Abstract
Oxygen deficiency resulting from bone fracture-induced vascular disruption leads to massive cell death and delayed osteoblast differentiation, ultimately impairing new bone formation and fracture healing. Enhancing local tissue oxygenation can help promote bone regeneration. In this work, an injectable composite oxygen-generating system consisting of calcium peroxide (CaO2)/manganese dioxide (MnO2)-encapsulated poly lactic-co-glycolic acid (PLGA) microparticles (CaO2 + MnO2@PLGA MPs) is proposed for the local delivery of oxygen. By utilizing a series of methodologies, the impacts of each component used for MP fabrication on the oxygen release behavior and cytotoxicity of the CaO2 + MnO2@ PLGA MPs are thoroughly investigated. Our analytical data obtained from in vitro studies indicate that the optimized CaO2 + MnO2@PLGA MPs developed in this study can effectively relieve the hypoxia of preosteoblast MC3T3-E1 cells that are grown under low oxygen tension and promote their osteogenic differentiation, thus holding great promise in enhancing fractural healing by increasing tissue oxygenation.
Highlights
Bone fracture is one of the most common injuries of the musculoskeletal system (Claes et al, 2012)
To address the abovementioned issues, we present an innovative implantable composite oxygen-generating system that can be delivered by local injection, and characterize its function in relieving cellular hypoxia and promoting osteogenic differentiation (Figure 1A)
Together with the previous results, these findings suggest that the developed CaO2 + MnO2@poly lactic-co-glycolic acid (PLGA) MPs can be utilized to enhance the oxygenation and in vitro osteogenic differentiation of preosteoblasts under low oxygen tension
Summary
Bone fracture is one of the most common injuries of the musculoskeletal system (Claes et al, 2012). As oxygen is required in several basic cellular processes that are crucial for fracture healing (Lu et al, 2013), tissue hypoxia resulting from vascular disruption during fracture leads to cell death and delayed osteoblast differentiation, impairing new bone formation and fracture healing (Lu et al, 2013; Gómez-Barrena et al, 2015). To address this issue, autologous bone grafts can be harvested and transplanted to the defect site to promote bone regeneration owing to their endogenous high-density vasculature, which can quickly anastomose with surrounding blood vessels (Zheng et al, 2010; Lee and Volpicelli, 2017). A sustained oxygen delivery strategy that can be used to improve local oxygen tension is warranted
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