A Chemically Defined Hydrogel for Human Liver Organoid Culture

End-stage liver diseases are an increasing health burden, and liver transplantations are currently the only curative treatment option. Due to a lack of donor livers, alternative treatments are urgently needed. Human liver organoids are very promising for regenerative medicine; however, organoids are currently cultured in Matrigel, which is extracted from the extracellular matrix of the Engelbreth-Holm-Swarm mouse sarcoma. Matrigel is poorly defined, suffers from high batch-to-batch variability and is of xenogeneic origin, which limits the clinical application of organoids. Here, a novel hydrogel based on polyisocyanopeptides (PIC) and laminin-111 is described for human liver organoid cultures. PIC is a synthetic polymer that can form a hydrogel with thermosensitive properties, making it easy to handle and very attractive for clinical applications. Organoids in an optimized PIC hydrogel proliferate at rates comparable to those observed with Matrigel; proliferation rates are stiffness-dependent, with lower stiffnesses being optimal for organoid proliferation. Moreover, organoids can be efficiently differentiated toward a hepatocyte-like phenotype with key liver functions. This proliferation and differentiation potential maintain over at least 14 passages. The results indicate that PIC is very promising for human liver organoid culture and has the potential to be used in a variety of clinical applications including cell therapy and tissue engineering

Effects of surfactant and urea on dynamics and viscoelastic properties of hydrophobically assembled supramolecular hydrogel

Physically associated hydrogels based on strong hydrophobic interactions often have attractive mechanical properties that combine processability with elasticity. However, there is a need to study such interactions and understand their relation to the macroscopic hydrogel properties. Therefore, we use the surfactant sodium dodecyl sulfate (SDS) and urea as reagents that disrupt hydrophobic interactions. The model hydrogel is based on a segmented copolymer between poly(ethylene glycol) (PEG) and hydrophobic dimer fatty acid (DFA). We show that both agents influence viscoelastic properties, dynamics, and relaxation processes of the model hydrogel. In particular, the relaxation time is significantly reduced by urea, as compared to SDS, whereas the surfactant causes a decrease of the modulus of the hydrogel more efficiently. The reversibility of the effects of SDS and urea can be exploited, for instance, by using an injectable sol that solidifies when the SDS or urea diffuses out of the sample. Surfactant-induced processability may be advantageous in future applications of hydrophobically assembled physical hydrogels

Effects of Surfactant and Urea on Dynamics and Viscoelastic Properties of Hydrophobically Assembled Supramolecular Hydrogel

Physically associated hydrogels based on strong hydrophobic interactions often have attractive mechanical properties that combine processability with elasticity. However, there is a need to study such interactions and understand their relation to the macroscopic hydrogel properties. Therefore, we use the surfactant sodium dodecyl sulfate (SDS) and urea as reagents that disrupt hydrophobic interactions. The model hydrogel is based on a segmented copolymer between poly­(ethylene glycol) (PEG) and hydrophobic dimer fatty acid (DFA). We show that both agents influence viscoelastic properties, dynamics, and relaxation processes of the model hydrogel. In particular, the relaxation time is significantly reduced by urea, as compared to SDS, whereas the surfactant causes a decrease of the modulus of the hydrogel more efficiently. The reversibility of the effects of SDS and urea can be exploited, for instance, by using an injectable sol that solidifies when the SDS or urea diffuses out of the sample. Surfactant-induced processability may be advantageous in future applications of hydrophobically assembled physical hydrogels

Tough Supramolecular Hydrogel Based on Strong Hydrophobic Interactions in a Multiblock Segmented Copolymer

We report the preparation and structural and mechanical characterization of a tough supramolecular hydrogel, based exclusively on hydrophobic association. The system consists of a multiblock, segmented copolymer of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dimer fatty acid (DFA) building blocks. A series of copolymers containing 2K, 4K, and 8K PEG were prepared. Upon swelling in water, a network is formed by self-assembly of hydrophobic DFA units in micellar domains, which act as stable physical cross-link points. The resulting hydrogels are noneroding and contain 75–92 wt % of water at swelling equilibrium. Small-angle neutron scattering (SANS) measurements showed that the aggregation number of micelles ranges from 2 × 102 to 6 × 102 DFA units, increasing with PEG molecular weight. Mechanical characterization indicated that the hydrogel containing PEG 2000 is mechanically very stable and tough, possessing a tensile toughness of 4.12 MJ/m3. The high toughness, processability, and ease of preparation make these hydrogels very attractive for applications where mechanical stability and load bearing features of soft materials are required