Regulation of hypoxic stress and oxidative stress in bone grafting: Current trends and future perspectives

Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells, growth factors and scaffolds. However, the intra/peri-implant region is exposed to se-vere hypoxic stress and oxidative stress during the early stage of implantation with bone graft materials, which endangers the survival, proliferation and differentiation of seed cells within the implants as well as the host cells surrounding the implants. If the bone graft material could spontaneously and intelligently regulate the hypoxic stress and oxidative stress to a moderate level, it will facilitate the vascularization of the implants and the rapid regeneration of the bone tissue. In this review, we will first introduce the signaling pathways of cellular response under hypoxic stress and oxidative stress, then present the clas-sical material designs and examples in response to hypoxic stress and oxidative stress. And finally, we will address the important role of epigenetic mechanisms in the regulation of hypoxic stress and oxida-tive stress and describe the potential applications and prospective smart bone graft materials based on novel epigenetic factors against hypoxic stress and oxidative stress in bone repair. The main content of this review is summarized in the following graphical abstract.(c) 2023 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )