Blood vessel growth and development (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 components; and cells locally degrade and remodel the ECM to create pores into which blood vessel forming cells migrate during the growth of new vessels. Under physiological conditions, most of the signaling is provided by the solid phase, whether from the ECM as mentioned above or from contact with other endothelial cells (ECs). This underlying tissue generation is now considered a pivotal component in the regeneration of surrounding tissue. In other words if there is not an underlying network of blood vessels the tissue targeted will not regenerate and the degenerative disease reversed, despite the presence of specialised tissue forming cells.

Degenerative diseases create a life-altering experience for the person with injury, for their partner, parents, siblings, and children. The subsequent dimishment of body functions associated with the diseases can cause depression and loss of self-esteem. It has been considered essential, based on European policy consistent with human rights principles, that people with disabilities should be treated with dignity, encouraged to have independence, be given equality of opportunity, encouraged to have an active participation, a full citizenship and a high quality of life. Given the diversity of degenerative diseases indicated above, pathological manifestation can occur at any age: either as a child, during an individual's most productive years, or as an aged person. The trauma frequently results in morbidity, and as a result, patients typically require continuous physical and medical care depending on the disease, severity of manifesation, degree of disability, and location of injury.

There has been an increased prevalence of degenerative diseases with growing aged population, which has stimulated a growth in the need for biomaterials.

Over the past 50 years, average life expectancy at birth has increased globally by over 20 years, from 46.5 years in 1950-55 to 65.2 years in 2002. Today there are 600 million people in the world aged 60 years or over, and this will double by 2025 and reach 2 billion by 2050. While degenerative diseases are not the exclusive domain of the aged, they do impact this sector of society the highest with subsequent increased social and economic burdens on the health care systems on which they depend.

The impact of AngioScaff on the complete regenerative medicine field is best illustrated by organ transplantion, the major motivation behind regenerative medicine: 25% of patients waiting for an organ donor die before one can be found, and in 2001 there were 12 607 available donors available to help 81 528 patients in need. The stimulation of tissue repair via the use of optimized scaffolds (porous, angiogenic, bioactive and resorbable) that stimulate endogenous cells to regenerate a fully functional tissue should address this problem and decrease related mortality.

The direct healthcare costs of organ replacement are about € 240 billion globally (about 8 percent of global healthcare spending) arising from therapies that keep people alive (such as kidney dialysis), implanted replacement devices, and organ transplants. With a € 240 billion global industry already built on first generation tissue and organ therapy products and substitutes, regenerative medicine has a potential to exceed € 600 billion by 2030.

Bone repair, the dominant clinical and market needs are in spinal fusion and healing of non-union fractures; accelerated repair of traumatic fractures, and accelerated healing after dental surgery. Good progress has already been made in the marketplace in spinal surgery with BMP-2 delivered in a collagen matrix, developed by Wyeth and marketed by Medtronic Sofamor-Danek; adoption in spinal fusion in the USA has been very high (selling more than $2 million/day); however, its very high cost has led to little use in spinal surgery in Europe. This cost is driven by the extraordinarily high amount of therapeutic BMP-2 protein that is included in the formulation – equivalent to the amount present in ~1000 humans per spinal level – pointing to inadequacies in localized release on an optimal time course. It is estimated that annually more than one million patients need treatment for skeletal problems worldwide. As the European population is aging considerably, orthopedic diseases will become a major concern for the forthcoming decades. Thus, even in cases where products have been successfully developed, there exists substantial room for technological improvement. AngioScaff will address such limitations.

Skin wound and soft tissue repair, progress has been made in the discovery of growth factors that can regulate repair, but there remain important challenges. Johnson & Johnson has introduced PDGF-BB to the clinic and marketplace, which costs several k€ and is plagued by very inconvenient dosing. Adoption in both Europe and the USA has been very limited due to these considerations, penetrating less than $150 million/year into a market that is thought to be approximately $5 billion/year deep. It is noteworthy that carboxymethyl cellulose gel carrier has almost no characteristics in common with the native ECM or with the ECM analog matrices that will be developed in AngioScaff. In contrast, AngioScaff’s matrices will provide adequate signaling to induce angiogenesis into chronic wound environments. By attending to the details of cell signaling with matrix-displayed bioactive factors, we will develop more advanced and efficacious therapies for diabetic and venous insufficiency patients.

Growth factor therapies have also made substantial inroads in prevention of dermal scarring. TGF- β3 is being introduced to the marketplace in scar prevention along surgical incision lines with a simple yet effective injection of the growth factor; however, in larger, more complicated wounds like burns, more advanced display and release technologies are required. AngioScaff’s matrices will be developed in this context, with matrix-binding TGF-β3 displayed by bioactive scaffolds.

Cardiac muscle repair, revascularization of cardiac muscle following myocardial infarction remains a very major challenge of enormous socioeconomic value. Cardiovascular disease remains the number one fatality in the world killing 17 million people each year (and 5 million in the EU-25, accounting for 51% of all deaths) with no indication that this figure is decreasing. Long-term morbidity and the high costs of treatments add to the economic impact of cardiovascular disease. Although some progress has been made, more is required since adverse trends continue in major cardiovascular risk factors including obesity and type II diabetes could lead to a doubling in absolute incidence of cardiovascular disease by 2050.  Thus, entirely new therapeutic avenues need to be opened up based not on risk factor modification but on better understanding of and wider intervention in the pathophysiology of the disease.

Some progress has been made with progenitor cell-based therapies, but clinical results are not yet sufficiently compelling to change the standard-of-care. Approaches with bioactive, angiogenesis-inducing scaffolds have the potential to remedy this, delivering both cells and bioactive factors in a bioactive manner to control angiogenesis through local control of cellular behavior.

Skeletal muscle repair in pathologies such as muscular dystrophy remain a major challenge. Throughout the world, musculoskeletal impairments and conditions are the most frequent causes of disability: over 300,000 European citizens suffer from a muscular disorder. Encompassing more than 150 diseases and syndromes, musculoskeletal conditions affect every age group. Progress has been made by direct injection of cells into the diseased muscle, but fundamental hurdles in both signaling to these cells and supporting their metabolic needs remain – challenges that will be addressed by AngioScaff.

Peripheral and central nerve repair, remains one of the greatest challenges of plastic and reconstructive surgery. No bioactive therapies have entered into the marketplace yet, only mechanical approaches such as nerve guidance tubes to prevent encroachment of scar between the proximal and distal stumps of the severed nerve. In spite of much being known about the role of growth factors such as β-NGF, NT-3 and BDNF in neuronal development, practical biomaterials systems have not been developed to translate this knowledge to the clinical marketplace. The use of advanced and bioactive biomaterials that are naturally readsorbed will allow the correct presentation of the growth at the correct dosage for a sufficient amount of time to enable to neural cells to differentiate properly and become functional. This approach could potentially be used to treat Parkinson’s disease (~600,000 cases in Europe), Huntington’s disease (~19,000 cases), and spinal cord injury (~330 000 cases with over 15 000 new cases each year, mostly in males aged 18-25).