Introduction: Contemporary reconstructive approaches for critical-sized bone defects carry significant disadvantages. As a result, clinically driven research has focused on the development and translation of alternative therapeutic concepts. Scaffold guided tissue regeneration (SGTR) is an emerging technique to heal critical-sized bone defects. However, issues synchronising scaffold vascularisation with bone-specific regenerative processes currently limit bone regeneration for extra-large (XL, 19cm3) critical-sized bone defects. To address this issue, we developed a large animal model that incorporates a corticoperiosteal flap (CPF) for sustained scaffold neo-vascularisation and bone regeneration. Methodology: A pre-clinical evaluation using a 3D-printed medical-grade ε-polycaprolactone b-tricalcium phosphate (mPCL-TCP) scaffold combined with a cortico-periosteal flap (CPF) was undertaken in ten sheep with a medium (M, 9.5 cm3) volume segmental defect of the tibia. Results: In ten sheep the efficacy of this approach for healing M volume segmental bone defects was demonstrated by plain radiography, micro-computed tomography, scanning electron microscopy, immunohistochemical and histological analysis. Furthermore, in two sheep we demonstrate how this approach can be safely extended to heal XL critical- size defects. Conclusion: This study presents an original CPF technique in a clinically relevant and well described pre-clinical model which can be used in conjunction with the SGTR concept to address challenging critical-sized bone defects in vivo.