Osteochondral tissue engineering using novel 3D printed scaffolds and multi-layered cell sheet technology

点击翻译按钮获取中文摘要

Osteochondral tissue damage or loss is one of the most common diseases due to traumatic injuries, natural degradation of cartilaginous tissue with aging, arthritis or surgery. These clinical situations encompass serious damage to not only articular cartilage but also the underlying calcified subchondral bone. The conventional therapeutic approaches include autografts, allografts, stimulation of bone marrow and debridement. Autografts have limited stock and allografts are associated with the risk of immune rejection or disease transmission, while bone marrow stimulation treatments are only palliative and not completely curative. Therefore, the ability to treat osteochondral defects is a major clinical need. Over the last decades, tissue engineering approaches have been utilised for regenerating articular cartilage. However the output of these is still not satisfactory. Part of the reason may be due to the unique and complex structure of articular cartilage (e.g. it does not have blood vessels, lymphatics and nerves, but it is under a biomechanical environment). Over the last a few years, researchers have suggested that a healthy subchondral bed plays a key role for the success of cartilage tissue regeneration. In this project, a multidisciplinary approach will be utilised to combine material science, mechanical engineering (Dr Xiaodong Jia) with stem cell biology (Dr Jiang) for osteochondral tissue engineering (Dr Yang). The multi-layered cell sheet (MLCS) technology, in close collaboration with Tokyo Women's Medical University under a formal collaborative agreement, allows us to harvest intact cell sheet with minimum damage to the cells and maximum retention of cell-cell junctions, extracellular matrix and growth factors embedded in the matrix. This technology could be useful for stem cell handling and the development of novel collagen scaffolds to mimic natural structure of articular cartilage. Previously we have showed the potential of using epigenetic approaches to control stem cell function without change the genome. A novel histone deacetylase inhibitors (HDACi), MI192 will be used for the pre-treatment of human MSCs to enhance their osteogenic differentiation potential for new bone formation. The combination of the bone phase and cartilage phase will provide a novel solution for repair/restoration of osteochondral defect in clinical relevant animal models.The aim of this project is to develop a novel natural collagen scaffold and combine these scaffolds with 3D printed scaffolds, epigenetic modified stem cells as well as multi-layered cell sheet technology for osteochondral tissue engineering in vitro and in vivo.The project fits very well within EPSRC's Healthcare and Technologies Theme - Developing Future Therapies. The objectives include:A) Development of novel collagen scaffolds using MLCS technology.B) Fabricate cartilage phase in vitro using epigenetic modified stem cell, MLCS technology, novel collagen scaffolds.C) Fabricate bone phase in vitro using epigenetic modified stem cell, MLCS technology and PepGEN P-15 enhanced 3D printed porous polymer scaffold (in collaboration Otago University, UCL and University of Manchester).D) Osteochondral tissue engineering in vivo using the bone and cartilage constructs formed above.MLCS technology is a novel engineering method.A novel natural collagen scaffolds will be developed with unique architecture similar to natural articular cartilage, which could be patentable.A combination of MLCS technology, novel collagen scaffolds and 3D printed polymer scaffolds will provide a novel approach for complex tissue engineering.