The novel bone-targeted agents were designed and synthesized by the combination of raloxifene and bisphosphonates. The anti-osteoporosis effect was evaluated by bone mineral density (BMD) obtained from OVX mice in viv...The novel bone-targeted agents were designed and synthesized by the combination of raloxifene and bisphosphonates. The anti-osteoporosis effect was evaluated by bone mineral density (BMD) obtained from OVX mice in vivo. The results indicated that the compound 8, 9 not only prevented ovariectomy induced loss of bone but also enhanced BMD to 0.87% and 19.67% compared to Sham, respectively.展开更多
Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,...Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and retention.To tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone regeneration.We encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore sizes.The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation assays.The PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo.The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect animal.Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.展开更多
Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival o...Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite （HA） and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.展开更多
文摘The novel bone-targeted agents were designed and synthesized by the combination of raloxifene and bisphosphonates. The anti-osteoporosis effect was evaluated by bone mineral density (BMD) obtained from OVX mice in vivo. The results indicated that the compound 8, 9 not only prevented ovariectomy induced loss of bone but also enhanced BMD to 0.87% and 19.67% compared to Sham, respectively.
基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSIT)(Nos.2020R1C1C1005830 and 2021R1C1C2095130)supported by the Bio&Medical Technology Development Program of the National Research Foundation(NRF)and funded by the Korean government(MSIT)(No.2022M3A9F3082330).
文摘Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and retention.To tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone regeneration.We encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore sizes.The PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation assays.The PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in vivo.The PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect animal.Our findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.
基金financially supported by the National Natural Science Foundation of China (Nos. 31600811, 81573154, 81773432)the Application Fundamental Research Foundation of Sichuan Province Science and Technology Department, China (Nos. 2016JY0157, 2017JY0123)Scientific Research Foundation of the Health and Family Planning Commission of Sichuan Province, China (Nos. 17PJ556, 17PJ563)
文摘Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite （HA） and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.
