Synthetic hydrogel scaffold is an effective vehicle for delivery of INFUSE (rhBMP2) to critical-sized calvaria bone defects in rats.
Medtronic's INFUSE Bone Graft provides surgeons with a potent tool for stimulating bone formation. Current delivery vehicles that rely on Absorbable Collagen Sponges (ACS) require excessive quantities of the active ingredient in INFUSE, recombinant human Bone Morphogenic Protein-2 (rhBMP2), to achieve physiologically relevant concentrations of the growth factor, driving up the cost of the product and increasing the likelihood of undesirable side effects in neighboring tissues. We demonstrate that a simple light-mediated, thiol-ene chemistry can be used to create an effective polymer delivery vehicle for rhBMP2, eliminating the use of xenographic materials and reducing the dose of rhBMP2 required to achieve therapeutic effects. Comprised entirely of synthetic components, this system entraps rhBMP2 within a biocompatible hydrogel scaffold that is degraded by naturally occurring remodeling enzymes, clearing the way for new tissue formation. When tested side-by-side with ACS in a critical-sized bone defect model in rats, this polymeric delivery system significantly increased bone formation over ACS controls.
Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
Peter D
PD
Mariner
Justin M
JM
Wudel
David E
DE
Miller
E Erin
EE
Genova
Sven-Olrik
SO
Streubel
Kristi S
KS
Anseth
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000493:pharmacokinetics*; D016025:Bone Transplantation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D017102:Fracture Healing / Q000187:drug effects; D005781:Gelatin Sponge, Absorbable / Q000493:pharmacokinetics; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D012886:Skull / Q000187:drug effects* / Q000601:surgery; D054457:Tissue Scaffolds
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate