PEG-hydrogels, suitable carriers for application of proteins in bony defects?

Objectives: The use of osteoinductive or osteopromotive proteins opens up new possibilities in bone regeneration. An appropriate carrier system for the application and controlled delivery of these proteins, however, is essential. The aim of this study was to investigate, whether polyethylene glycol (PEG) based hydrogels are suitable as carrier system for bony defects.

Methods: To evaluate a possible influence of PEG on osteoblasts, passage 2 differentiated and non differentiated calvarial osteoblasts isolated from 0 day old rats were incubated with PEG for 10 days. Total RNA was isolated after 0-10 days and Real-Time RT-PCR was performed measuring alkaline phosphatase, osteopontin, osteonectin and bone sialoprotein mRNA expression.

To investigate whether PEG fulfills the demands of a sustained protein delivery, the release of a 5kD protein incorporated in cylindrical PEG-samples, floating in cell culture medium, was tracked over 72 hours. The medium was removed 3, 6, 24, 48 and 72h after incubation and dot blotting with an antibody against the 5kD protein was performed.

Clinical applicability and in vivo behaviour of PEG in bony defects was tested in cylindrical defects, prepared in the jaws of adult rats and filled with PEG or left unfilled. Two different PEG hydrogel formulations, exhibiting a rapid (MX-10) or a slower (MX-28) degradation rate, were applied as liquid, granules, inserts or in combination with a synthetic bone substitute. Tissue samples were collected at 1, 2 and 3 weeks after surgery and prepared for microscopic examination.

Results: PEG showed no negative influence on osteoblasts and exhibited a sustained protein delivery. Histological evaluation revealed a good tissue compatibility of PEG which was immediately replaced by osseous tissue after degradation. A combination with a mineral bone substitute seems to be beneficial.

Conclusion: PEG may be a suitable carrier for proteins in bony defects.