Freeform 3D Printing of Cell-Adsorptive Cryogels with Shape-Recoverability

abstract

The intricate porous network of cryogels enhances diffusivity, injectability, and shape-recovery properties, providing a valuable tool for minimally invasive biomedical applications. However, the injection of cell-loaded complex structures remains highly challenging. Here, we demonstrate the freeform 3D printing of fully protein-based macroporous cryogels with cell-adsorptive and shape-recoverable features. The 3D-printed cryogels surpass conventional cryogels, revealing successful injection, cell-adsorptive features, and a high interconnected porosity (99.2%). The rapid hydration process enables the efficient incorporation of individual cells or spheroids into the cryogel network. Using an in-liquid cell aspiration method, the constructs retained cellular content up to 89%, with in vitro culture revealing high viability and cell spreading over 14 days. Our findings highlight the potential of the cryogels' macroporosity for cell loading and injectability. We anticipate that these off-the-shelf cryogels will pave the way for a new generation of self-adsorptive and injectable cryogels.

keywords

BIOMATERIALS; HYDROGELS; SCAFFOLDS; TISSUES

subject category

Materials Science

authors

Castanheira, EJ; Monteiro, LPG; Sobreiro-Almeida, R; Gaspar, VM; Wittig, NK; Correia, TR; Birkedal, H; Rodrigues, JMM; Mano, JF

our authors

acknowledgements

Work developed under the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI: 10.54499/UIDB/50011/2020), UIDP/50011/2020 (DOI: 10.54499/UIDP/50011/2020), and LA/P/0006/2020 (DOI: 10.54499/LA/P/0006/2020), financed by national funds through the FCT/MEC (PIDDAC). This work was also funded by the Programa Operacional Competitividade e Internacionalizacao (POCI) and Programa Operacional Regional do Centro - Centro 2020, in the component FEDER, through FCT/MCTES in the scope of the project COP2P (PTDC/QUIQOR/30771/2017-POCI-01-0145-FEDER-30771), and also funded by European Union's Horizon 2020 research and innovation programme under the scope of InterLynk project (grant agreement No 953169). E.J.C, L.P.G.M., R.S.A, V.M.G., and J.M.M.R. gratefully acknowledge FCT for the individual PhD grants (SFRH/BD/144880/2019 - E.J.C.; DOI: 10.54499/2020.06767.BD - L.P.G.M.) and individual researcher contracts (DOI: 10.54499/2022.04605.CEECIND/CP1720/CT0021 - R.S.A.; DOI: 10.54499/2022.02106.CEECIND/CP1720/CT0028 - V.M.G.; 2023.07239.CEECIND - J.M.M.R.), respectively. Use of the Novo Nordisk Foundation research infrastructure AXIA (grant NNF19OC0055801) is gratefully acknowledged. Lastly, the authors would like to acknowledge SMART - Servier Medical Art (https://smart.servier.com) for providing free licensed images, which were used in the creation of figures in this manuscript. Images were modified as needed to fit the context of the study.

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