An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate.
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.
Pritchard
Christopher D
CD
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. cpritcha@mit.edu
O'Shea
Timothy M
TM
Siegwart
Daniel J
DJ
Calo
Eliezer
E
Anderson
Daniel G
DG
Reynolds
Francis M
FM
Thomas
John A
JA
Slotkin
Jonathan R
JR
Woodard
Eric J
EJ
Langer
Robert
R
D000818:Animals; D002478:Cells, Cultured; D020100:Hydrogels / Q000737:chemistry*; D007267:Injections; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D020100:Hydrogels; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D008776:Methylprednisolone Hemisuccinate