Characterization of protein release from poly(ethylene glycol) hydrogels with crosslink density gradients

Abstract

Transplantation of cells within poly(ethylene glycol) (PEG) hydrogel scaffolds as effective immunoisolation barriers is becoming increasingly important strategy for tissue engineering and regenerative medicine. In these applications, crosslink density of these membranes has significant effect on the control of diffusion of many biomolecules such as nutrients, cellular wastes, and hormones. When these networks are designed with crosslink density gradients, alterations in network structure may have an effect on biomolecule diffusivity. The goal of this work was to synthesize PEG hydrogels via surface initiated photopolymerization for use in applications involving physiological protein delivery and cell encapsulation. For this purpose, PEG hydrogels of differing crosslink density gradients were formed via surface initiated photopolymerization, and the diffusion of model proteins with various molecular weights were observed through these PEG hydrogel scaffolds with defined properties. Diffusion coefficients were on the order of 10(-7) -10(-8) cm(2) /s and protein diffusion time scales varied from 5 min to 30 h. The results confirm that synthetic PEG hydrogels with crosslink density gradients are promising for controlled release of bioactive molecules and for covalent incorporation of ligands to support cell viability.

Controlling the Release of Small, Bioactive Proteins via Dual Mechanisms with Therapeutic Potential

“…Indeed, Kizilel and coworkers reported rapid release of bovine serum albumin (BSA, hydrodynamic radius = 3.56 nm) and glucagon-like peptide (GLP-1, hydrodynamic radius = 1.3 nm) from similar PEG hydrogels. [30] Approximately ~80% of the loaded BSA was released within 3000 min, whereas GLP-1 was released within 300 min, highlighting the importance of heparin-mediated electrostatic interactions for the sustained release of small proteins from PEG-based hydrogels.…”

Diffusion and interaction in PEG-DA hydrogels

“…As they exhibit many advantageous material properties such as being transparent, deformable, biocompatible [14], and permeable to gases and nutrients [15], PEG hydrogels are widely used in biomedical applications including artificial tissue scaffolds, matrices for the controlled release of biomolecules [14], wound dressings [16], and contact lenses [17]. Thus, understanding diffusion mechanisms within PEG hydrogels and understanding them with respect to the polymeric structure is of great interest.…”

Long‐Term Controlled Protein Release from Poly(Ethylene Glycol) Hydrogels by Modulating Mesh Size and Degradation

“…Hydrogel degradation triggered by hydrolysis or enzymes have been previously employed to promote protein release [7b, 14a, 20] . However, the initial mesh size of hydrogels are often larger than loaded proteins, which led to burst release even without degradation [7b] .…”

“…To achieve efficient protein loading and prolonged release, the mesh size of the network should be smaller than the hydrodynamic radius of the protein(s) of interest, but most current hydrogels have mesh sizes that are too large [7b, 14] . Since PEG is bioinert and repulses proteins, entrapped proteins are likely to be released in bursts, with >80% of the cargo released within a few hours of encapsulation [7b, 14] . Protein release is also sensitive to heterogeneity in the hydrogel network, which occurs when monomers crosslink in a random sequence.…”

“…In contrast, step-growth polymerization involves crosslinking between end groups of multi-arm PEG molecules. Since the crosslinks are pre-defined as the cores of the multi-arm molecules, the hydrogel networks constructed through this method exhibit more defined structures, increased homogeneity, and increased control over mesh size [14a, 17] .…”