A Versatile Biosynthetic Hydrogel Platform for Engineering of Tissue Analogues

Abstract

For creating functional tissue analogues in tissue engineering, stem cells require very specific 3D microenvironments to thrive and mature. Demanding (stem) cell types that are used nowadays can find such an environment in a heterogeneous protein mixture with the trade name Matrigel. Several variations of synthetic hydrogel platforms composed of poly(ethylene glycol) (PEG), which are spiked with peptides, have been recently developed and shown equivalence to Matrigel for stem cell differentiation. Here a clinically relevant hydrogel platform, based on PEG and gelatin, which even outperforms Matrigel when targeting 3D prevascularized bone and liver organoid tissue engineering models is presented. The hybrid hydrogel with natural and synthetic components stimulates efficient cell differentiation, superior to Matrigel models. Furthermore, the strength of this hydrogel lies in the option to covalently incorporate unmodified proteins. These results demonstrate how a hybrid hydrogel platform with intermediate biological complexity, when compared to existing biological materials and synthetic PEG‐peptide approaches, can efficiently support tissue development from human primary cells.

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

“…[ 24 ] This effect could in the future be alleviated by introducing other groups, which cannot be protonated, onto the surface of the CNFs instead of the carboxyl groups. In addition, incorporation of moieties that stimulate cell activity and proliferation, as shown in other hydrogels, [ 35 ] could improve the overall functionality of the hepatocyte‐like organoids.…”

“…In all tested genes except for CYP1A2, which did not display any differences, expression levels showed successful differentiation, as they were consistently higher than levels in organoids remaining in EM. Results are comparable to other organoid studies in MG and poly(ethylene glycol) hydrogels, [ 9,35,39 ] as well as with cell lines (HepaRG progenitor cells) in nanofibrillar cellulose and hyaluronan‐gelatin (HG) hydrogels. [ 8 ]…”

Assembly of FN-silk with laminin-521 to integrate hPSCs into a three-dimensional culture for neural differentiation

“…12 Recently, a hybrid hydrogel with natural (gelatin) and synthetic (PEG) components were shown to stimulate cell differentiation (in this case mesenchymal stem cells). 13 Permeability of the matrix is crucial to allow exchange of nutrients and waste products. Furthermore, the stiffness of the material is known to be important for cellular behavior.…”

Stiff-to-Soft Transition from Glass to 3D Hydrogel Substrates in Neuronal Cell Culture

“…Previously, we similarly demonstrated SH-SY5Y in nanogroove-enhanced hydrogel scaffolds for a 3D neuronal cell culture as an easy access brain-on-a-chip model utilizing Matrigel instead [ 15 ]. Matrigel is a well-known hydrogel of a natural source implemented in many different types of tissue engineering applications requiring a 3D scaffold construct [ 26 ]. As Matrigel has rich protein components, such as collagen, heparan sulfate proteoglycan, and laminin, it is very good at mimicking the extracellular matrix (ECM).…”