Issue 14, 2023

Fabrication of hydrogel microspheres via microfluidics using inverse electron demand Diels–Alder click chemistry-based tetrazine-norbornene for drug delivery and cell encapsulation applications

Abstract

Microfluidic on-chip production of polymeric hydrogel microspheres (MPs) can be designed for the loading of different biologically active cargos and living cells. Among different gelation strategies, ionically crosslinked microspheres generally show limited mechanical properties, meanwhile covalently crosslinked microspheres often require the use of crosslinking agents or initiators with limited biocompatibility. Inverse electron demand Diels Alder (iEDDA) click chemistry is a promising covalent crosslinking method with fast kinetics, high chemoselectivity, high efficiency and no cross-reactivity. Herein, in situ gellable iEDDA-crosslinked polymeric hydrogel microspheres are developed via water-in-oil emulsification (W/O) glass microfluidics. The microspheres are composed of two polyethylene glycol precursors modified with either tetrazine or norbornene as functional moieties. Using a single co-flow glass microfluidic platform, homogenous MPs of sizes 200–600 μm are developed and crosslinked within 2 minutes. The rheological properties of iEDDA crosslinked bulk hydrogels are maintained with a low swelling degree and a slow degradation behaviour under physiological conditions. Moreover, a high-protein loading capacity can be achieved, and the encapsulation of mammalian cells is possible. Overall, this work provides the possibility of developing microfluidics-produced iEDDA-crosslinked MPs as a potential drug vehicle and cell encapsulation system in the biomedical field.

Graphical abstract: Fabrication of hydrogel microspheres via microfluidics using inverse electron demand Diels–Alder click chemistry-based tetrazine-norbornene for drug delivery and cell encapsulation applications

Supplementary files

Article information

Article type
Paper
Submitted
20 Feb 2023
Accepted
12 Jun 2023
First published
13 Jun 2023
This article is Open Access
Creative Commons BY license

Biomater. Sci., 2023,11, 4972-4984

Fabrication of hydrogel microspheres via microfluidics using inverse electron demand Diels–Alder click chemistry-based tetrazine-norbornene for drug delivery and cell encapsulation applications

R. Pareja Tello, S. Wang, F. Fontana, A. Correia, G. Molinaro, S. López Cerdà, S. Hietala, J. Hirvonen, G. Barreto and H. A. Santos, Biomater. Sci., 2023, 11, 4972 DOI: 10.1039/D3BM00292F

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