Hypoxia inducible factor regulating scaffolds for osteochondral regeneration

Acute cartilage lesions, which can cause disability and progress osteoarthritis , are a significant clinical problem. The poor self-hearing capacity of the cartilage has prompted strategies to repair damaged articulating surfaces with surgically-implantable, engineered osteochondral constructs that provide a fill thickness repair that seamlessly fuses with the subchondral bone. A major hurdle in creating engineered osteochondral tissue is in replicating the distinct microenvironmets of bone and cartilage in a single continuous construct. This interdisciplinary project takes a new approach to osteochondral regeneration by engineering materials that mimic the native osteochondral tissue by spatially controlling the cellular regulation of oxygen via hypoxia inducing factor (HIF) stabilisation. Our objective will be to utilise PEGDA/hyaluronan-based hydrogels, tissue-specific growth factors and of human mesenchymal stem cells (MSC) in a single, continuous construct. We will then use a combination of biological and materials engineering methods to assess region-specific bone and cartiliage tissue formation. Translational aspects will include testing constructs in an osteochondral defect in a small animal model. We aim to deliver a new tissue engineering strategy for osteochondral regeneration by mimicking the microenvironmental conditions of native tissue, particularly oxygen pressure, to develop successful therapies to treat cartilage lesions. An ambitious versatile student will gain skills i MSC isolation and culture, qRT-PCR, histochemical and immunostaining techniques, microCT, Raman spectroscopy and small animal surgery. Objectives: year1/2-incorporate HIF mimetic gradient into scaffolds, Year2/3-demonstrate osteochondral tissue reformation in vitro, Year3/4-animal model surgery and evaluation of healing.