Award Title: Investigation of the correlation between bone-defect healing and the mechanical loads occurring in biomimetic 3D-printed bone scaffolds – towards better design of implants to repair large bone defects
Funder: The Academy of Medical Sciences

Abstract: Background: 
Bone defects are caused by trauma or bone-tumour removal. When the defect is large or occurring in a weight-bearing bone, incomplete healing after surgical reconstruction is likely. 
Artificial 3D-printed porous scaffolds can be osteoconductive, osteoinductive and large enough to bridge critical-size defects, and allow patient- and defect-specific customisation. Their manufacturing techniques permit the control of their mechanical properties so that they resemble the host bone, which is crucial for avoiding shielding leading to bone loss. Porous scaffolds have hence shown a promising capability to facilitate rapid healing of large bone defects.
Jeffers and colleagues (Addit Manuf J 22; Biomaterials 194; Appl Mater Today 15) have recently 3D-printed non-degradable biomimetic bone scaffolds from titanium and polyamide (stiffness larger than or similar to that of trabecular bone, respectively), and implanted them into cylindrical defects in sheep femura in vivo. Micro-CT and histological slices acquired six weeks post-surgery revealed directional bone growth into the entire length of the scaffold. The researchers concluded that scaffold stiffness compliance with the host bone is vital for bone regeneration, and that implant permanence is essential for its structural role of bearing loads through bone healing.
Objectives:
We hypothesise that osteogenesis on the scaffold struts correlates with the mechanical loads acting in the struts. Accordingly, the aim of the proposed project is to employ in-silico modelling to calculate the mechanical loads (strains and stresses) occurring within 3D-printed bone scaffolds bridging critical-size defects in sheep femura, while exploiting the imaging data already acquired (i.e., without actual use of animals). The analysis outputs will be used to study potential correlation between osteogenesis and loads in the scaffold struts. These data will identify the ranges of scaffold and bone-tissue loads promoting osteogenesis, which will be utilised in the design of scaffolds allowing transfer of loads encouraging ‘optimal’ bone formation and regeneration.
Methods:
The in-vivo experiments previously conducted in the visit institution will be recreated in silico.
The available pre-operative CT scans of each sheep femur will be segmented to create a 3D geometrical model. A detailed model of each scaffold will be generated from the drawings used to manufacture it. A large defect will be virtually created in the mid diaphysis of the femur, and the scaffold will be implanted into the defect to mimic the in-vivo surgical procedure. 
Inhomogeneous mechanical properties will be assigned to the bone based on the density of each bone voxel as depicted in the CT scans.
Physiological loading conditions will be derived from the literature.
A commercial finite-element solver will be used to calculate the loads occurring within the scaffold and host bone.
All computational simulations will be juxtaposed with the equivalent micro-CT images obtained post-operatively. Correlations between the scaffold loads and the rate and spatial pattern of osteogenesis on the scaffold struts will be examined.
An iterative optimisation procedure of adjusting the architectural features of the scaffold, and employing the computational simulations to explore the effects of these adjustments on the scaffold loads to be transferred to the forming bone, will be followed.


Research Activity Codes: 5.3 MEDICAL DEVICES;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health Categories: MUSCULOSKELETAL