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Synergistic anti-inflammatory and osteogenic n-HA/resveratrol/chitosan composite microspheres for osteoporotic bone regeneration

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Bioactive Materials 2021年第5期6卷 1255-1266页

作者： Limei Li Mali Yu Yao Li Qing Li Hongcai Yang Meng Zheng Yi Han Di Lu Sheng Lu Li Gui Yunnan Key Laboratory of Stem Cell and Regenerative Medicine Science and Technology Achievement Incubation CenterKunming Medical UniversityKunming650500China Department of Stomatology The First People’s Hospital of Yunnan ProvinceKunming650032China Department of Neurology The First Affiliated HospitalKunming Medical UniversityKunming650000China Yunnan Key Laboratory of Digital Orthopaedics Department of OrthopaedicsThe First People’s Hospital of Yunnan ProvinceKunming650032China Department of Endocrinology The Third People’s Hospital of Yunnan ProvinceKunming650011China

The development of functional materials for osteoporosis is ultimately required for bone remodeling.However,grafts were accompanied by increasing pro-inflammatory cytokines that impaired bone formation.In this work,nano-hydroxyapatite(n-HA)/resveratrol(Res)/chitosan(CS)composite microspheres were designed to create a beneficial microenvironment and help improve the osteogenesis by local sustained release of Res.Study of in vitro release confirmed the feasibility of n-HA/Res/CS microspheres for controlled Res release.Notably,microspheres had anti-inflammatory activity evidenced by the decreased expression of pro-inflammatory cytokines TNF-α,IL-1βand iNOS in RAW264.7 cells in a dose dependent manner.Further,enhanced adhesion and proliferation of BMSCs seeded onto microspheres demonstrated that composite microspheres were conducive to cell growth.The ability to enhance osteo-differentiation was supported by up-regulation of Runx2,ALP,Col-1 and OCN,and substantial mineralization in osteogenic medium.When implanted into bone defects in the osteoporotic rat femoral condyles,enhanced entochondrostosis and bone regeneration suggested that the n-HA/Res/CS composite microspheres were more favorable for impaired fracture healing.The results indicated that optimized n-HA/Res/CS composite microspheres could serve as promising multifunctional fillers for osteoporotic bone defect/fracture treatment.

关键词： n-HA/Res/CS microsphere Anti-inflammation Osteo-differentiation osteoporotic bone regeneration

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Mn-containing bioceramics inhibit osteoclastogenesis and promote osteoporotic bone regeneration via scavenging ROS

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Bioactive Materials 2021年第11期6卷 3839-3850页

作者： Jianmei Li Cuijun Deng Wanyuan Liang Fei Kang Yun Bai Bing Ma Chengtie Wu Shiwu Dong Department of Biomedical Materials Science School of Biomedical EngineeringThird Military Medical University(Army Medical University)Chongqing400038China State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai200050China State Key Laboratory of Trauma Burnsand Combined InjuryThird Military Medical University(Army Medical University)Chongqing400038China

Osteoporosis is caused by an osteoclast activation mechanism.People suffering from osteoporosis are prone to bone defects.Increasing evidence indicates that scavenging reactive oxygen species(ROS)can inhibit receptor activator of nuclear factorκB ligand(RANKL)-induced osteoclastogenesis and suppress ovariectomy-induced osteoporosis.It is critical to develop biomaterials with antioxidant properties to modulate osteoclast activity for treating osteoporotic bone defects.Previous studies have shown that manganese(Mn)can improve bone regeneration,and Mn supplementation may treat osteoporosis.However,the effect of Mn on osteoclasts and the role of Mn in osteoporotic bone defects remain unclear.In present research,a model bioceramic,Mn-containedβ-tricalcium phosphate(Mn-TCP)was prepared by introducing Mn intoβ-TCP.The introduction of Mn intoβ-TCP significantly improved the scavenging of oxygen radicals and nitrogen radicals,demonstrating that Mn-TCP bioceramics might have antioxidant properties.The in vitro and in vivo findings revealed that Mn^(2+)ions released from Mn-TCP bioceramics could distinctly inhibit the formation and function of osteoclasts,promote the differentiation of osteoblasts,and accelerate bone regeneration under osteoporotic conditions in vivo.Mechanistically,Mn-TCP bioceramics inhibited osteoclastogenesis and promoted the regeneration of osteoporotic bone defects by scavenging ROS via Nrf2 activation.These results suggest that Mn-containing bioceramics with osteoconductivity,ROS scavenging and bone resorption inhibition abilities may be an ideal biomaterial for the treatment of osteoporotic bone defect.

关键词： Mn-containing bioceramics Antioxidant biomaterials Osteoclastogenesis ROS osteoporotic bone regeneration

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A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration

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生物活性材料(英文) 2023年第1期19卷 75-87页

作者： Lingbin Che Ying Wang Dongyong Sha Guangyi Li Ziheng Wei Changsheng Liu Yuan Yuan Dianwen Song Department of Orthopedics Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai200080PR China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry and School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237PR China Shanghai Advanced Research Institute Chinese Academy of SciencesShanghai201210PR China

Osteoporosis is one of the most disabling consequences of aging,osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths,indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance.Teriparatide is strong bone formation promoter effective in treating osteoporosis,while side effects limit clinical applications.Traditional drug delivery is lack of sensitive and short-term release,finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge.Thus,bioinspired by the natural bone components,we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules,achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand.Herein,biomimetic bone microstructure of mesoporous bioglass,a near-infrared ray triggered switch,thermosensitive liposomes based on a valve,and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration.Teriparatide is pulsatile released from intelligent delivery,not only rejuvenating osteoporotic bone defect,but also presenting strong systemic anti-osteoporosis therapy.This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

关键词： Precise pulsatile release Teriparatide Smart delivery osteoporotic bone regeneration

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