Abstract
Abstract Immobilizing a single growth factor such as rhBMP-2 on Implant materials can significantly increase the integration of implants into bone in animals. Paradoxically the effective osteoinductive dose of rhBMP-2 in humans is ca. 100-1000-fold higher than in animals and may induce serious side effects in spine fusion surgery. In physiological bone healing at least 10 separate growth and differentiation factors are sequentially involved in the first two healing phases leading to a callus and/or woven bone. It is therefore hypothesized that a significant dose reduction for rhBMP-2 applications in humans may be achieved by a combination of rhBMP-2 with other growth factors in a biomimetically oriented manner. Some aspects involved in multimodal bioactive hybrid carriers with spatio-temporal release kinetics and a new phenomenon ("protein interference") are presented.
Highlights
State-of-the-art immobilization of a single growth factor such as bone morphogenetic protein 2 on Implant materials can significantly increase the integration of implants in bone in animals [1,2]
A necessary dose reduction for rhBMP-2 applications in humans may be achieved by a combination of rhBMP-2 with a second essential mediator such as vascular endothelial growth factor
RhBMP-2 and rhVEGF165 prepared in E. coli, according to [8] and [9] respectively, were from Morphoplant GmbH, Bochum) and radioactively labeled by the iodine monochloride method, i.e. 125I-BMP-2, 125I-VEGF, according to [10,11]
Summary
State-of-the-art immobilization of a single growth factor such as bone morphogenetic protein 2 (rhBMP-2) on Implant materials can significantly increase the integration of implants in bone in animals [1,2]. A necessary dose reduction for rhBMP-2 applications in humans may be achieved by a combination of rhBMP-2 with a second essential mediator such as vascular endothelial growth factor (rhVEGF165). In physiological secondary bone healing at least 10 different growth and differentiation factors are involved in the first two healing phases leading to a callus and/or woven bone. To this end a new generation of bi- or multimodal bioactive hybrid carriers with specific temporal or spatial release kinetics for each factor is our engineering aim e.g. to release rhVEGF with a shorter half-life than rhBMP-2, based on the physiological bone healing time-scale. RhBMP-2- and VEGF-containing foamed tablets or electrospun fleeces have shown sustained release half-lives ranging between 85 and 350 days
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