Local patterning of biophysical and biochemical properties – a smart tool for the design of biomaterials in regenerative medicine

Biomaterials with patterned biophysical and biochemical properties are of great interest in the field of regenerative medicine, as they allow spatial control and guidance of cell behaviour. Nanotechnology significantly impacted the field of tissue engineering by providing new ways to introduce complex spatial and temporal biochemical and biophysical patterns into biomaterials. Biochemical patterning contributes to patterns in degradation, delivery and/or presentation of various bioactive molecules and diversity in biochemical environment for invading/adhering cells. Biophysical patterning may introduce variations in stiffness and topographical cues. All these patterns enable local control over cell behaviour, e.g. differentiation, and tissue infiltration. Patterned tissue infiltration is an important step towards guiding endogenous healing responses.

Scientists from Charité, Max Planck Institute of Colloids and Interfaces, and Harvard University recently published a paper on “Dual alginate crosslinking for local patterning of biophysical and biochemical properties.” The presented biomaterial system features norbornene- and tetrazine-modified alginate and a dithiol crosslinker or monothiol peptide and can be used to fabricated hydrogels with different kinds of patterns, stiffness, biomolecule presentation and degradation. These biophysical and biochemical properties are expected to stimulate different cell behaviours on a local level to guide endogenous regeneration processes in vivo. Patterning is achieved by controlling the spatial location of the light-induced reaction (thiol-en) using photomasks. The materials were characterized for their topographical features, their mechanical properties and then subjected to different cellular assays and in vivo testing.

Result excerpt: Fibroblasts aligned in the direction of the stripe pattern and migrated to stiff regions within few hours, resulting in approx. 6 times higher numbers of cells attached to stiff stripes than soft stripes. In the case of mesenchymal stem cell differentiation, more oil droplets (adipocenid marker) formed on soft substrates, while more mineralized deposits (osteogenic marker) formed on stiff substrates. Cell attachment and morphology of mouse pre-osteoblasts on RGD-patterned alginate hydrogels showed that cells predominantly attached to regions with covalently attached RGD, not due to mechanical properties, but biomolecule presentation differences.

These selected results highlight the importance of local biophysical and biochemical properties to direct diverse behaviours of different cell types. Patterned hydrogels therefore enable orchestrated local cell responses, both for fundamental studies and in tissue engineering applications to support endogenous healing processes.

Creator: Jacobs School of Engineering, UC San Diego. Source:

Original paper: A. Lueckgen et al., Acta Biomaterialia 2020: