Synergising mechanical and osteogenic properties for personalized bone tissue engineering via co-3D printing with fibre reinforced composite and blood

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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. Current scaffolds made of bioglasses, bioceramics and particle reinforced composites have only achieved mechanical properties in the cancellous bone range. Cortical bone is 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. The adverse effects associated with supraphysiological dosage of BMP2 has led to a FDA warning to a spinal fusion device (Infuse-BMP2 loaded collagen in a titanium cage) and subsequent rejection of similar products. 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 aim of this project is to produce 3D printed continuous fibre reinforced composite scaffolds combined with engineered human blood gels to obtain osteogenic scaffolds with mechanical properties matching cortical bone.The specific objectives are:1. Develop a 3D printing process to fabricate continuous fibre reinforced composite scaffolds. Test the mechanical properties of the printed scaffolds with tuneable architectural parameters.2. Engineer blood gels with tuneable mechanical properties. Co-printing of fibre reinforced composite and blood gel.3. Test in vitro osteogenic differentiation of bone marrow stem cells in blood-composite scaffolds.