Sustained growth factor delivery in tissue engineering applications

The beautifully orchestrated complexity of the temporal spatial growth factor gradients during embryogenesis offer a striking contrast to systemic bolus administration that lack tissue specificity and sustained protein localization, often requiring supraphysiological protein doses to produce the desired therapeutic dose. These attributes may be responsible for clinically observed dangerous tissue overgrowth, inflammation, and even tumor formation. Growth factor delivery within an implanted scaffold is a very attractive way to modulate cell behavior. For short term delivery, proteins can be non-specifically adsorbed to the material surface or simply entrapped within the bulk scaffold. For more sustained delivery, many researchers have turned to the ever increasing list of covalent immobilization methods that have profound applications in purification, biosensing, imaging, and drug discovery by tethering proteins, nucleic acids, carbohydrates, synthetic polymers, small molecules, nanotubes, and even whole cells. This review focuses on the use of covalent immobilization to achieve sustained growth factor delivery for tissue engineering. Covalent immobilization techniques will be reviewed in terms of design, protein bioactivity/stability, efficiency, and spatiotemporal distribution. Further, the biological response to sustained growth factor delivery will also be covered, such as cell interaction, cell responsiveness, proliferation, differentiation, extracellular matrix production, and tissue regeneration. This focused review is anticipated to inform investigators on the selection of optimal immobilization strategies for their specific applications.