Supramolecular assembly of multi-purpose tissue engineering platforms from human extracellular matrix

resumo

Recapitulating the biophysical and biochemical complexity of the extracellular matrix (ECM) remains a major challenge in tissue engineering. Hydrogels derived from decellularized ECM provide a unique opportunity to replicate the architecture and bioactivity of native ECM, however, they exhibit limited long-term stability and mechanical integrity. In turn, materials assembled through supramolecular interactions have achieved considerable success in replicating the dynamic biophysical properties of the ECM. Here, we merge both methodologies by promoting the supramolecular assembly of decellularized human amniotic membrane (hAM), mediated by host-guest interactions between hAM proteins and acryloyl-beta-cyclodextrin (Ac beta CD). Photopolymerization of the cyclodextrins results in the formation of soft hydrogels that exhibit tunable stress relaxation and strain-stiffening. Disaggregation of bulk hydrogels yields an injectable granular material that self-reconstitutes into shapeadaptable bulk hydrogels, supporting cell delivery and promoting neovascularization. Additionally, cells encapsulated within bulk hydrogels sense and respond to the biophysical properties of the surrounding matrix, as early cell spreading is favored in hydrogels that exhibit greater susceptibility to applied stress, evidencing proper cell-matrix interplay. Thus, this system is shown to be a promising substitute for native ECM in tissue repair and modelling.

palavras-chave

AMNIOTIC MEMBRANE; HYDROGELS; CELLS; SPECTROSCOPY; BIOMATERIAL; XENOTRANSPLANTATION; MECHANICS; PROTEIN; MODELS; FORCES

categoria

Engineering; Materials Science

autores

Ladeira, B; Gomes, M; Wei, KC; Custódio, C; Mono, J

nossos autores

agradecimentos

The authors are grateful to Ines A. Deus for providing the decellularized amniotic membrane. The authors would also like to acknowledge the In vivo CAM assays scientific platform at i3s, Porto, for their assistance in performing the CAM assays. This work was financed by European Research Council grant agreement ERC-2019-ADG-883370 for project REBORN, by the European Union's Horizon Europe research and innovation programme under the grant agreement No. 101079482 ("SUPRALIFE") and by the Fundacao da Ciencia e Tecnologia (FCT) through the individual contract 2020.01647.CEECIND, the doctoral grant 2022.10626.BD and in the scope of project "TETRISSUE" (PTDC/BTM-MAT/3201/2020) . This work was developed at CICECO-Aveiro Institute of Materials, within the scope of project UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020) , UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) , financed by national funds through the FCT/MCTES (PIDDAC) .

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