H

Variable HSPG Density

FIGURE 5 Variations of ECM-GF interactions that lead to altered transport. The movement of heparin-binding GFs through ECM can be manipulated by (A) the loss of heparin binding, (B) the presence of soluble heparin, HS, or HSPG fragments, (C) variations in the heparin-binding affinity, and (D) variations in the density of HSPGs within the ECM. Abbreviations: HSPG, heparan sulfate proteoglycan; GF, growth factor; HS, heparan sulfate; ECM, extracellular matrix.

factor bound to HSPGfs can be kept in the vicinity of an injured site for a much longer time than free growth factor, providing a large reservoir of growth factor to aid in the repair of tissue. These model predictions have begun to suggest interesting possibilities regarding approaches for administering growth factors in vivo. While it is clear that these models remain an oversimplification of the complex process of growth factor interactions with and movement through ECM, they have begun to provide critical insight that might help drive the development of more optimal growth factor therapies.

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