Three-dimensional biomaterial degradation - Material choice, design and extrinsic factor considerations.

The apparent difficulty to precisely control fine-tuning of biomaterial degradation has initiated the recent paradigm shift from conventional top-down fabrication methods to more nature-inspired bottom-up assemblies. Sophistication of material fabrication techniques allows today's scientists to reach beyond conventional natural materials in order to synthesise tomorrow's 'designer material'. Material degradation into smaller components and subsequent release of encapsulated cells or cell-signalling agents have opened medically exploitable avenues, transforming the area of regenerative medicine into a dynamic and self-propagating branch of modern medicine. The aim to synthesise ever more refined scaffolding structures in order to create micro- and nanoenvironments resembling those found in natural tissues now represents an ever growing niche in the materials sciences. Recently, we have developed and conducted the world's first in-human tracheal transplantation using a non-degradable completely synthetic biomaterial. Fuelled by such clinical potential, we are currently developing a biodegradable version suitable for skin tissue engineering and paediatric applications. However, despite enormous efforts, current, as yet insurmountable challenges include precise biomaterial degradation within pre-determined spatial and temporal confines in an effort to release bio-signalling agents in such orchestrated fashion as to fully regenerate functioning tissues. In this review, the authors, almost anti-climactically, ask the readers to step out of the artificially over-constructed spiral of ever more convoluted scaffold fabrication techniques and consider the benefits of controllable bottom-up scaffold fabrication methods. It will further be investigated how scaffold designs and fabrication methods may influence degradation and subsequent release of incorporated elements. A focus will be placed on the delivery of growth factors, stem cells and therapeutic agents alone or in parallel. The difficulties of designing a delivery vehicle capable of delivering multiple factors whilst maintaining distinct release kinetics will be highlighted. Finally, this review will be rounded off with an insight into current literature addressing the recurring issues of degradation product toxicities and suggests means of overcoming those.