Synthetic PEG Hydrogels as Extracellular Matrix Mimics for Tissue Engineering Applications

In recent years the field of tissue engineering, or regenerative medicine, has developed from the need to replace damaged and/or diseased tissues and organs by combining biomaterial scaffolds, biological signaling molecules, and cells. The regeneration of tissues may be achieved using either one of two principle approaches: 1) the in vitro construction or 2) the in vivo induction of tissue. In the first approach, biomaterial scaffolds are combined with biofunctional signaling molecules and cells and a fully functional tissue is grown in vitro which can then be implanted into the host. In the second approach, scaffolds are tailored with the desired biochemical composition as well as physical and mechanical properties of the target tissue, implanted into the host, and the body is used as a bioreactor to regenerate the tissue of interest. Therefore, biomaterial scaffolds play a central role in regenerative medicine as physical and biochemical milieus that dictate cell behavior, function, and tissue regeneration (Lutolf & Hubbell, 2005). While both natural and synthetic biomaterials have been extensively explored as scaffolds for tissue regeneration, polymeric materials from synthetic sources are advantageous due to their tunable mechanical properties and ability to systematically and selectively incorporate biological signals of the natural extracellular matrix (ECM) enabling controlled study of cell-substrate interactions. Over the last several decades synthetic crosslinked hydrogels of poly(ethylene) glycol have been extensively investigated for numerous biomedical applications including drug delivery, immunoisolation, and as matrices for engineering tissues. PEG hydrogels are biocompatible, hydrophilic polymers composed of 3D interstitial crosslinks that swell extensively in aqueous environments with water content similar to soft tissues. These biomaterials are inherently resistant to non-specific cell adhesion and protein adsorption, thus providing a blank slate upon which ECM-derived signals can be systematically introduced as well as spatially and temporally manipulated to control cell behavior and tissue regeneration. The continued enhancement of PEG-based biomaterial strategies towards the rational design of scaffolds is highly dependent on their ability to independently control the incorporation of multiple biofunctional signaling molecules from alterations in hydrogel degradation kinetics and mechanical properties, to temporally and spatially tune the presentation of mechanical and biofunctional signals, and to promote rapid and guided neovascularization (new blood vessel formation) prior to complete material degradation. The combination of the above-