Photothermally triggered biomimetic drug delivery of Teriparatide via reduced graphene oxide loaded chitosan hydrogel for osteoporotic bone regeneration

Abstract

Stimuli-responsive biomaterials have attracted more attention in drug delivery area as controlled release with physiologically relevant temporal and spatial context. Teriparatide is used for osteoporosis treatment by systemic administration. Recently, the extending utilization of local biomimetic delivery to repair bone defect provides numerous advantages, for its anabolic effect, maintaining local higher concentration and avoiding side effects. In the present study, we firstly design and propose the concept of Teriparatide time and dose manner on bone marrow mesenchymal stem cells derived from ovariectomized rats (OVX-BMSCs). And the near-infrared (NIR) light responsive, reduced graphene oxide loaded chitosan hydrogel (CS/rGO) films are the fabricated by electrodeposition. The local delivery of Teriparatide, which mimic pulsatile secretion in physiological conditions, is achieved by photothermal conversion. And the osteogenesis and angiogenesis of this delivery system are evaluated in calvarial defect osteoporotic models. And the optimal time and dose manner of Teriparatide is around 1 h*24*10−9 mol L−1(M)/day to 2 h*12*10−9 M/day by evaluating the osteogenic activity on OVX-BMSCs. The micro-computed tomography (Micro-CT) and histological analysis illustrate that NIR light-responsive CS/rGO films achieve a favorable effect for bone regeneration through biomimetic delivery of Teriparatide. Moreover, higher density of blood vessels is observed between the newly formed bone and in the center of defect region. Our research combines physiological pulsatile secretion of Teriparatide with the stimuli-responsive effect of the biomaterial, which provides a novel strategy to improve osteoporotic bone regeneration.