Ya Ren,Weiqing Kong,Yihao Liu,Xue Yang,Xiang Xu,Lei Qiang,Xuelian Mi,Changru Zhang,Haoyi Niu,Chengwei Wang,Jinwu Wang
Bone defect repair remains a major clinical challenge that requires the construction of scaffolds that can regulate bone homeostasis. In this study, a photo-cured mesoporous bioactive glass (PMBG) precursor is developed as a tricalcium phosphate (TCP) agglomerant to obtain a double-phase PMBG/TCP scaffold via 3D printing. The scaffold exhibits multi-scale porous structures and large surface areas, making it a suitable carrier for the loading of parathyroid hormone (PTH) (1-34), which is used for the treatment of osteoporosis. In vitro and in vivo results demonstrate that PMBG/TCP scaffolds coordinated with PTH (1-34) can regulate bone homeostasis in a bidirectional manner to facilitate bone formation and inhibit bone resorption. Furthermore, bidirectional regulation of bone homeostasis by PTH (1-34) is achieved by inhibiting fibrogenic activation protein (FAP). Thus, PMBG/TCP scaffolds coordinated with PTH (1-34) are viable materials with considerable potential for application in the field of bone regeneration and provide an excellent solution for the design and development of clinical materials.
Insufficient bone formation and excessive bone resorption caused by estrogen deficiency are the major factors resulting in the incidence of postmenopausal osteoporosis (PMOP). The existing drugs usually fail to re-establish the osteoblast/osteoclast balance from both sides and generate side-effects owing to the lack of bone-targeting ability. Here, engineered cell-membrane-coated nanogels PNG@mR&C capable of scavenging receptor activator of nuclear factor-κB ligand (RANKL) and responsively releasing therapeutic PTH 1–34 in the bone microenvironment are prepared from RANK and CXCR4 overexpressed bone mesenchymal stem cell (BMSC) membrane-coated chitosan biopolymers. The CXCR4 on the coated-membranes confer bone-targeting ability, and abundant RANK effectively absorb RANKL to inhibit osteoclastogenesis. Meanwhile, the release of PTH 1–34 triggered by osteoclast-mediated acid microenvironment promote osteogenesis. In addition, the dose and frequency are greatly reduced due to the smart release property, prolonged circulation time, and bone-specific accumulation. Thus, PNG@mR&C exhibits satisfactory therapeutic effects in the ovariectomized (OVX) mouse model. This study provides a new paradigm re-establishing the bone metabolic homeostasis from multitargets and shows great promise for the treatment of PMOP.
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