Bone graft compositions with improved growth factor stability

A - Human Necessities – 61 – L

Patent

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A61L 27/00 (2006.01) A61L 27/22 (2006.01) A61L 27/36 (2006.01) A61L 27/50 (2006.01) A61L 27/54 (2006.01) A61L 27/58 (2006.01) A61F 2/28 (2006.01) A61F 2/30 (2006.01)

Patent

CA 2433038

An improved demineralized bone matrix (DBM) or other matrix composition is provided that has been mixed with a stabilizing agent that acts as (1) a diffusion barrier, (2) a enzyme inhibitor, (3) a competitive substrate, or (4) a masking moiety. A diffusion barrier acts as a barrier so as to protect the osteoinductive factors found in DBM from being degraded by proteolytic and glycolytic enzymes at the implantation site. Stabilizing agents may be any biodegradable material such as starches, modified starches, cellulose, dextran, polymers, proteins, and collagen. As the stabilizing agents degrades or dissolves in vivo, the osteoinductive factors such as TGF-.beta., BMP, and IGF are activated or exposed, and the activated factors work to recruit cells from the preivascular space to the site of injury and to cause differentiation into bone-forming cells. The invention also provides methods of preparing, testing, and using the inventive improved osteoinductive matrix compositions.

L'invention concerne une matrice osseuse déminéralisée (DBM) ou autre composition matricielle améliorée mélangée avec un agent stabilisant pour agir comme: 1) barrière de diffusion; 2) inhibiteur d'enzymes; 3) substrat compétitif; ou 4) fragment de masquage. Une barrière de diffusion agit comme une barrière pour empêcher la dégradation des facteurs ostéoinductifs présents dans la DBM par des enzymes protéolytiques ou glycolytiques au niveau du site d'implantation. Les agents stabilisants peuvent être n'importe quel matériau biodégradable, tel que des amidons, des amidons modifiés, de la cellulose, du dextrane, des polymères, des protéines, ou du collagène. A mesure que les agents stabilisants se dégradent ou se dissolvent <i>in vivo</i>, les facteurs ostéoinductifs, tels que TGF-.beta., BMP et IGF, sont activés ou exposés, et les facteurs activés travaillent à recruter des cellules de l'espace prévasculaire au site de la lésion et à causer la différenciation en cellules de formation osseuse. L'invention concerne en outre des méthodes de préparation, d'essai et d'utilisation des compositions matricielles ostéoinductives améliorées.

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