The influence of collagen and hyaluronan matrices on the delivery and bioactivity of bone morphogenetic protein-2 and ectopic bone formation.
Bone morphogenetic protein-2 (BMP-2) is known to enhance fracture healing when delivered via a bovine collagen sponge. However, collagen rapidly releases BMP-2 with a high burst phase that is followed by a low sustained phase. As a result, supra-physiological doses of BMP-2 are often required to successfully treat bone defects. High BMP-2 dosing can introduce serious side effects that include edema, bone overgrowth, cyst-like bone formation and significant inflammation. As the release behavior of BMP-2 carriers significantly affects the efficacy of fracture healing, we sought to compare the influence of two BMP-2 delivery matrices with contrasting release profiles on BMP-2 bioactivity and ectopic bone formation. We compared a thiol-modified hyaluronan (Glycosil™) hydrogel that exhibits a low burst followed by a sustained release of BMP-2 to a collagen sponge for the delivery of three different doses of BMP-2, the bioactivities of released BMP-2 and ectopic bone formation. Analysis of bone formation by micro-computed tomography revealed that low burst followed by sustained release of BMP-2 from a hyaluronan hydrogel induced up to 456% more bone compared to a BMP-2 dose-matched collagen sponge that has a high burst and sustained release. This study demonstrates that BMP-2 released with a low burst followed by a sustained release of BMP-2 is more desirable for bone formation. This highlights the therapeutic potential of hydrogels, particularly hyaluronan-based, for the delivery of BMP-2 for the treatment of bone defects and may help abrogate the adverse clinical effects associated with high dose growth factor use.
['Bhakta|Gajadhar|G|', 'Lim|Zophia X H|ZX|', 'Rai|Bina|B|', 'Lin|Tingxuan|T|', 'Hui|James H|JH|', 'Prestwich|Glenn D|GD|', 'van Wijnen|Andre J|AJ|', 'Nurcombe|Victor|V|', 'Cool|Simon M|SM|']
D000818:Animals D001672:Biocompatible Materials D055396:Bone Morphogenetic Protein 2 D001842:Bone and Bones D002417:Cattle D002460:Cell Line D003094:Collagen D016503:Drug Delivery Systems D005260:Female D006820:Hyaluronic Acid D020100:Hydrogels D051379:Mice D009999:Ossification, Heterotopic D019919:Prosthesis Implantation D051381:Rats D017207:Rats, Sprague-Dawley D011994:Recombinant Proteins D016212:Transforming Growth Factor beta D055114:X-Ray Microtomography
Collagen sponge Hydrogel Glycosaminoglycan Osteogenesis Release kinetics