Angioscaff confirms its success in year 3 with more breakthrough developments for regenerative therapeutics
1 February 2012
Austria
Angioscaff is a major collaboration initiative funded by the 7th framework programme of the European Commission. Coordinated by Professor Jeffrey Hubbell from the Ecole Polytechnique de Lausanne, the partnership brings together more than 30 groups from leading European and Israeli academic centres, small industries and large pharmaceutical companies.
Nature has provided us with an exceptional mechanism of wound healing and repair after injury. Healing starts with the formation of a fibrinogen blood clot acting as a support for re-building a new functional tissue. However there are two major problems associated with this natural scarring process. The first one is that the standard blood clot dissolves too rapidly, giving too little time for the normal repair process to take place and allowing connective, dysfunctional tissue to invade the site of injury. The second problem is the excess of inflammation that can occur in response to the injury. Angioscaff is developing radical new scaffolds, biomaterials and tissue engineering strategies for the regeneration of bone, skin, skeletal muscle, the cardiovascular, peripheral vascular and central nervous systems.
Now entering its 4rth and final year, the Angioscaff consortium has confirmed its on going success in the early stage development of regenerative therapeutics this year with more than 20 peer reviewed publications, 2 patents filed and 1 company created. Here are some of the major advances the consortium has produced.
One of the most notable achievements of the past year was a collaborative work performed between the labs of Jeff Hubbell, Dror Seliktar, Erella Livne and Sabine Eming and published in Science translational medicine. The group engineered a multifunctional recombinant fragment of fibronectin allowing the sequestration of several growth factors simultaneously and promoting synergistic signaling between Growth factor signaling and Integrins. They pieced together two fibronectin fragments (the 9th to 10th and the 12th to 14th type III fragments) to control Integrin and growth factor binding, respectively. The resulting fragment was covalently immobilized on a fibrin scaffold and was able to bind VEGF, PDFF and BMP, three factors involved in skin and bone repair. The resulting recombinant fibronectin fragment was then tested in vivo in 2 models: a model of impaired wound healing in a diabetic mice to test for its skin regeneration capacity and in a critical-size bone defect rat model to test for its bone regeneration effect. In both cases, the growth factor efficiency in tissue repair was dramatically improved. Enhanced re epithelialization, granulation tissue formation and angiogenesis were noted for the wounds. For the bone defects, an increased bone tissue deposition and recruitment of bone progenitor cells was reported. These results are very promising for the use of the FN III-910/12-14 modified matrices in humans to heal chronic wounds and repair bones. Further testing in larger animal models will be the next step before translation.
The group of Andrea Banfi has established how angiogenesis could be induced in skeletal muscle in vivo by the controlled release of VEGF. The group used a fibrin gel but modulated the gel stiffness by adding aprotinin to maximizing the persistence of the biomaterial in vivo. Gels were also loaded with various concentrations of VEGF. The group tested various concentrations of the two components by injection of the various hydrogels in mouse muscle and evaluated angiogenesis histologically. This way, they determined an optimum combination inducing a normal angiogenesis without the formation of enlarged vessels. These results establish that aprotinin and VEGF together determine the rate of VEGF release in vivo and the potency of the angiogenic stimulus.
The Werner lab has developed a conjugation technique allowing for in situ polymerization and cell encapsulation within Star-PEG-heparin hydrogels. This technique allows for the incorporation of various cell responsive factors to both the heparin and the Star-PEG moiety, generating a multifunctional hydrogel and independent delivery of growth factor delivery. Using this technique, Human vein endothelial cells (HUVECs) were encapsulated in a Star-PEG gel in which the heparin was functionalized with a constant level of cyclic RGD to bind integrin. The group first showed that the gelation procedure was non-toxic and then studied the angiogenic effects of soft and stiff forms of such hydrogels when loaded with different concentrations of VEGF. They established that the viability and cell morphology of the primary HUVECs were improved by VEGF loading, with the most beneficial influence found for soft gels, pointing out the superior role of a soft environment for promoting HUVEC network formation.
Notes to editors:
About Angioscaff
ANGIOSCAFF creates bio-responsive, bioactive and injectable materials capable of carrying therapeutics, which can be used for tissue regeneration in humans. The work has been divided into seven interlocking but distinct strategic areas. The specific strategies being implemented are: (1) Radical innovations in state-of-the-art biomaterials (2) Design and production of advanced bioactive scaffolds enabling internal growth of tissue and the site specific delivery of bioactive signaling factors, that control cell differentiation (3) Injectable biomaterials and effective delivery device design that can induce angiogenesis in the body (4) Development of bioresorbable, highly porous, and structurally sound tissue-engineered scaffolds (5) Functionalized biomaterials that have direct influence on cell behavior (6) Bioactive scaffolds with broad applicability for complex tissues Coordinator: Jeffrey Hubbell, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
Contacts:
Angioscaff Consortium Manager
Jonathan Dando, PhD
Dando, Weiss & Colucci Ltd
dandojonathan@hotmail.com
Project’s Coordinator
Professor Jeffrey Hubbell
Ecole polytechnique de Lausanne
Jeffrey.hubbell@epfl.ch
Nature has provided us with an exceptional mechanism of wound healing and repair after injury. Healing starts with the formation of a fibrinogen blood clot acting as a support for re-building a new functional tissue. However there are two major problems associated with this natural scarring process. The first one is that the standard blood clot dissolves too rapidly, giving too little time for the normal repair process to take place and allowing connective, dysfunctional tissue to invade the site of injury. The second problem is the excess of inflammation that can occur in response to the injury. Angioscaff is developing radical new scaffolds, biomaterials and tissue engineering strategies for the regeneration of bone, skin, skeletal muscle, the cardiovascular, peripheral vascular and central nervous systems.
Now entering its 4rth and final year, the Angioscaff consortium has confirmed its on going success in the early stage development of regenerative therapeutics this year with more than 20 peer reviewed publications, 2 patents filed and 1 company created. Here are some of the major advances the consortium has produced.
One of the most notable achievements of the past year was a collaborative work performed between the labs of Jeff Hubbell, Dror Seliktar, Erella Livne and Sabine Eming and published in Science translational medicine. The group engineered a multifunctional recombinant fragment of fibronectin allowing the sequestration of several growth factors simultaneously and promoting synergistic signaling between Growth factor signaling and Integrins. They pieced together two fibronectin fragments (the 9th to 10th and the 12th to 14th type III fragments) to control Integrin and growth factor binding, respectively. The resulting fragment was covalently immobilized on a fibrin scaffold and was able to bind VEGF, PDFF and BMP, three factors involved in skin and bone repair. The resulting recombinant fibronectin fragment was then tested in vivo in 2 models: a model of impaired wound healing in a diabetic mice to test for its skin regeneration capacity and in a critical-size bone defect rat model to test for its bone regeneration effect. In both cases, the growth factor efficiency in tissue repair was dramatically improved. Enhanced re epithelialization, granulation tissue formation and angiogenesis were noted for the wounds. For the bone defects, an increased bone tissue deposition and recruitment of bone progenitor cells was reported. These results are very promising for the use of the FN III-910/12-14 modified matrices in humans to heal chronic wounds and repair bones. Further testing in larger animal models will be the next step before translation.
The group of Andrea Banfi has established how angiogenesis could be induced in skeletal muscle in vivo by the controlled release of VEGF. The group used a fibrin gel but modulated the gel stiffness by adding aprotinin to maximizing the persistence of the biomaterial in vivo. Gels were also loaded with various concentrations of VEGF. The group tested various concentrations of the two components by injection of the various hydrogels in mouse muscle and evaluated angiogenesis histologically. This way, they determined an optimum combination inducing a normal angiogenesis without the formation of enlarged vessels. These results establish that aprotinin and VEGF together determine the rate of VEGF release in vivo and the potency of the angiogenic stimulus.
The Werner lab has developed a conjugation technique allowing for in situ polymerization and cell encapsulation within Star-PEG-heparin hydrogels. This technique allows for the incorporation of various cell responsive factors to both the heparin and the Star-PEG moiety, generating a multifunctional hydrogel and independent delivery of growth factor delivery. Using this technique, Human vein endothelial cells (HUVECs) were encapsulated in a Star-PEG gel in which the heparin was functionalized with a constant level of cyclic RGD to bind integrin. The group first showed that the gelation procedure was non-toxic and then studied the angiogenic effects of soft and stiff forms of such hydrogels when loaded with different concentrations of VEGF. They established that the viability and cell morphology of the primary HUVECs were improved by VEGF loading, with the most beneficial influence found for soft gels, pointing out the superior role of a soft environment for promoting HUVEC network formation.
Notes to editors:
About Angioscaff
ANGIOSCAFF creates bio-responsive, bioactive and injectable materials capable of carrying therapeutics, which can be used for tissue regeneration in humans. The work has been divided into seven interlocking but distinct strategic areas. The specific strategies being implemented are: (1) Radical innovations in state-of-the-art biomaterials (2) Design and production of advanced bioactive scaffolds enabling internal growth of tissue and the site specific delivery of bioactive signaling factors, that control cell differentiation (3) Injectable biomaterials and effective delivery device design that can induce angiogenesis in the body (4) Development of bioresorbable, highly porous, and structurally sound tissue-engineered scaffolds (5) Functionalized biomaterials that have direct influence on cell behavior (6) Bioactive scaffolds with broad applicability for complex tissues Coordinator: Jeffrey Hubbell, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
Contacts:
Angioscaff Consortium Manager
Jonathan Dando, PhD
Dando, Weiss & Colucci Ltd
dandojonathan@hotmail.com
Project’s Coordinator
Professor Jeffrey Hubbell
Ecole polytechnique de Lausanne
Jeffrey.hubbell@epfl.ch