2 research outputs found
Supramolecular Platform Stabilizing Growth Factors
High
concentrations of supplemented growth factors can cause oversaturation
and adverse effects in <i>in vitro</i> and <i>in vivo</i> studies, though these supraphysiological concentrations are often
required due to the low stability of growth factors. Here we demonstrate
the stabilization of TGF-β1 and BMP4 using supramolecular polymers.
Inspired by heparan sulfate, sulfonated peptides were presented on
a supramolecular polymer to allow for noncovalent binding to growth
factors in solution. After mixing with excipient molecules, both TGF-β1
and BMP4 were shown to have a prolonged half-life compared to the
growth factors free in solution. Moreover, high cellular response
was measured by a luciferase assay, indicating that TGF-β1 remained
highly active upon binding to the supramolecular assembly. The results
demonstrate that significant lower concentrations of growth factors
can be used when supramolecular polymers bearing growth factor binding
moieties are implemented. This approach can also be exploited in hydrogel
systems to control growth factor release
Importance of Molecular and Bulk Dynamics in Supramolecular Hydrogels in Dictating Cellular Spreading
Cellular spreading is affected not only by the stiffness
of the
matrix but also by its dynamics. Synthetic hydrogels, formed by the
assembly of supramolecular monomers, are intrinsically dynamic and
tunable in their stiffness. However, the importance of molecular dynamics
resulting in differences in bulk dynamics and stiffness remains elusive.
Here, we present two different hydrogel systems employing slow-exchanging
ureidopyrimidinone monomers and fast-exchanging benzene-1,3,5-tricarboxamide
monomers to decipher design rules for supramolecular hydrogel–cell
interactions. To achieve cell spreading, both robust incorporation
of cell-binding ligands, reflected in slow molecular dynamics (monomer
exchange), and sufficient material resistance, reflected in slow bulk
dynamics (stress relaxation), are crucial. Epithelial cells respond
to gel dynamics as cells remain round on fast-relaxing gels, independent
of gel stiffness. Fibroblasts respond to gel dynamics on soft gels
(∼100–200 Pa), but gel stiffness overrules gel dynamics
on stiffer gels (∼1 kPa). Together, our results disclose that
(1) molecular dynamics at the supramolecular fiber level is translated
to bulk dynamics on the hydrogel level, (2) gel dynamics is the dominant
factor in dictating cellular spreading in soft gels, and (3) design
rules for supramolecular hydrogel–cell interaction are cell-type-dependent