| Discoveries in biology have encouraged the development of stimuli-responsive materials. When coupled with principles of developmental biology, biologically sensitive materials offer not only a method for interacting with living tissue both in vitro and in vivo, but also the possibility of repairing diseased or damaged tissue. In addition, materials that mimic biological associations and self assembly mechanisms show exceptional promise as new vehicles for the emerging fields of tissue engineering and drug delivery. In an attempt to create a new class of biomimetic materials, a unique hydrogel system has been developed, which mimics the extracellular matrix with respect to both composition and assembly. This system depends on the physical crosslinks created between heparin and heparin binding peptides covalently coupled to multiarm poly(ethylene glycol). An analysis of the viscoelastic response of a purely physical gel-like matrix revealed that physical gelation occurred immediately upon mixing of the gel components. In addition, dynamic mechanical properties were dependent on frequency and temperature. Although the mechanical response of physical matrices resembled those of high molecular weight polymer melts, the magnitudes of the elastic moduli remained comparable to those obtained for covalent gels. Further characterization of additional gel compositions showed that the presence of enzymatically sensitive crosslinks could stabilize the matrix without eliminating the temperature and frequency dependence of the viscoelastic response. In addition to exhibiting impressive mechanical properties, the crosslink stabilized material system was shown to be biocompatible and sensitive to enzymatic degradation. Investigations related to the potential of these materials to serve as drug delivery vehicles revealed that the materials could be loaded with millimolar concentrations of heparin binding therapeutic analogues without compromising mechanical integrity and could release these analogues at significantly different rates based on relative heparin affinity. Overall, this system represents a unique approach to biomaterials design relative to other existing examples of stimuli-responsive gels. In addition, this system may have broader implications to the field of biomedical research by serving as a model for studying the dynamics between physical and covalent interactions within tissues and by providing new scaffolds for drug delivery, wound healing, and regenerative medicine. |