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

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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2023-06-13

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en

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13

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Biomaterials Science, Volume 11, issue 14, pp. 4972-4984

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.

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Funding Information: Prof. H. A. Santos acknowledges financial support from the Academy of Finland (Grant No. 331151). S. Wang acknowledges Academy of Finland (decision no. 331106) for financial support. This project has received funding from the European Union's Horizon 2020 research and development programme under the Marie Skłodowska Curie grant agreement No. 955685. The authors thank the Light Microscopy Unit, Institute of Biotechnology, University of Helsinki (supported by HiLIFE and Biocenter Finland) for scanning electron microscope and confocal imaging. Publisher Copyright: © 2023 The Royal Society of Chemistry.

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Pareja Tello, R, Wang, S, Fontana, F, Correia, A, Molinaro, G, López Cerdà, S, Hietala, S, Hirvonen, J, Barreto, G & Santos, H A 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 ', Biomaterials Science, vol. 11, no. 14, pp. 4972-4984 . https://doi.org/10.1039/d3bm00292f