Injectable thermosensitive gels for the localized and controlled delivery of biomolecules in tissue engineering/regenerative medicine

Abstract

The characteristic poor stability and high fluid permeability of Poloxamer®- based gels have severely limited their biomedical application. In this work, Poloxamer 407 was used as building block to synthesize a poly(ether urethane) (PEU), which aqueous solutions formed gels with improved stability and mechanics compared to Poloxamer itself. PEU chains formed micelles in aqueous solution (diameter ~40 nm at 25°C) and systems with PEU content higher than 5±1% w/v underwent a temperature- driven gelation. Gel properties were tuned acting on PEU concentration in the starting solutions, with compositions within the range 8-18% w/v showing high potential for biomedical applications (gelation at 37°C within 3-10 minutes, residence time from few days to many weeks, injectability). Model proteins (bovine serum albumin, horseradish peroxidase) were encapsulated in mild conditions and their release was modulated by gel composition (on day 3, approx. 85, 65 and 55% of encapsulated payload released from gels with 8, 15 and 18% w/v concentration). Released peroxidase retained approx. 30-40% of its activity up to 2 days, a key aspect for biomolecules in the drug delivery field.