ANGIOSCAFF · Angiogenesis-inducing Bioactive and Bioresponsive Scaffolds in Tissue Enginering

Angiogenesis underlies almost all biological processes of morphogenesis, including those in tissue repair and regeneration. Physiological angiogenesis is controlled by a complex interplay between cells and their environment: the extracellular matrix (ECM) provides signaling via numerous ECM adhesion molecules and growth factors bound to ECM polysaccharide components; and cells locally degrade and remodel the ECM to create pores into which angiogenic endothelial cells migrate. This observation, that physiological angiogenesis proceeds in response to solid-phase cues motivates our approach, namely creating bioactive resorbable materials as scaffolds that contain bound molecular signals to induce physiological angiogenesis in situations of tissue repair and regeneration. In some of our scaffold materials, porosity is inherent by virtue of fabrication, and in others porosity is created by cell-associated proteolysis as it is in physiological angiogenesis. All materials will be designed so as to be injectable or implantable into the human body. In some work, the final injectable/implantable material will comprise only materials and bioactive biomolecular signals, and in other cases it will also comprise cells. Thus, the concept of ANGIOSCAFF is to create materials that are bioresponsive (to environmental signals including pH and redox potential, and to cellular signals such as proteases), that are bioactive (by virtue of bound peptide or recombinant protein adhesion ligands and bound and releasable growth factors), and that are capable of carrying cellular therapeutics. To realize ANGIOSCAFF, we have assembled a team comprising both industrial and academic expert groups in biomaterials design and development, experts in the science and application of angiogenesis, in imaging in animal models, and in applications demanding biomaterials-based, angiogenesis-demanding tissue engineering therapies, including repair of bone, skin, cardiac muscle, skeletal muscle and nerve.