Advantages of our tissue-engineered ACL substitute •Produced within 2 weeks •Anchored in culture •Matrix remodeling in vivo post-grafting •No immune rejection •Avoid tissue morbidity •Implantation by arthroscopy (no scar) •Applications: •Human •Animal •In vitro model •Other ligament (tooth, etc.) Improvement of our tissue-engineered ACL substitute We could use: •A stronger (acellular?) scaffold •A scaffold anchored with synthetic bone plugs •A scaffold made of collagen fibers modified through nanotechnology •A scaffold containing a biosensor to alert the athlete at knee joint limit range of movement during training post-surgery These are some potential improvements to be developed. Nanomedical Biological Device in development Collagens -Comprised of polypeptide chains (alpha chains), eich in proline and hydroxyproline, that form a unique triple-helical structure that is 300 nanometers long; -Each a-chain has a repeating amino acid structure of Gly-Xaa of 1.5 nanometers in diameter; -There are more than 20 collagen types that exist in animal tissue; Collagens -Comprised of polypeptide chains (alpha chains), eich in proline and hydroxyproline, that form a unique triple-helical structure that is 300 nanometers long; -Each a-chain has a repeating amino acid structure of Gly-Xaa of 1.5 nanometers in diameter; -There are more than 20 collagen types that exist in animal tissue; Potential applications in nanotechnology In clinical context, human collagens would be preferred over bovine collagens because the material isolated from cows can prompt an unwanted immune response in patients and it can harbor animal pathogens that might infect humans. This work may also establish the basis for applications in nanotechnology. Collagens -Five types are known to form fibers: Types I, II, III, V, and XI. -These types tend to self-assemble into periodic, cross-striated fibers, which can reach centimeters in length and tens of microns in diameter. -Type I collagen: the predominant fiber-forming collagen type, found in bones, skin, teeth, and tendons. -Type II collagen: the second most abundant, found in cartilaginous tissue, developing cornea, and vitreous humor. Potential applications in nanotechnology In the context of nanotechnology, collagen can be seen as a type of nanowire because it is thin and long. Coated with metallic ions, human collagens could form the basis of implantable electric sensors. By attaching certain biological molecules to the wire, it would be possible to create sensors that might, for example, quickly alert a diabetic to falling insulin levels. Potential applications in nanotechnology We are currently developing the synthesis of human types I, II and III recombinant collagens to use them for tissue engineering, biomedical and nanotechnology applications. Various types of human collagen in vitro, produced the baculovirus system that involves sf9 insect cells, will be available in our laboratory to develop new scaffolds that promote connective tissue repair and regeneration in vivo post-implantation. Bovine type I collagen scaffold Lyophilized and rehydrated © F.G./LOEX Thank you! To the co-researchers: Dr. Réjean Cloutier, orthopedic surgeon, Université Laval, Québec; Dr. Jean Lamontagne, orthopedic surgeon, Université Laval, Québec; Dr. Nazrul Islam, in memoriam; To our graduate students: Mrs Ioana Diana Napa, M.Sc. Mr. Pierrot Tremblay, M.Sc. Mrs Anne-Marie-Belzil, M.Sc. Mrs Lina Maria Robayo, M.Sc. Thank you to our collaborators! Dr. Sheila Laverty, Fac. Vet Med., Université de Montréal; Dr. Bertrand Lussier, Fac. Vet Med., Université de Montréal; Dr. Marc D. McKee, Fac. Med., McGill University; Dr. Robin Poole, Fac. Med., McGill University And others… Thank you so much! Conference Co-Chairs: Martine Rothblatt, Ph.D. Présidente directrice générale, Unither Biotech, Inc. Baruch S. Blumberg, M.D., Ph.D. Senior Advisor to the President, Fox Chase Cancer Center Temple C. Fortson, Editorial Assistant to the Chairman & CEO United Therapeutics Corporation Jenesis A. Rothblatt Assistant Manager of Conferences & Virtual Worlds United Therapeutics Corporation