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High Resolution Image Download MS PowerPoint Slide Hydrogel-based interfaces continue to attract increasing attention in biomedical applications such as biosensing, tissue engineering, and drug delivery. In this study, dual-functionalizable hydrogels and coatings are fabricated, which can undergo reversible and nonreversible conjugations to yield functional interfaces. In particular, redox-responsive, reversibly functionalizable hydrogels are obtained using photopolymerization of a pyridyl disulfide-containing methacrylate (PDSMA) monomer. An oxanorbornene moiety was incorporated using a furan-protected maleimide-containing methacrylate (FuMaMA) monomer to impart an additional conjugation handle that is stable in a redox environment. While the PDS group enables reversible conjugation with bioactive molecules that are released in a reducing environment, the oxanorbornene unit allows conjugation of tetrazine-containing functional molecules through the inverse electron-demand Diels–Alder (IEDDA) reaction. Hydrogels obtained using photopolymerization were functionalized using thiol-containing fluorescent dye and chemotherapy drug via a thiol-based exchange reaction, followed by their release under reducing conditions. Likewise, nonreversible functionalization of hydrogel is demonstrated using the conjugation of a tetrazine-containing fluorescent dye via the IEDDA reaction. As a therapeutic molecule, doxorubicin (DOX) was reversibly conjugated to these hydrogels by using a disulfide linkage, and redox-responsive release was demonstrated in the presence of glutathione (GSH). Finally, using the dual-functionalization approach, a hydrogel coating containing the cytotoxic drug DOX and cell-targeting peptides was obtained. It is demonstrated that the on-demand release of the cytotoxic drug upon exposure to GSH leads to the killing of surface-bound cancer cells. The dual-functionalizable hydrogel platform disclosed here can be utilized in biomedical applications where a combination of reversible and non-reversible conjugation modalities is required.
Degirmenci et al. (Thu,) studied this question.