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.

Sintering effects on chemical and physical properties of bioactive ceramics

The objective of this study was to characterize the chemical and physical properties of bioactive ceramics prepared from an aqueous paste containing hydroxyapatite(HA)and beta tri-calcium phosphate(β-TCP).Prior to formulating the paste,HA andβ-TCP were calcined at 800℃and 975℃(11 h),milled,and blended into 15%/85%HA/β-TCP volume-mixed paste.Fabricated cylindrical rods were subsequently sintered to 900℃,1100℃or 1250℃.The sintered specimens were characterized by helium pycnometry,X-ray diffraction(XRD),Fourier transform-infrared(FT-IR),and inductively coupled plasma(ICP)spectroscopy for evaluation of porosity,crystalline phase,functional-groups,and Ca:P ratio,respectively.Mechanical properties were assessed via 3-point bending and diametral compression.Qualitative microstructural evaluation using scanning electron microscopy(SEM)showed larger pores and a broader pore size distribution(PSD)for materials sintered at 900℃and 1100℃,whereas the 1250℃samples showed more uniform PSD.Porosity quantification showed significantly higher porosity for materials sintered to 900℃and 1250℃(p<0.05).XRD indicated substantial deviations from the 15%/85%HA/β-TCP formulation following sintering where lower amounts of HA were observed when sintering temperature was increased.Mechanical testing demonstrated significant differences between calcination temperatures and different sintering regimes(p<0.05).Variation in chemical composition and mechanical properties of bioactive ceramics were direct consequences of calcination and sintering.