Resveratrol-loaded nanoplatform RSV@DTPF promote alveolar bone regeneration in OVX rat through remodeling bone-immune microenvironment

Abstract

The reconstruction of alveolar bone defect is essential for periodontal regenerative therapy or subsequent prosthetic/implant therapy, particularly in individuals with systemic diseases, such as osteoporosis. ROS accumulation, coupled with aberrant macrophage polarization, is pivotal in the pathogenesis of osteoporosis and contributes to the disequilibrium between bone and the immune system. Consequently, therapeutic strategies targeting the immune microenvironment present a promising approach to the treatment of in situ alveolar bone regeneration in osteoporotic condition. Herein, we present a novel nano platform denoted as RSV@DTPF, designed to target macrophage and facilitate the controllable release of resveratrol in a ROS-responsive behavior. This approach aims to modulate the tampered immune microenvironment. The conjugated folate moiety selectively interacts with the folate receptors expressed on the macrophage surface, thereby augmenting cellular uptake. While the thioketal bond would break down when sensing a high level of intracellular ROS and release the encapsulated RSV. In vitro experiments suggested that designated nanoparticles could scavenge ROS effectively and restore the M1/M2 ratio in a lipopolysaccharide (LPS) -stimulated inflammation environment; The co-culture experiment provided evidence substantiating the adeptness of the modified immune milieu in fostering osteoblast differentiation, while concurrently impeding osteoclast maturation. Furthermore, through comprehensive imaging and histopathological evaluations, we elucidate the potential of RSV@DTPF in promoting osteogenesis within a periodontal defect model utilizing ovariectomized (OVX) rats. This in vivo study substantiates the advantageous impact of the nanoplatform on alveolar bone regeneration and its associated immunomodulatory effects. In summary, the RSV@DTPF nanoplatform exhibited the capacity to orchestrate immune microenvironmental shifts and enhance alveolar bone generation ability in osteoporosis and also could be expected to be applied in other biomedical fields associated with redox metabolism imbalance.