Ectopic induction of cartilage and bone by water-soluble proteins from bovine bone using a collagenous delivery vehicle

Abstract

A controlled-release delivery vehicle for water-soluble osteogenic proteins from demineralized bone matrix was constructed using purified type I collagen. The water-soluble proteins were isolated from a 4 M GdnHCl extract of bone matrix. Although the water-soluble proteins were capable of inducing cartilage formation in vitro, they were incapable of inducing cartilage or bone in vivo when implanted intramuscularly into mice in the absence of an appropriate delivery vehicle. The collagen-based delivery vehicle alone was also incapable of inducing osteogenesis in vivo. However, when the water-soluble proteins were incorporated into the delivery vehicle, the combination was capable of inducing cartilage and bone 76% of the time. These results demonstrate that it is possible to formulate a controlled-release delivery vehicles for soluble bioactive factors which upon release interact with local responsive cells.

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing

“…Such studies have been elusive partly because of a lack of sterile implantable devices that were capable of controlled release. Lyophilized matrices of MC and CMC, containing PLGA microspheres loaded with rhBMP-2, have been suggested and partially tested as 1 such implant type [16][17][18][19][20][21][22][23][24][25][26]. That work was unable to show statistically significant increases in new bone growth because of the presence of rhBMP-2.…”

“…Clinical use of rhBMP-2 has been hampered by a lack of suitable systems for its delivery. Such systems should be capable of maintaining the protein in situ for sufficient time for it to interact with target cells, release the protein at effective concentrations during bone formation, cause no unnecessary tissue distress, and be resorbed [ 23]. Among many systems investigated, biodegradable spheres of poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and the copolymer poly(lactide-co-glycolide) (PLGA) have been selected because they are bioerodible but not toxic or tissue reactive.…”

Calvarial bone response to a tricalcium phosphate-genipin crosslinked gelatin composite

“…The most exciting potential role of this composite is as a carrier of bone inductive agents, such as demineralized bone matrix or bone morphogenetic protein [31][32][33]. It has been found that when the osteoinductive agent is used alone, it would not promote bone formation [34]. If there is no carrier to contain the bone morphogenetic protein, it will diffuse before the formation of new bone.…”

Acceleration of Alveolar Ridge Augmentation Using a Low Dose of Recombinant Human Bone Morphogenetic Protein-2 Loaded on a Resorbable Bioactive Ceramic

“…(17)(18)(19)(20). The most widely used carrier is the absorbable collagen sponge (ACS) which has structural strength insufficient to maintain a space for new bone formation.…”