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Abstract
Successful tissue regeneration requires that biomaterials have optimal bioactivity
and mechanical properties. Heparin-containing hydrogels that can be crosslinked in
situ were designed to contain tunable amounts of biological components (e.g. heparin,
arginine-glycine-aspartate (RGD)) as well as to exhibit controlled mechanical properties
(e.g. shear modulus). These gel parameters can also be tuned to provide controlled
delivery of proteins, such as growth factors, for regulating cellular behavior. Maleimide-functionalized
low-molecular-weight heparin (LWMH) was conjugated to a poly(ethylene glycol) (PEG)
hydrogel. The elastic shear modulus, as assessed via oscillatory rheology experiments,
could be tuned by the concentration of polymer in the hydrogel, and by the end group
functionality of PEG. Hydrogels of two different moduli (2.8 and 0.4kPa) were used
to study differences in the response of human aortic adventitial fibroblasts (AoAF)
in two-dimensional cell culture experiments. These experiments indicated that the
AoAFs show improved adhesion to materials with the higher modulus. Evaluation of cell
responses to hydrogels with RGD linked to the hydrogels via conjugation to PEG or
to LMWH indicated improved cellular responses to these materials when the bioactive
ligands were chemically attached through linkage to the PEG rather than to the LMWH.
These results highlight important design considerations in the tailoring of these
materials for cardiovascular tissue engineering applications.