ABSTRACT
I. The Extracellular Matrix — A Prototypical Bioactive Hydrogel ................................. 275
II. Modification of Hydrogel Materials with Cell Adhesion Ligands ............................... 275
III. Growth Factor Immobilization ...................................................................................... 277
IV. Proteolytically Degradable Hydrogels ........................................................................... 278
V. Conclusions .................................................................................................................... 280
References ................................................................................................................................... 280
In all soft tissues in our bodies, cells grow within or on a hydrogel scaffold consisting of a variety of
cross-linked proteins and polysaccharides called the extracellular matrix (ECM). The ECM
provides mechanical support for cells within the tissue and also has direct biological interactions
with the tissue cells, influencing cell adhesion, growth, migration, gene expression, morphology,
and differentiation. Ideally in applications such as tissue engineering, we would like to replace
many of the functions of the ECM in order to control and optimize the tissue formation process, but
biomaterials used as scaffolds in tissue engineering generally serve solely as mechanical support
structures. Using natural polymers such as collagen or fibrin gels provides many of the biological
activities and cues, but controlling these interactions is difficult, and frequently the mechanical
properties of these protein-based materials are insufficient. One option may be to create biohybrid
materials composed primarily of synthetic polymers but modified with bioactive moieties such as
peptides, proteins or polysaccharides. This may allow one to provide the requisite mechanical
support as well as provide signals to control tissue formation and differentiation. Some of the
modifications that could mimic, at least to some extent, the biological functions of the ECM would
include incorporation of cell adhesive ligands, immobilization of agents with growth factor activity,
and inclusion of proteolytically degradable domains within the polymer structure to allow hydrogel
degradation in response to cellular remodeling activity.
