JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Yang Jiao,Haixin Wang,Mingyu Zhao,Huiling Liu,Peng Shen,Gang Wu,Tim Forouzanfar,Franklin R. Tay,Li Miao,Hongchen Liu,Qian Liu
Bone regeneration is a dynamic, multistage process requiring the orchestrated interplay of cellular recruitment, immune modulation, and balanced osteoblast-osteoclast activity. To address this clinical challenge, we developed a nanocomposite hydrogel-based drug delivery system integrating gelatin methacrylate (GelMA) and silk fibroin methacrylate (SFMA) scaffolds containing mesoporous silica nanoparticles (MSNs) for spatiotemporally controlled co-delivery of stromal cell-derived factor-1α (SDF-1α) and osteoprotegerin (OPG). This dual-delivery platform enabled sustained and localized release of immunoregulatory and osteoprotective agents, achieving a synchronized modulation of the regenerative microenvironment. The MSNs functioned as an effective nanocarrier to preserve bioactivity and prolong release kinetics of bioactive factors, while the hydrogel matrix provided structural integrity and protease-responsive degradation matching bone repair dynamics. The system potentiated bone marrow mesenchymal stem cell (BMSC) recruitment, proliferation, and osteogenic differentiation, reprogrammed macrophage polarization toward pro-regenerative M2 phenotypes, and suppressed osteoclastogenesis. In vivo validation using a rat critical-sized femoral defect model revealed accelerated osseous regeneration. Mechanistically, transcriptomic profiling identified concerted PI3K/Akt-MAPK pathway activation. The immunomodulatory hydrogel reduced pro-inflammatory cytokines while elevating osteogenic factors. Crucially, the hydrogel restored osteoblast-osteoclast crosstalk balance, suppressing TRAP + osteoclast formation through OPG-mediated RANKL inhibition. Overall, this hydrogel-based delivery platform demonstrates a clinically translatable strategy for drug-enabled bone regeneration, with precise control over therapeutic release, spatial localization, and immuno-osteogenic coupling.
研究领域:
生物材料学
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再生医学
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骨科
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 15
·8468
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IF 6.208
Innocent U. Okagu,Timothy P. C. Ezeorba,Rita N. Aguchem,Ikenna C. Ohanenye,Emmanuel C. Aham,Sunday N. Okafor,Carlotta Bollati,Carmen Lammi
The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs’ adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conductedex vivoand mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.Keywords:bioactive compounds;bone diseases;bone remodeling;natural products;osteoprotective properties;bone signaling pathways
研究领域:
医学
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生物学
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DOI
PubMed
高影响因子
ADVANCED POWDER TECHNOLOGY
·
2019
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IF 3.25
Xu Liu,Haishan Shi,Tao Yu,Changren Zhou
Nowadays, the treatment of osteoarthritis (OA), a highly prevalent joint disorder, remains a medical challenge because of the lack of understanding of its pathogenesis. In this work, we developed an alternative strategy of OA treatment using magnesium-based materials as potential therapeutic agent towards subchondral bone remodeling. We selected deer antlers as the animal model where calcification behaviors could provide interesting references for the rapid and reproducible endochondral bone growth. Extremely high content of Mg was detected in the antler, which was able to affect the evolutions of biological apatite. Herein, octacalcium phosphate (OCP) and amorphous calcium phosphate (ACP), which are critically involved in the calcification process, were respectively synthesized under the Mg-containing conditions to understand the role of Mg in the evolution of biological apatite. Results showed that the substitution of Mg 2+ at lower contents stabilized OCP and ACP, while higher contents of Mg inhibited the formation of both phases. The size of both calcium phosphates was also altered significantly by the addition of Mg. The results of cell culture indicated that excess Mg notably accelerated the secretion of extracellular matrix and inhibited the mineralization of chondrocyte matrix. Hence, utilization of Mg-based materials in subchondral bone was supposed to provide a potential therapeutic approach to treat the OA by inhibiting subchondral of ossification process.
研究领域:
生物材料
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骨科
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生物矿化
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2018
·Vol. 7
·期 3
·1101-1116
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IF 5.831
Ting-ben Huang,Yong-zheng Li,Ke Yu,Zhou Yu,Ying Wang,Zhi-wei Jiang,Hui-ming Wang,Guo-li Yang
Bone remolding involves the formation of new bone by osteoblasts and the absorption of old bones by osteoclasts. Due to the vital role of osteoblasts and osteoclasts during bone regeneration, it might be feasible to promote osseointegration around the titanium implants by stimulating osteoblasts and inhibiting osteoclasts by modifying the surfaces of the implants. Lithium is used in the treatment of psychiatric patients, and it may be associated with osteogenesis. In this study, lithium was incorporated with sandblasted, large-grit and acid-etched titanium implants via a hydrothermal treatment. In vitro, the nano-scale surface enhanced the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). Moreover, the SLA-Li surface displayed a negative effect on the process of osteoclastogenesis. Further mechanism analysis indicated that the canonical Wnt/β-catenin signaling pathway was activated according to the results of RT-PCR and western blotting. More importantly, the RANKL/OPG signaling axis was also involved in these effects on the SLA-Li surface. The experiments in vivo proved that the SLA-Li surface could induce the bone formation and osseointegration during the early osseointegration after the dental implant surgery. These results suggested that bone homeostasis could be manipulated by an SLA-Li surface, which implied that this new surface might serve as a promising material for clinical application in the future.
研究领域:
生物材料
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组织工程
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骨科
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牙科种植学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Yingtao Gao,Yanyun Pang,Shuo Wei,Qian Han,Shuting Miao,Min Li,Juanhua Tian,Chengyu Fu,Zhengge Wang,Xu Zhang,Peng Yang,Yongchun Liu
Polyetheretherketone (PEEK), a widely used implant material, has attracted the attention of scientific researchers because of its bone-matched elastic modulus, radiolucency, and chemical resistance. However, the bioinert chemical properties of PEEK do not promote bone apposition once implanted. In this study, using a phase-transitioned lysozyme (PTL) nanofilm as a sandwiched layer, a robust hydroxyapatite (HAp) coating on PEEK (HAp@PTL@PEEK) is constructed. The PTL nanofilm shows strong adhesion to the PEEK surface and induces biomimetic mineralization to form a compact HAp coating on PEEK in simulated body fluids. This HAp coating not only shares a higher adhesion strength and better stability but can also be applied to implants with complex 3D structures. HAp@PTL@PEEK showed significantly enhanced osteogenic capacity when cultured with rat bone marrow mesenchymal stem cells by promoting initial cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo evaluations utilizing models of femoral condyle defects and skull defects confirm that the HAp coating substantially augments bone remodeling and osseointegration ability. Compared with the traditional method, our modified method is simpler, more environmentally friendly, and uses less hazardous components. Furthermore, the obtained HAp coating shares a higher adhesion strength to PEEK and a better osteogenic capacity. The study offers a novel method to improve the osseointegration of PEEK-based implants in biointerfaces and tissue engineering.
研究领域:
生物材料
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组织工程
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生物医学工程
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骨科研究
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产品关联
DOI
PubMed
高影响因子
Communications Biology
·
2023
·Vol. 6
·期 1
·1-13
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IF 5.9
Sun Weijia,Li Yuheng,Li Jianwei,Tan Yingjun,Yuan Xinxin,Meng Haoye,Ye Jianting,Zhong Guohui,Jin XiaoYan,Liu Zizhong,Du Ruikai,Xing Wenjuan,Zhao Dingsheng,Song Jinping,Li Youyou,Pan Junjie,Zhao Yunzhang,Li Qi,Wang Aiyuan,Ling Shukuan,Dai Rongji,Li Yingxian
Mechanical force loading is essential for maintaining bone homeostasis, and unloading exposure can lead to bone loss. Osteoclasts are the only bone resorbing cells and play a crucial role in bone remodeling. The molecular mechanisms underlying mechanical stimulation-induced changes in osteoclast function remain to be fully elucidated. Our previous research found Ca 2+ -activated Cl − channel Anoctamin 1 (Ano1) was an essential regulator for osteoclast function. Here, we report that Ano1 mediates osteoclast responses to mechanical stimulation. In vitro, osteoclast activities are obviously affected by mechanical stress, which is accompanied by the changes of Ano1 levels, intracellular Cl − concentration and Ca 2+ downstream signaling. Ano1 knockout or calcium binding mutants blunts the response of osteoclast to mechanical stimulation. In vivo, Ano1 knockout in osteoclast blunts loading induced osteoclast inhibition and unloading induced bone loss and. These results demonstrate that Ano1 plays an important role in mechanical stimulation induced osteoclast activity changes.
研究领域:
生物学
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生物力学
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细胞生物学
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骨生理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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IF 7.7
Fuchao Chu,Zhenxin Wang,Dazhen Zhang,Wenkang Xu,Boyan Huang,Chen Long,Shuo Yang,Xinzhe Qu,Cunjiu Gao,Feng Yuan
Although titanium alloy is the most widely used endoplant material in orthopedics, the material is bioinert and good bone integration is difficult to achieve. Zoledronic acid (ZOL) has been shown to locally inhibit osteoclast formation and prevent osteoporosis, but excessive concentrations of ZOL exert an inhibitory effect on osteoblasts; therefore, stable and controlled local release of ZOL may reshape bone balance and promote bone regeneration. To promote the adhesion of osteoblasts to many polar groups, researchers have applied gelatine methacryloyl (Gelma) combined with polyacrylamide hydrogel (PAAM), which significantly increased the hydrogen bonding force between the samples and improved the stability of the coating and drug release. A series of experiments demonstrated that the Gelma/PAAM-ZOL bioactive coating on the surface of the titanium alloy was successfully prepared. The coating can induce osteoclast apoptosis, promote osteoblast proliferation and differentiation, achieve dual regulation of bone regeneration, successfully disrupt the balance of bone remodelling and promote bone tissue regeneration. Additionally, the coating improves the metal biological inertness on the surface of titanium alloys and improves the bone integration of the scaffold, offering a new strategy for bone tissue engineering to promote bone technology.
研究领域:
骨科
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组织工程
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生物材料
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2021
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IF 7.376
Xiaorong Zhang,Yun Jiang,Jiajie Mao,Xuekun Ren,Yinghui Ji,Yixin Mao,Yang Chen,Xiaoyu Sun,Yihuai Pan,Jianfeng Ma,Shengbin Huang
Reactive oxygen species (ROS) overproduction promotes the alveolar bone loss during the development of periodontitis . Mitochondria are the principal source of ROS. Hydroxytyrosol (HT), a natural phenolic compound present in olive oil, is well known for its antioxidant and mitochondrial-protective prosperities. Nonetheless, the impact of HT on periodontitis and its related mechanisms underlying bone cell behavior remains unknown. Osteoclasts differentiated from RAW264.7 model and oxidative stress (OS) induced pre-osteoblast MC3T3-E1 cell injury model were treated with and without HT. Cell viability , apoptosis , differentiation, mitochondrial function along with mitogen-activated protein kinase (MAPK) signaling pathway were investigated. Meanwhile, the effect and related mechanisms of HT on bone loss in mice with periodontitis were also detected. HT inhibited osteoclast differentiation and prevented OS induced pre-osteoblast cells injury via regulating mitochondrial function as well as ERK and JNK signaling pathways. Moreover, HT attenuated the alveolar bone loss, increased bone forming activity, inhibited the osteoclasts differentiation and decreased the level of OS in mice with periodontitis. Our findings, for the first time , revealed a novel function of HT in bone remodeling of periodontitis, and highlighted its therapeutical potential for the prevention/treatment of periodontitis.
研究领域:
牙科
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2021
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IF 7.328
Mingyue Wang,Chenxi Wang,Yu Zhang,Ye Lin
Bone diseases, for example, osteoporosis, cause excessive differentiation of osteoclasts and decreased bone formation, resulting in imbalance of bone remodeling and poor osseointegration, which can be considered a relative contraindication for titanium implants. Dopamine (DA) might provide a solution to this problem by inhibiting osteoclasts and promoting osteoblasts at different concentrations. However, current commercial implants cannot load bone-active molecules, such as DA. Therefore, this study aimed to develop a surface modification method for implants to achieve a controlled release of DA and enhance the resistance of titanium implants to bone resorption and bone regeneration. DA-loaded alginate-arginine-glycine-aspartic acid (RGD) (AlgR) coatings on a vaterite-modified titanium surface were successfully assembled, which continuously and steadily released DA. In vitro studies have shown that materials showing good biocompatibility can not only inhibit receptor activator of nuclear factor-kappa B (NFκB) ligand (RANKL)-induced osteoclastogenesis but also enhance the adhesion and osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The optimal DA-loaded concentration of this bidirectional regulation is 100 μM. Interestingly, DA more effectively attenuated osteoclastogenesis when released in a sustained manner from titanium coatings than it did via traditional, free administration, and the alginate-RGD coating and DA clearly exhibited great synergy. This study provides a design of titanium implant surface modification to improve bone remodeling around implants.
研究领域:
生物材料
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组织工程
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骨科
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生物医学工程
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2022
·Vol. 6
·期 2
·2200149
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IF 5.003
Kai Zhang,Junlong Da,Jianqun Wang,Lixue Liu,Xinpeng Liu,Haoze Yuan,Lili Jiang,Yawei Geng,Xiaoyao Liu,Zhuling Jiang,Han Jin,Ying Li,Bin Zhang
Bone damage results from the imbalance of bone homeostasis maintained by osteoblast-regulated bone formation and osteoclast-mediated bone resorption. Conventional drug therapy and gene therapy may not optimally regulate the bone remodeling process due to the unitary pharmacological mechanism of drug and the safety and targeting of gene vectors. In the present study, multifunctional fluorescent alendronate-polyethyleneimine carbon dots (Alen-PEI CDs) are innovatively synthesized, which have excellent biocompatibility, selective bone targeting, gene carrying capacity, and anti-bone absorption effect. As gene vectors, bone morphogenic protein 2 (BMP2) gene-loaded Alen-PEI CDs greatly enhance osteoblast differentiation and bone regeneration. Notably, Alen-PEI CDs are found to directly inhibit the formation and function of osteoclasts, effectively attenuating the LPS-induced skull osteolysis in mice. Furthermore, their cumulative toxicity is lower than that of Alen, indicating their potential as an anti-bone resorptive nanodrug. These results show that the bone-targeting Alen-PEI CDs significantly reverse the imbalance of bone homeostasis through a dual-directional mechanism—directly suppressing bone resorption and indirectly inducing bone formation by transfection of osteogenic therapeutic genes. Overall, the study expands the application for carbon dots in biomedicine, providing new insights for the further development of novel selectively targeted multifunctional nanodrugs for the treatment of bone-destructive diseases.
研究领域:
生物医学工程
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药学
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分子生物学
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组织工程
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Xiaomeng Li,Shuaibing Liu,Shanshan Han,Qingqing Sun,Jianmin Yang,Yuhang Zhang,Yongchao Jiang,Xiaofeng Wang,Qian Li,Jianglin Wang
Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through three-dimensional (3D) and spatiotemporal changes in vivo. The matrix stiffness as a crucial factor during bone tissue development is dynamic stiffening. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, we create a dynamic and controllable stiffening 3D biomimetic model to regulate the osteoblastic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. Our findings showed that these dynamic hydrogels allowed cells to spread and volume expansion prior to secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, presented the significantly elevated osteogenic ECM secretion, gene expression, and YAP/TAZ nuclear localization. In vivo evaluation of animal experiments further indicated that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promoted bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo. This article is protected by copyright. All rights reserved
研究领域:
生物材料
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组织工程
·
再生医学
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细胞生物学
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生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
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IF 6.6
Min Chen,Tao Liu,Wenqiang Li,Yingting Li,Puxin Zhong,Huanchen Yan,Jingyin Kong,Weixiang Liang
Background Cartilage-related diseases, such as hypoplastic chondrodysplasia a rare genetic disorder that affects newborns, causing abnormal cartilage development and restricted skeletal growth. However, the development of effective treatment strategies for chondrodysplasia still faces significant challenges due to limitations in the controlled drug delivery, biocompatibility, and biodegradability of nanomedicines.Methods A biodegradable magnesium doped-silicon based-nanoplatforms based on silicon nanoparticles (MON) was constructed. Briefly, the MON was modified with sulfhydryl groups using MPTMS to form MOS. Further engineering of MOS was achieved by incorporating Mg2+ ions through the “dissolution-regrowth” method, resulting in MMOS. Ica was effectively loaded into the MMOS channels, and HA was anchored on the surface of MOS to obtain MMOS-Ica@HA nanoplatforms. Additionally, in vitro cell experiments and in vivo zebrafish embryo models were used to evaluate the effect of the nanoplatforms on cartilage differentiation or formation and the efficiency of treating chondrodysplasia.Results A series of characterization tests including TEM, SEM, DLS, XPS, EDX, and BET analysis validate the successful preparation of MOS-Ica@HA nanoplatforms. The prepared nanoplatforms show excellent dispersion and controllable drug release behavior. The cytotoxicity evaluation reveals the good biocompatibility of MOS-Ica@HA due to the sustained and controllable release of Ica. Importantly, the presence of Ica and Mg component in MOS-Ica@HA significantly promote chondrogenic differentiation of BMSCs via the Smad5/HIF-1α signaling pathway. In vitro and in vivo experiments confirmed that the nanoplatforms improved chondrodysplasia by promoting cartilage differentiation and formation.Conclusion The findings suggest the potential application of the developed biodegradable MMOS-Ica@HA nanoplatforms with acceptable drug loading capacity and controlled drug release in chondrodysplasia treatment, which indicates a promising approach for the treatment of chondrodysplasia.
研究领域:
生物医学工程
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纳米技术
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组织工程
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再生医学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）