Fabrication of interpenetrating polymer network to enhance the biological activity of synthetic hydrogels

A three dimensional porous hydrogel with suitable biological and mechanical properties are required for bone tissue engineering. Hydrogels of poly(lactic-ethylene oxide fumarate) (PLEOF), crosslinked with poly(ethylene glycol)-diacrylate (PEG-da) have desirable mechanical properties, however, their application for bone regeneration is limited due to the lack of cell motif sites within their structure. The aim of this study was to incorporate a naturally derived polymer such as gelatin into PLEOF hydrogels to promote their biological properties. Interpenetrating polymer network (IPN) was used as an efficient technique to acquire uniform mixture of these two polymers. Additionally gas foaming agents were used to create pores with average diameter of 250 gm in these IPN hydrogels. The concentrations of PEG-da and gelatin were optimized to tune the mechanical strength and degradation properties of these hydrogels. A compression modulus of 500 kPa was achieved for hydrogel fabricated with 400 mg/ml PLEOF, 200 mg/ml PEG-da and 150 mg/ml gelatin. The addition of gelatin to PLEOF elevated the compression modulus by two-fold and decreased the energy loss by 40%. The result of protein analysis demonstrated that IPN substantially enhanced the retention of physically crosslinked gelatin in the 3D structure of hydrogel. More than 50% of gelatin was retained in IPN hydrogel after two weeks of incubation in simulated physiological environment. Preserving gelatin in the hydrogel structure provides cell motif sites for a longer period of time, which is desirable for uniform cell proliferation. In vitro studies showed that primary human osteoblast cells adhered and proliferated in PLEOF-gelatin hydrogel. These results demonstrated the potential of using this IPN hydrogel for bone tissue engineering. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.