Importance of delivery systems for growth-stimulatory factors in combination with osteopromotive membranes. An experimental study using rhBMP-2 in rat mandibular defects

Abstract

This study was undertaken to investigate whether the choice of carrier/delivery system might be crucial for rhBMP-2 induced osteogenesis beneath osteopromotive membranes. Standardized 5-mm transosseous rat mandibular defects were implanted with recombinant human BMP-2 (rhBMP-2) with or without membrane placement. Two doses of rhBMP-2 (1 microg and 8 microg per defect) were delivered with either collagen sponge or bioabsorbable poly(D,L-lactide-coglycolide) (PLA/PGA) beads plus allogenic blood as carriers. Membrane-covered defects (no BMP) served as controls. Virtually all defects treated with rhBMP-2 without membrane placement already were bridged by new bone after 12 days, independent of rhBMP-2 dose or carrier material, and lateral bone growth was extensive outside the original defect. Membrane placement significantly decreased the stimulatory activity of the BMP, as seen after 12 days, even though osteogenesis was more advanced with rhBMP-2 and membrane compared to membrane alone. After 24 days, defects treated with membrane and rhBMP-2 in the PLA/PGA carrier were totally bridged with regenerated bone, whereas defects covered with membrane without BMP implantation displayed an average bone bridging of only 53%. In an overall analysis of the bone regeneration, the PLA/PGA carrier material was found to be superior to the collagen carrier in the presence of membranes, which was, in turn, more efficient than membrane placement alone (no rhBMP-2). There was much less lateral bone growth when BMP implantation was combined with membrane placement. It was concluded that bone formation beneath osteopromotive membranes may be significantly enhanced by rhBMP-2 and that the delivery system can affect the amount of bone formation obtained. For eventual clinical use, membrane placement has the advantage of keeping the growth-stimulatory implant in place as well as obtaining the desired anatomical contour of the bone formed.

Recombinant Biglycan Promotes Bone Morphogenetic Protein-induced Osteogenesis

“…The surgical procedures were performed as previously described (Zellin and Linde, 1997;Miguez et al, 2011). Briefly, 5-mm critical-sized defects were generated in mandibles of SpragueDawley male rats via a trephine bur.…”

Histomorphometric analysis of rat alveolar wound healing with hydroxyapatite alone or associated to BMPs

“…Currently, fifteen amino acid sequences are known, with the most active in humans being BMP-2, BMP-4, and BMP-7 (7). Even though there is no doubt about the advantages of BMPs in bone neoformation (8,9), recent studies are directed to techniques that allow BMPs release in adequate concentrations to encourage bone neoformation, which seems to be related to the physical and chemical properties of the vehicle. In spite of the tendency to use the collagen sponge as a vehicle (10), other vehicles deserve more study.…”

Evaluation of the Bone Repair Capacity and the Cytotoxic Properties of a Particular Xenograft: An Experimental Study in Rats

“…[15][16][17] The common reason is to establish a better grafting material which can be used for regeneration and filling of the bone defects. To our knowledge, the xenografts have osteoconductive properties ensuring bone ingrowth into grafted materials.…”