Arai, Yoshie Park, Hyoeun Park, Sunghyun Kim, Dohyun Baek, Inho Jeong, Lipjeong Kim, Byoung Ju Park, Kwideok Lee, Dongwon Lee, Soo-Hong 2024-01-19T16:02:00Z 2024-01-19T16:02:00Z 2021-09-02 2020-12 0168-3659 https://pubs.kist.re.kr/handle/201004/117743 A high level of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) upregulates pro-inflammatory cytokines and inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), which are key factors in bone regeneration. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has antioxidant and anti-inflammatory activities and also plays beneficial roles in bone regeneration by stimulating the osteogenic differentiation of MSCs while suppressing their adipogenic differentiation. Despite its remarkable capacity for bone regeneration, multiple injections of UDCA induce adverse side effects such as mechanical stress and contamination in bone defects. To fully exploit the beneficial roles of UDCA, a concept polymeric prodrug was developed based on the hypothesis that removal of overproduced H2O2 will potentiate the osteogenic functions of UDCA. In this work, we report bone regenerative nanoparticles (NPs) formulated from a polymeric prodrug of UDCA (PUDCA) with UDCA incorporated in its backbone through H2O2-responsive peroxalate linkages. The PUDCA NPs displayed potent antioxidant and anti-inflammatory activities in MSCs and induced osteogenic rather than adipogenic differentiation of the MSCs. In rat models of bone defect, the PUDCA NPs exhibited significantly better bone regeneration capacity and anti-inflammatory effects than equivalent amounts of UDCA. We anticipate that PUDCA NPs have tremendous translational potential as bone regenerative agents. English ELSEVIER Bile acid-based dual-functional prodrug nanoparticles for bone regeneration through hydrogen peroxide scavenging and osteogenic differentiation of mesenchymal stem cells Article 10.1016/j.jconrel.2020.09.023 1 JOURNAL OF CONTROLLED RELEASE, v.328, pp.596 - 607 JOURNAL OF CONTROLLED RELEASE 328 596 607 N scie scopus 000600791600043 2-s2.0-85091573935 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article URSODEOXYCHOLIC ACID TAUROURSODEOXYCHOLIC ACID MITOCHONDRIAL-FUNCTION MARROW MECHANISMS NANOMEDICINE ADIPOGENESIS ADIPOSE RATS Bile acid Polymeric prodrug Nanoparticles Hydrogen peroxide Bone tissue regeneration Mesenchymal stem cells