Bone loss caused by stress shielding of metallic implants is a concern, as it can potentially lead to long-term implant failure. Surface coating and reducing structural stiffness of implants are two ways to improve bone ingrowth and osteointegration. Additive manufacturing, through selective laser sintering (SLS) or electron beam melting (EBM) of metallic alloys, can produce porous implants with bone ingrowth regions that enhance osteointegration and improve clinical outcomes. Histology of porous Ti6Al4V plugs of two pore sizes with and without electrochemically deposited hydroxyapatite coating, implanted in ovine condyles, showed that bone formation did not penetrate deep into the porous structure, whilst significantly increased bone growth along coated pore surfaces (osteointegration) was observed. Finite Element simulations, combining new algorithms to model bone ingrowth and the effect of surface modification on osteoconduction, were verified with the histology results. The results showed stress shielding of porous implants made from conventional titanium alloy due to material stiffness and implant geometry, limiting ingrowth and osteointegration. Simulations for reduced implant material stiffness predicted increased bone ingrowth. For low modulus Titanium-tantalum alloy (Ti-70%Ta), reduced stress shielding and enhanced bone ingrowth into the porous implant was found, leading to improved mechanical interlock. Algorithms predicted osteoconductive coating to promote both osteointegration and bone ingrowth into the inner pores when they were coated. These new Finite Element algorithms show that using implant materials with lower elastic modulus, osteoconductive coatings or improved implant design could lead to increased bone remodelling that optimises tissue regeneration, fulfilling the potential of enhanced porosity and complex implant designs made possible by additive layer manufacturing techniques.

Understanding how bone adapts to mechanical stimuli is fundamental for optimising treatments against musculoskeletal diseases in preclinical studies, but the contribution of physiological loading to bone adaptation in mouse tibia has not been quantified so far. In this study, a novel mechanistic model to predict bone adaptation based on physiological loading was developed and its outputs were compared with longitudinal scans of the mouse tibia. Bone remodelling was driven by the mechanical stimuli estimated from micro-FEA models constructed from micro-CT scans of C57BL/6 female mice (N = 5) from weeks 14 and 20 of age, to predict bone changes in week 16 or 22. Parametric analysis was conducted to evaluate the sensitivity of the models to subject-specific or averaged parameters, parameters from week 14 or week 20, and to strain energy density (SED) or maximum principal strain (ε maxprinc ). The results at week 20 showed no significant difference in bone densitometric properties between experimental and predicted images across the tibia for both stimuli, and 59% and 47% of the predicted voxels matched with the experimental sites in apposition and resorption, respectively. The model was able to reproduce regions of bone apposition in both periosteal and endosteal surfaces (70% and 40% for SED and ε maxprinc , respectively), but it under-predicted the experimental sites of resorption by over 85%. This study shows for the first time the potential of a subject-specific mechanoregulation algorithm to predict bone changes in a mouse model under physiological loading. Nevertheless, the weak predictions of resorption suggest that a combined stimulus or biological stimuli should be accounted for in the model.

Additive manufactured, porous bone implants have the potential to improve osseointegration and reduce failure rates of orthopaedic devices. Substantially porous implants are increasingly used in a number of orthopaedic applications. HA plasma spraying-a line of sight process-cannot coat the inner surfaces of substantially porous structures, whereas electrochemical deposition of calcium phosphate can fully coat the inner surfaces of porous implants for improved bioactivity, but the osseous response of different types of hydroxyapatite (HA) coatings with ionic substitutions has not been evaluated for implants in the same in vivo model. In this study, laser sintered Ti6Al4V implants with pore sizes of Ø 700 μm and Ø 1500 μm were electrochemically coated with HA, silicon-substituted HA (SiHA), and strontium-substituted HA (SrHA), and implanted in ovine femoral condylar defects. Implants were retrieved after 6 weeks and histological and histomorphometric evaluation were compared to electrochemically coated implants with uncoated and HA plasma sprayed controls. The HA, SiHA and SrHA coatings had Ca:P, Ca:(P+Si) and (Ca+Sr):P ratios of 1.53, 1.14 and 1.32 respectively. Electrochemically coated implants significantly promoted bone attachment to the implant surfaces of the inner pores and displayed improved osseointegration compared to uncoated scaffolds for both pore sizes (p<0.001), whereas bone ingrowth was restricted to the surface for HA plasma coated or uncoated implants. Electrochemically coated HA implants achieved the highest osseointegration, followed by SrHA coated implants, and both coatings exhibited significantly more bone growth than plasma sprayed groups (p�0.01 for all 4 cases). SiHA had significantly more osseointegration when compared against the uncoated control, but no significant difference compared with other coatings. There was no significant difference in ingrowth or osseointegration between pore sizes, and the bone-implant-contact was significantly higher in the electrochemical HA than in SiHA or SrHA. These results suggest that osseointegration is insensitive to pore size,