Poloxamer-based thermosensitive injectable hydrogels containing a self-assembling peptide for In situ gelation

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Drug Delivery Systems

Background:

• Poloxamer 407 (P407) hydrogels are widely used but often lack sufficient mechanical strength for therapeutic applications.
• Enhancing the properties of injectable hydrogels is crucial for effective site-specific drug delivery and tissue regeneration.

Purpose of the Study:

• To develop and characterize a novel thermosensitive injectable hydrogel by incorporating a self-assembling peptide into P407.
• To improve the biomechanical properties, gelation kinetics, and therapeutic cargo release of P407 for intra-articular (i.a.) applications.

Main Methods:

• Formulation of a P407-peptide hybrid hydrogel.
• Assessment of gelation time and rheological properties (storage modulus).
• In vitro biocompatibility testing using human chondrocytes (MTS assay, LIVE/DEAD staining).
• In vivo evaluation in an osteoarthritis mouse model using near-infrared fluorescent (NIRF) dye tracking.

Main Results:

• The P407-peptide hydrogel exhibited significantly faster gelation compared to P407 alone.
• Rheological analysis showed a 1.5 kPa increase in storage modulus, indicating enhanced mechanical integrity.
• In vitro studies confirmed no cytotoxicity to human chondrocytes.
• In vivo tracking demonstrated successful localized gelation and sustained delivery in an OA mouse model.

Conclusions:

• The novel P407-peptide hydrogel presents a promising platform for intra-articular therapeutic delivery.
• The formulation combines injectability, rapid thermoresponsive gelation, improved mechanical reinforcement, and controlled release capabilities.
• This enhanced hydrogel is well-suited for regenerative medicine strategies and the treatment of osteoarthritis.