Biomaterial scaffolds are used in bone tissue engineering for promoting new bone regeneration and stabilising the facture bone. An ideal biomaterial scaffold for healing load-bearing large bone defects should have cortical bone matching mechanical properties and osteogenic properties for promoting new bone regeneration. Scaffolds possessing these two traits currently do not exist. The aim of this project is to produce 3D printed scaffolds combined with engineered human blood gels to obtain osteogenic scaffolds with mechanical properties matching cortical bone.
Current scaffolds made of bioactive glasses, bioceramics and their composites have only achieved mechanical properties in the cancellous bone range. Cortical bone is approximately an order of magnitude stronger than cancellous bone. Metals, such as titanium, are widely used in orthopaedic surgeries where high mechanical properties are sought. However, they are much stiffer than bone. The Young’s modulus of titanium is approximately 10 times of cortical bone. This mismatch in mechanical properties shields the physiological stresses from the surrounding bone, which weakens them and makes them prone to fracture over time. Therefore, scaffolds matching human cortical bone mechanical properties are urgently needed.
Potent osteogenic biomolecules such as bone morphogenic protein 2 (BMP2) are now widely used in various orthopaedic surgeries such as treating non-union fractures. However, the supraphysiological dosage used in clinic has caused various complications such as uncontrolled excessive bone growth and cancer. This has prompted researchers to investigate other means to enhance osteogenesis.
Human beings have evolved to fully heal bone fractures at small scales. This process is triggered and regulated by the Regenerative Hematoma/Clot (RHC), which comprises a rich source of endogenous factors and cell populations that are critical for stem/progenitor cell recruitment, immunomodulation, osteogenic differentiation, and ultimate bone healing. However, the RHC is often disturbed or removed during fracture reduction, internal fixation, and debridement in orthopaedic surgeries, leading to poor bone regeneration. Rebuilding the RHC in bone fractures using the patient’s own blood could potentially overcome major current limitations in fracture treatment and enable personalized regenerative implants that are low in cost, easily deployable, and low risk to patients compared to stem cell therapies or bone marrow aspiration.
The specific objectives of this project are:
1. Develop a 3D printing process to fabricate scaffolds with mechanical properties close to human cortical bone. Test the mechanical properties of the printed scaffolds with tuneable architectural parameters.
2. Engineer blood gels with tuneable mechanical properties. Co-printing of scaffolding materials and blood gel.
3. Test in vitro osteogenic differentiation of bone marrow stem cells in the scaffolds.
Training on the methodologies that will be utilised in the project will be provided to the PhD candidate. The main methods include: extrusion-based 3D printing, fabrication of blood gels using self-assembling techniques and human blood, cell culture and characterisation of in vitro osteogenic differentiation.
The student will be co-supervised by Dr Jing Yang and Prof Alvaro Mata in the School of Pharmacy. The studentship will provide for full-time Home tuition fees, an annual stipend, in line with UKRI minimum stipend rates (£15,609 per annum 2021/22 entry). The studentships will run for 42 months from 1 October 2022.
The School of Pharmacy is ranked 5th in the world in the 2021 and 2022 QS World Rankings for pharmacy and pharmacology. The School came joint 1st in the UK on quality of research for Pharmacy Schools in the 2014 Research Excellence Framework and is the only School of Pharmacy to have 100% of research at 4* in the 'Impact on Society’ category.
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