERS

Abstract

Photodegradable hydrogels have emerged as a versatile platform for research on tissue engineering, cell function and cell delivery because of the unique property of dynamically altering physical and chemical material properties by the use of light. The ability of modifying extracellular matrix (ECM)-mimicking networks is intriguing as mammalian cells are surrounded by a three-dimensional (3D) environment that is remodeled over time. Frequently, photoresponsive o-nitrobenzyl (oNB) derivatives are incorporated into such networks. Degradation of such hydrogel systems can be either induced by one-photon irradiation using UV light or by a two-photon process applying pulsed IR-laser light. However, the inherent light-sensitivity of the incorporated photo-triggers requires handling under light protection for all experimental steps. Furthermore, high light intensities and irradiation times are necessary for the photoscission that can ultimately damage living cells encapsulated into the material. A striking but rarely used alternative is the utilization of disulfide linkages which become photocleavable by the use of a radical photoinitiator at cytocompatible doses of light. Therefore, we present disulfide building blocks for facile crosslinking of macromers via thiol-ene conjugation. We demonstrate the efficiency of controllable photopolymerization and subsequent photo-erosion of biomaterials via in situ-photorheology and investigated degradation and swelling behavior. The biopolymers used in this study are based on molecularly simple disulfide linkers and modified poly(vinyl alcohol) (PVA) that are assembled by a cytocompatible Michael-type click reaction. Additionally, gelatin was incorporated to form a hybrid biomaterial with adjustable gel stiffness and the ability of two-photon-irradiation mediated micropatterning of disulfide-crosslinked networks.