Enzyme-medicated modification of fibrin for tissue engineering

Details Enzyme-medicated modification of fibrin for tissue engineering Enzyme-medicated modification of fibrin for tissue engineering

C - Chemistry, Metallurgy

07

K

C07K 17/00 (2006.01) A61K 38/17 (2006.01) A61K 38/36 (2006.01) A61L 24/10 (2006.01) A61L 27/00 (2006.01) A61L 27/22 (2006.01) A61L 31/00 (2006.01) A61L 31/04 (2006.01) C07K 14/47 (2006.01) C12N 5/00 (2006.01) A61F 2/00 (2006.01)

Patent

CA 2307954

The invention provides fibrin-based, biocompatible materials useful in promoting cell growth, wound healing, and tissue regeneration. These materials are provided as part of several cell and tissue scaffolding structures that provide particular application for use in wound-healing and tissue regenerating. Methods for preparing these compositions and using them are also disclosed as part of the invention. A variety of peptides may be used in conjunction with the practice of the invention, in particular, the peptide IKVAV, and variants thereof. Generally, the compositions may be described as comprising a protein network (e.g., fibrin) and a peptide having an amino acid sequence that comprises a transglutaminase substrate domain (e.g., a factor XIIIa substrate domain) and a bioactive factor (e.g., a peptide or protein, such as a polypeptide growth factor), the peptide being covalently bound to the protein network. Other applications of the technology include their use on implantable devices (e.g., vascular graphs), tissue and cell scaffolding. Other applications include use in surgical adhesive or sealant, as well as in peripheral nerve regeneration and angiogenesis.

L'invention concerne des matières biocompatibles à base de fibrine utiles pour stimuler la croissance cellulaire, la cicatrisation de lésions et la régénération des tissus. Ces matières se présentent sous la forme d'une partie de plusieurs structures d'échaffaudage cellulaire et tissulaire permettant une application particulière destinée à être utilisée dans la cicatrisation des lésions et la régénération des tissus. L'invention concerne également des procédés de préparation de ces compositions et d'utilisation de celles-ci. On peut utiliser divers peptides dans la pratique de l'invention, notamment le peptide IKVAV, et des variants de celui-ci. D'une manière générale, les compositions peuvent être décrites comme comprenant un réseau protéique (par exemple, de la fibrine) et un peptide ayant une séquence d'acides aminés comprenant un domaine de substrat transglutaminase (par exemple un domaine de substrat de facteur XIIIa) et un facteur bioactif (par exemple un peptide ou une protéine, tel qu'un facteur de croissance polypeptidique), le peptide étant lié de manière covalente au réseau protéique. D'autres applications de la technologie comprennent leur utilisation sur des dispositifs implantables (par exemple des greffes vasculaires), un échaffaudage tissulaire et cellulaire. D'autres applications consistent en l'utilisattion dans un adhésif ou un agent de scellement chirurgical, et la régénération et l'angiogénèse des nerfs périphériques.

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