Mechanochemical Patternable ECM-Mimetic Hydrogels for Programmed Cell Orientation

abstract

Native human tissues are supported by a viscoelastic extracellular matrix (ECM) that can adapt its intricate network to dynamic mechanical stimuli. To recapitulate the unique ECM biofunctionality, hydrogel design is shifting from typical covalent crosslinks toward covalently adaptable networks. To pursue such properties, herein hybrid polysaccharide-polypeptide networks are designed based on dynamic covalent assembly inspired by natural ECM crosslinking processes. This is achieved through the synthesis of an amine-reactive oxidized-laminarin biopolymer that can readily crosslink with gelatin (oxLAM-Gelatin) and simultaneously allow cell encapsulation. Interestingly, the rational design of oxLAM-Gelatin hydrogels with varying aldehyde-to-amine ratios enables a refined control over crosslinking kinetics, viscoelastic properties, and degradability profile. The mechanochemical features of these hydrogels post-crosslinking offer an alternative route for imprinting any intended nano- or microtopography in ECM-mimetic matrices bearing inherent cell-adhesive motifs. Different patterns are easily paved in oxLAM-Gelatin under physiological conditions and complex topographical configurations are retained along time. Human adipose-derived mesenchymal stem cells contacting mechanically sculpted oxLAM-Gelatin hydrogels sense the underlying surface nanotopography and align parallel to the anisotropic nanoridge/nanogroove intercalating array. These findings demonstrate that covalently adaptable features in ECM-mimetic networks can be leveraged to combine surface topography and cell-adhesive motifs as they appear in natural matrices.

keywords

PERIODATE-OXIDATION; STRESS-RELAXATION; GELATIN HYDROGELS; LYSYL OXIDASE; STEM-CELLS; DIFFERENTIATION; MATRIX; POLYSACCHARIDES; ADHESION; CULTURE

subject category

Engineering; Science & Technology - Other Topics; Materials Science

authors

Lavrador, P; Gaspar, VM; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

Bioengineered autonomous cell-biomaterials devices for generating humanised micro- tissues for regenerative medicine (ATLAS)

Desenvolvimento de hidrogeis de inspiracao marinha multifuncionais e de elevado desempenho para regeneracao de cartilagem, reticulados com ligacoes nao-covalentes e bio-instrutivas deslizantes. (MARGEL)

Produção de Plataformas Microcapsulares 3D+ para Avaliação Laboratorial em Larga Escala de Novas Terapias Combinatórias para o Cancro do Pâncreas (PANGEIA)

acknowledgements

The authors would like to acknowledge the support of the European Research Council for project ATLAS, grant agreement ERC-H20202014-ADG-669858. This work was also supported by the Programa Operacional Competitividade e InternacionalizacAo (POCI), in the component FEDER, and by national funds (OE) through FundacAo para a Ciencia e a Tecnologia(FCT)/MCTES, in the scope of the projects Margel (PTDC/ BTM-MAT/31498/2017) and PANGEIA (PTDC/BTM-SAL/30503/2017). The PANGEIA project is also acknowledged for the junior researcher contract of Vitor Gaspar. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTES. P.L. acknowledges an individual Ph.D. fellowship from the Portuguese Foundation for Science and Technology (SFRH/BD/141834/2018).