  Biomimetic hydrogels based on natural polymers are a promising class of
biomaterial, mimicking the natural extra-cellular matrix of biological tissues
and providing cues for cell attachment, proliferation and differentiation. With
a view to providing an upstream method to guide subsequent experimental design,
the aim of this study was to introduce a mathematical model that described the
rheological properties of a hydrogel system based on covalently crosslinked
collagen triple helices. In light of their organization, such gels exhibit
limited collagen bundling that cannot be described by existing fibril network
models. The model presented here treats collagen triple helices as discrete
semi-flexible polymers, permits full access to metrics for network
microstructure, and should provide a comprehensive understanding of the
parameter space associated with the development of such multi-functional
materials. Triple helical hydrogel networks were experimentally obtained via
reaction of type I collagen with both aromatic and aliphatic diacids. The
complex modulus G* was found from rheological testing in linear shear and
quantitatively compared to model predictions. In silico data from the
computational model successfully described the experimental trends in hydrogel
storage modulus with either (i) the concentration of collagen triple helices
during crosslinking reaction or (ii) the type of crosslinking segment
introduced in resulting hydrogel networks. This approach may pave the way to a
step change in the rational design of biomimetic triple helical collagen
systems with controlled multi-functionality.
