An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate

• Published in: Biomaterials Vol. 32; no. 2; pp. 587 - 597
• Main Authors: Pritchard, Christopher D, O’Shea, Timothy M, Siegwart, Daniel J, Calo, Eliezer, Anderson, Daniel G, Reynolds, Francis M, Thomas, John A, Slotkin, Jonathan R, Woodard, Eric J, Langer, Robert
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-01-2011
• Subjects: Advanced Basic Science; Animals; Biomaterials; Biomedical materials; Cell adhesion; Cells, Cultured; Controlled drug release; Dentistry; Elastic modulus; Hydrogel; Hydrogels; Hydrogels - chemistry; Injections; Mesenchymal Stem Cells - metabolism; Methylprednisolone Hemisuccinate - administration & dosage; Methylprednisolone Hemisuccinate - chemistry; Mice; Peptide; Peptides; Polyethylene Glycols - chemistry; Polyethylene oxide; Sodium; Spectroscopy, Fourier Transform Infrared; Spinal surgery; Sulfhydryl Compounds - chemistry; Surgical implants; Sustained release; Toxicity; Controlled drug release; Hydrogel; Polyethylene oxide; Peptide; Spinal surgery; Cell adhesion
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.08.106

Abstract Clinically available injectable hydrogels face technical challenges associated with swelling after injection and toxicity from unreacted constituents that impede their performance as surgical biomaterials. To overcome these challenges, we developed a system where chemical gelation was controlled by a conjugate Michael addition between thiol and acrylate in aqueous media, with 97% monomer conversion and 6 wt.% sol fraction. The hydrogel exhibited syneresis on equilibration, reducing to 59.7% of its initial volume. It had mechanical properties similar to soft human tissue with an elastic modulus of 189.8 kPa. Furthermore, a mesh size of 6.9 nm resulted in sustained release of methylprednisolone sodium succinate with a loading efficiency of 2 mg/mL. Functionalization with 50 μg/mL of an oligolysine peptide resulted in attachment of freshly isolated murine mesenchymal stem cells. The rational design of the physical, chemical and biological properties of the hydrogel makes it a potentially promising candidate for injectable applications.