PEG hydrogels for the controlled release of biomolecules in regenerative medicine

Abstract

Polyethylene glycol (PEG) hydrogels are widely used in a variety of biomedical applications, including matrices for controlled release of biomolecules and scaffolds for regenerative medicine. The design, fabrication, and characterization of PEG hydrogels rely on the understanding of fundamental gelation kinetics as well as the purpose of the application. This review article will focus on different polymerization mechanisms of PEG-based hydrogels and the importance of these biocompatible hydrogels in regenerative medicine applications. Furthermore, the design criteria that are important in maintaining the availability and stability of the biomolecules as well as the mechanisms for loading of biomolecules within PEG hydrogels will also be discussed. Finally, we overview and provide a perspective on some of the emerging novel design and applications of PEG hydrogel systems, including the spatiotemporal-controlled delivery of biomolecules, hybrid hydrogels, and PEG hydrogels designed for controlled stem cell differentiation.

Figure 1

(A) Simplified crosslinked hydrogel structure. Black dots represent crosslinking point; ξ represents mesh size of the gel. (B) Hydrogel property as a function of gel crosslinking density.

Figure 2

Schematic structures of PEG hydrogels formed via: (A) chain-growth, (B) step-growth, and (C) mixed-mode step and chain growth polymerization. (Components not scale to actual size)

Figure 3

Chemical structures of PEG macromer and its di(meth)acrylate derivatives that often solution polymerize to form hydrogel networks useful for cell encapsulation and other biomaterial applications.

Figure 4

Schematic of methods for loading of therapeutics into PEG hydrogels: (A) Entrapment: Drugs are loaded into hydrogels via in situ entrapment or post-fabrication equilibrium partitioning. (B) Tethering: Drugs are modified with a crosslinkable and cleavable linker that can be liberated once the tethers are degraded hydrolytically or enzymatically. (C) Multiphase loading: Drugs are pre-loaded into microparticles that are subsequently entrapped in hydrogels. (Components not scale to actual size)