Modulation of functional pendant chains within poly(ethylene glycol) hydrogels for refined control of protein release

Hydrogels are highly attractive delivery vehicles for therapeutic proteins. Their innate biocompatibility, hydrophilicity and aqueous permeability allow stable encapsulation and release of proteins. The release rates also can be controlled simply by altering the crosslinking density of the polymeric network. However, the crosslinking density also influences the mechanical properties of hydrogels, generally opposite to the permeability. In addition, the release of larger proteins may be hindered below critically diminished porosity determined by the crosslinking density. Herein, the physical properties of the hydrogels are tuned by presenting functional pendant chains, independent of crosslinking density. Heterobifunctional poly(ethylene glycol) monomethacrylate (PEGMA) with various end functional groups is synthesized and copolymerized with PEG dimethacrylate (PEGDA) to engineer PEG hydrogels with pendant PEG chains. The pendant chains of the PEG hydrogels consisting of sulfonate, trimethylammonium chloride, and phenyl groups are utilized to provide negative charge, positive charge and hydrophobicity, respectively, to the hydrogels. The release rates of proteins with different isoelectric points are controlled in a wide range by the type and the density of functional pendant chains via electrostatic and hydrophobic interactions

Biomaterials in Mechano-oncology: Means to Tune Materials to Study

ECM stiffness is emerging as a prognostic marker of tumor aggression or potential for relapse. However, conflicting reports muddle the question of whether increasing or decreasing stiffness is associated with aggressive disease. This chapter discusses this controversy in more detail, but the fact that tumor stiffening plays a key role in cancer progression and in regulating cancer cell behaviors is clear. The impact of having in vitro biomaterial systems that could capture this stiffening during tumor evolution is very high. These cell culture platforms could help reveal the mechanistic underpinnings of this evolution, find new therapeutic targets to inhibit the cross talk between tumor development and ECM stiffening, and serve as better, more physiologically relevant platforms for drug screening.https://scholarlycommons.pacific.edu/soecs-facbooks/1008/thumbnail.jp