Delivery of growth factors via bijels-derived hybrid hydrogels

Abstract

Bicontinuous interfacially jammed emulsion gels (“bijels”) can be used as templates to fabricate bijels-derived structures, which maintain the bicontinuous internal structure of bijels and hence possesses unique properties for various applications. Bijels-derived structures are potential delivery vehicles for the controlled release of growth factors (GFs) in tissue engineering. To apply bijels-derived structures in tissue engineering, the biocompatibility requirement must be met but most existing bijels-derived structures are not biocompatible. Using biocompatible materials such as hydrogels may provide solutions for solving the problems. Bioactive molecules, particularly GFs, have been used in tissue regeneration. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are often used in the regeneration of tissues such as skin and gastrointestinal tract. Controlled delivery of GFs through appropriate vehicles can promote tissue regeneration. This study investigated the fabrication and characteristics of hybrid hydrogels consisting of biocompatible materials made via bijels for VEGF and PDGF delivery. A modified solvent induced phase separation process was used to fabricate bijelsderived hybrid hydrogel membranes. A ternary liquid mixture was made by adding pure ethanol, hexanedioldiacrylate (HDA), 2-hydroxy-2-methylpropiophenone (HMP), deionized water, Ludox TMA (silica nanoparticle suspension) and CTAB in ethanol A glass plate was immersed in the ternary mixture for forming a mixture film on its surface. It was taken out and then immersed in a water bath to form bijels membranes through phase transition. A high-intensity UV light was applied to cure HDA and harden the bijels structure. Then bijels films were immersed in VEGF- or PDGFcontaining Na-alginate solutions, taken out and immersed in CaCl2 solution for crosslinking, forming GF-containing bijels-derived hybrid hydrogel membranes. The bicontinuous microstructure in membranes could be clearly seen under SEM. UV-cured HDA polymer and crosslinked CA-alginate hydrogel formed two continuous phases in the membrane. The diameter of the bicontinuous structure (channel size) could be adjusted by UV-curing time and other parameters. In in vitro experiments of as-fabricated hybrid hydrogel membranes, human dermal fibroblasts (HDF) were cultured on membranes whose biocompatibility was assessed using LIVE/DEAD assay. At Day 3, fibroblasts proliferated on membranes and nearly no cell death was observed. MTT assay was used to evaluate cell proliferation on membranes. Results showed good cell proliferation after 1, 2, 3-day culture. Following the established test protocol, the in vitro release behavior of VEGF and PDGF for bijels-derived membranes was studied. Steady and sustained releases of VEGF and PDGF were both seen within test durations. This study demonstrates the high potential of bijels technology in the tissue engineering field.