ABSTRACT

Extracellular Matrix ......................................................................... 133 5.1.4 Designing Control over Growth Factors to Regulate

Stem Cell Fate ................................................................................... 133 5.1.5 Chapter Scope and Key De—nitions .................................................. 133

5.2 Encapsulation of Growth Factors ................................................................. 134 5.2.1 Porous Scaffolds ............................................................................... 135 5.2.2 Hydrogel Matrices ............................................................................ 137 5.2.3 Microspheres/Microparticles ............................................................ 139 5.2.4 Embedded Microspheres .................................................................. 140 5.2.5 Dual Growth Factor Release via Co-Encapsulation ......................... 142 5.2.6 Dual Growth Factor Release via Dual Component Materials .......... 142 5.2.7 Summary .......................................................................................... 144

5.3 Covalent Immobilization of Growth Factors ................................................ 144 5.3.1 Immobilization Strategies ................................................................. 144 5.3.2 Growth Factor Immobilization to 2D Surfaces ................................ 145 5.3.3 Growth Factor Immobilization within 3D Polymer Scaffolds ......... 146 5.3.4 Immobilized Growth Factors with Degradable Linkers .................. 147 5.3.5 Summary .......................................................................................... 147

5.4 Growth Factor-Material Af—nity Interactions and Growth Factor Sequestration................................................................................................. 148 5.4.1 Material Intrinsic Interactions and Engineered Binding Domains .... 149 5.4.2 Metal-Ion Chelation .......................................................................... 149 5.4.3 Charge Interactions ........................................................................... 150 5.4.4 Heparin Functionalization and Heparin-Mimetic Peptides .............. 151 5.4.5 Heparin-Binding Peptides................................................................. 152

Tissue engineering approaches that use stem cells to modify, regenerate, or replace diseased tissue will likely require precise control over stem cell fate to create functional tissues. Included in this precise control is a need for mechanisms that locally regulate stem cell activity to generate complex tissue architectures. While many of the mature cell types needed to repair a tissue can in principle be generated by implanting a population of stem cells, the potential for uncontrolled differentiation and tumorigenesis may ultimately hinder this type of approach. For example, in a recent attempt to treat a patient with the neurodegenerative disorder ataxia telangiectasia, repeated local injections of human fetal neural stem cells (NSCs) resulted in tumor formation 4 years later.1 Although approaches using adult-derived stem cells may decrease the likelihood of such negative outcomes, the ultimate performance of a tissue engineering approach that utilizes stem cells will likely depend on the ef—- ciency with which a stem cell population can be locally differentiated into a speci—c type of mature cell. Therefore, a major focus of many tissue engineering approaches has been to incorporate biological signals that locally regulate stem cell activity.