A cell-compatible PEO–PPO–PEO (Pluronic®)-based hydrogel stabilized through secondary structures

• Modification of Pluronic-F127 with oligo(peptides) decreased gelation concentration and prolonged residence time in vitro and in vivo.
• Oligo(peptide)-modified Pluronic-F127 exhibited critical gelation concentration as low as 5%.
• Cells encapsulated within 5% oligo(peptide)-modified hydrogel proliferated within a period of 7 days.
• Oligo(peptide)-modified hydrogels were retained beneath the skin for 2 weeks while Pluronic hydrogel disintegrated within 3 days.

Pluronic F-127 (PF127) is a thermosensitive polymer that has been widely recognized as a potential candidate for various bio-applications. However, in hydrogel form, its rapid disintegration and inhospitality toward cells have significantly limited its usage. As a means to increase the integrity and cell compatibility of a PF127 hydrogel, we propose the introduction of stabilizing secondary structures to the gel network by the addition of secondary structure-forming oligo-alanine and oligo-phenylalanine. Results indicate that increasing the oligo(peptides) attached to PF127 led to a significant decrease in the gelation concentration and temperature. A selected oligo(peptide)-modified PF127 was capable of forming a stable hydrogel network at 5% and suffered only 20% weight loss after 7 days of incubation in media. Scanning electron microscopy (SEM) revealed comparably more interconnected morphology in modified hydrogels which may be attributed to the presence of secondary structures, as verified by circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy. Nuclear magnetic resonance (NMR) provided insights into the extensive interactions at the micelle core, which is the key to altered gelation behavior. Furthermore, modified hydrogels maintained structural integrity within culturing media and supported the proliferation of encapsulated chondrocytes. In addition, in vivo residence time was extended to well beyond 2 weeks after oligo(peptide) modification, thereby broadening the application scope of the PF127 hydrogel to encompass long-term drug delivery and cell culturing.