Promotion of osteoporotic bone healing by a tannic acid modified strontium-doped biomimetic bone lamella with ROS scavenging capacity and pro-osteogenic effect

The impaired osteogenic ability and excessive accumulation of reactive oxygen species (ROS) under osteoporosis severely weaken repair performance of biomimetic bone grafts. Currently, biomimetic bone grafts, capable of highly simulating bone hierarchy, could remarkably promote bone regeneration without systemic disease. Decorating biomimetic bone grafts with bioactivities without compromising hierarchical biomimicry stands as a feasible approach to treat the osteoporotic bone defect. Herein, through mineralizing decellularized collagen lamellae via strontium (Sr)- amorphous calcium phosphate and further modifying with tannic acid (TA), TA modified Sr-doped biomimetic bone lamellae was engineered. The physicochemical properties, ROS scavenging capacity and pro-osteogenic effect on osteoporotic bone marrow mesenchymal stem cells of construct were systemically evaluated. The results showed that TA and Sr can be successfully decorated without impairing the nano- and micro-architecture of biomimetic bone lamellae. The construct not only exhibited a potent and long-standing performance to eliminate ROS, but also effectively fostered the proliferation and osteogenic differentiation of osteoporotic bone marrow mesenchymal stem cells under oxidative stress environment. After implantation in the critical-sized bone defect of osteoporotic rat, it potently facilitated bone regeneration via synergistically activating PI3K/AKT signaling pathway. Hence, this construct is projected to be candidate for further engineering biomimetic bone grafts with more complicated hierarchy for accelerated healing of the osteoporotic bone defect.