Proximal humerus fractures are the third most common fractures in the over-65 patient population and their stable fixation remains a key challenge in orthopaedic and trauma surgery. While Open Reduction Internal Fixation by plate has become a well-known treatment modality in the last few decades, clinical studies associate high complication rate with its use. The overall aim of this project was to create a computer-aided design framework for proximal humerus plates using a validated subject-specific humerus-plate finite element model. The framework consisted of three stages: (1) reverse engineering of bone and plate geometry, (2) creation and validation of a finite element model simulating the in vitro testing of the bone-implant construct and (3) parametric optimisation study of implant design using this model. In vitro biomechanical tests were conducted to not only compare the mechanical performance of three key commercially available proximal humerus plates (S3-, Fx- and PHILOS plate) but also the effect of different screw zones. Sixty-five humeri specimens with two-part surgical neck fractures were treated and grouped based on their different screw configurations. Extension, flexion, varus and valgus bending were applied in the cantilever fashion in the elastic tests whereas only varus bending was applied in the plastic tests. The load required to apply 5 mm displacement was measured to determine bone-plate construct stiffness. The S3 plate yielded the stiffest constructs and while the removal of the inferomedial support had the most impact on varus bending stiffness, type of medial support was important: inferomedial screws in the Fx plate achieved higher bending stiffness than blade insertion. Stability of constructs treated with the plate was an interplay of factors such as the plateâs and screws' number, orientation and position. Next, a subject-specific finite element model of the humerus-plate construct was successfully developed that simulated the stiffest of the constructs from the in vitro varus bending tests conducted in this project. The model was validated against the in vitro results. The validated model was then used to perform a parametric optimisation study where the combination of design parameters (height and divergence angle of S3 plateâs inferomedial screws) was determined that achieved optimum bone-plate construct stability (minimum fracture gap change). Out of the 538 designs tested, the optimum design (16o divergence angle and 33o height angle) yielded the lowest fracture gap change (0.156 mm) which was 4.686% lower than the standard finite element model while achieving 5.707% higher varus bending load (54.753 N). The validated model was also used to investigate the issue of using smooth pegs and threaded screws. Twenty-six models with different percentages of screw threading were run to compare their bone-plate construct stiffness. While threading the smooth pegs was found to increase the varus bending stiffness by up to 4.546%, it did not affect all screws equally. Finally, the successful completion of the optimisation study of screw orientation and the clinical investigation promises the implementation of the computational framework for a range of future multi-objective optimisation studies of multiple design parameters especially for the design of implants for other parts of the human body and also for investigations into other clinically relevant questions.