ABSTRACT
Local delivery of rhBMP-2 is a clinically proven strategy for bone regeneration [1-4]. Collagen, which is the primary protein component of bone, is an effective carrier for rhBMP-2 due to its biocompatibility and ability to bind rhBMP-2 [5]. The U.S. Food and Drug Administration (FDA) has approved the use of rhBMP-2 delivered on an absorbable collagen sponge (sold commercially as INFUSE® Bone Graft by Medtronic Sofamor Danek) for posterolateral lumbar fusion, grafting fractures of the tibial mid-diaphysis, sinus lift procedures, and alveolar ridge augmentations [6]. Considering recent reports that rhBMP-2 promotes bone healing as well as autograft [7], it has become a common standard of care for treating severe fractures. The bolus release of rhBMP-2 from collagen [1,8] recruits local osteoprogenitor cells and initiates osteogenesis [9]. However, the majority of the rhBMP-2 is released
CONTENTS
7.1 Introduction ................................................................................................ 107 7.2 Recombinant Human Growth Factors .................................................... 108
7.2.1 Recombinant Human Fibroblast Growth Factor (rhFGF) ........ 108 7.2.2 Platelet-Derived Growth Factor (rhPDGF) ................................. 109 7.2.3 Vascular Endothelial Growth Factor (rhVEGF) ......................... 111 7.2.4 Combinations with rhBMP-2 ........................................................ 112 7.2.5 Summary ......................................................................................... 115
7.3 Statins .......................................................................................................... 115 7.3.1 Drug Delivery Strategies .............................................................. 116 7.3.2 Regeneration of Craniomaxillofacial Bone Defects .................. 116 7.3.3 Regeneration of Orthopedic Bone Defects ................................. 118 7.3.4 Summary ......................................................................................... 120
7.4 Conclusions ................................................................................................. 120 References ............................................................................................................. 121
in the first few days [10], which has been associated with the need to deliver supra-physiological doses of rhBMP-2 to induce a robust osteogenic effect. Rapidly released rhBMP-2 may diffuse from the fracture site prior to significant infiltration of osteoprogenitor cells into the scaffold [1]. Furthermore, rapid release of the drug may result in complications such as inflammation and ectopic bone formation [11,12].
