Challenges in skeletal tissue engineering

Title : Challenges in skeletal tissue engineering

Abstract:

Skeletal tissues, bone and cartilage, do not regenerate in humans. While bone fractures can repair themselves, critical size bone defects do not, nor does the avascular cartilage. Hence, repair of these tissues is often achieved using autologous grafts. This, however, can result in donor site morbidity. Therefore, the possibility of stimulating effective regenerative responses as observed in certain lower vertebrates and early in development, or of engineering skeletal tissues for grafting with similar properties to native ones, has generated extensive interest over the years. Notwithstanding some significant advances, neither approach has yet resulted in the establishment of effective standard clinical procedures, and engineering skeletal tissue still presents many challenges. They include identifying the most suitable stem/progenitor cells and 3-dimensional (3D) structures to support their skeletogenic differentiation and maturation as well as provide appropriate biomechanical properties. Different properties of bone and cartilage and requirements to generate them in a dish will be discussed in the context of our work aimed at repairing craniofacial birth defects, with a particular focus on ear cartilage. Differences in profile and differentiation potential of human mesenchymal stem cells from different sources under different culture and 3D conditions (e.g. self-assembly, scaffolds, bioprinting) will be highlighted. Significantly, we have shown that a POSS-PCL-fibrin scaffold seeded with human adipose tissue-derived stem cells leads to the formation of organized bone similar histologically and structurally to native paediatric calvarial bone, and able to support vascularization. In contrast, all the progenitor/stem cells we have studied appear to differentiate more efficiently into cartilage when allowed to self-organize than when encased in different scaffolds tested.

Biography:

Patrizia Ferretti is Professor of Regenerative Biology at UCL Great Ormond Street Institute of Child Health, London, UK. She studied at Pisa University and at the Mario Negri Institute for Pharmacological Research, Milan, Italy, prior to moving to the Max Planck Institute, Goettingen, Germany, and then to London. She is interested in mechanisms governing tissue repair within the context of normal and abnormal development of the nervous system and of craniofacial structures.Over the years her group has made a sustained and internationally recognized contribution to the regeneration field. They have identified a number of cellular and molecular mechanisms which play a role in response to injury and repair and established models to study human diseases using stem/progenitor cells. Current work focused on engineering skeletal tissue and modelling human rare diseases using stem cells continues to implement the successful strategy of addressing basic biological questions and harnessing the information acquired to develop therapeutic approaches.