Advanced Healthcare Materials
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2025
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IF 9.6
Junlin Chen,Qingtao Li,Chuhan Lv,Hongbo Yu,Cheng Dai,Ye Hu,Hua Dong
Articular cartilage repair remains challenging due to the inherent poor self-healing capacity and acute inflammation resulting from the over expression of intracellular reactive oxygen species (ROS). Although microfracture is frequently used in practical surgery, the newborn cartilage always exhibits fibrosis, mainly attributed to the weak ROS scavenging and mismatched microenvironment that fails to induce chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Herein, a novel simvastatin (SIM)-incorporated kelp and cartilage acellular matrix hybrid (labeled as SIM@KACM/CACM) microgel assembly with enhanced ROS scavenging, endogenous BMSC recruitment, and chondrogenic differentiation capabilities is constructed to improve microfracture-based articular cartilage repair. The kelp acellular matrix exhibits low immunogenicity, high biocompatibility, and ROS scavenging properties, whilst the sustained SIM release promotes BMSC recruitment from the bone marrow cavity. Meanwhile, the microenvironment and bioactive factors conferred by CACM facilitate the BMSC proliferation and differentiation into hyaline cartilage. In addition, the construction of porous microgel assembly via dynamic Schiff's bonds endows excellent injectability and tissue adhesion, which not only enhances its retention in the defect site after injection but also provides abundant sites for BMSC anchoring and infiltration. Due to the synergetic effect of the above-mentioned multiple factors, the articular cartilage repair is improved dramatically.
研究领域:
医学
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组织工程
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再生医学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Jianhua Zeng,Shilang Xiong,Jingyu Zhou,Peng Wei,Kai Guo,Feng Wang,Min Ouyang,Zhisheng Long,Aihua Yao,Jingtang Li,Long Xiong,Desheng Wu
Introduction Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing.Methods Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model.Results SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery.Conclusion The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.
研究领域:
组织工程
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生物医用材料
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再生医学
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骨生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yuanming Xiao,Yangyang Qu,Xuankai Hu,Jinmin Zhao,Sheng Xu,Li Zheng,Xiaonan Liang
Effective membranes that have the osteogneic potential and the ability to recruit osteoblast precursor cells challenged guided bone regeneration (GBR). Herein, we engineered multifunctional nanofiber membranes by using eletrospun poly(ε-caprolactone) (PCL) and silk fibroin (SF), incorporated with octacalcium phosphate (OCP) and BMSCs-affine peptide (E7) to form the PCL/SF/OCP/E7 (PSOE) nanofiber, wherein the E7 peptide enhances the enrichment of BMSCs, and OCP as osteogenesis promoter. The composite membranes enhance the recruitment and biomineralization processes essential for bone regeneration. Notably, the dual functionality of BMSC recruitment and osteoinduction provides a “recruitment-osteoinduction” strategy that significantly improves bone repair. In vitro analyses confirmed that the PSOE nanofibers have superior hydrophilicity and biocompatibility, and significantly upregulated the expression of osteogenic genes in mesenchymal stem cells, thereby facilitating osteogenic differentiation. In vivo studies using a rat tibial defect model revealed that PSOE nanofibers promoted bone repair within 8 weeks, as validated by micro-CT and histological evaluations. This study highlights the PSOE nanofiber's potential as a promising synthetic periosteum substitute for effective bone regeneration.
研究领域:
生物材料
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组织工程
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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
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-14
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IF 10.2
Zhao Yitong,Bo Tao,Wang Chenfei,Yao Dingjin,Pan Chaolan,Xu Weiyi,Zhou Hao,Li Ming,Zhang Si
Extensive efforts have been dedicated to enhancing the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in cancer cells for the development of effective cancer treatments. However, highly safe and efficient delivery of TRAIL gene remains a significant challenge, especially using cationic polymers. Here, a series of highly branched-linear poly(β-amino ester)s (H-LPAEs) are developed through a unique oligomer branching strategy. H-LPAEs exhibit a more uniform distribution of linear segments and branching units, leading to excellent DNA condensation and favorable physicochemical properties of H-LPAE/DNA polyplexes. In SW1353 and BMSC cells, the optimized H-LPAEs, H-LPAE B4−S5−TMPTA , achieves superior gene transfection efficiency of 58.0% and 33.4%, which were 2.5-fold and 2.0-fold higher than that of the leading commercial gene transfection reagent, Lipofectamine 3000. Excitingly, H-LPAE B4−S5−TMPTA mediated 56.7% and 28.1% cell apoptosis in HepG2 cells and HeLa cells highlighting its potential application in cancer gene therapy. In addition, locally administered H-LPAE B4−S5−TMPTA delivered TRAIL DNA to HepG2 xenograft tumors and inhibited tumor growth in vivo. This study not only proposes a novel strategy for synthesizing poly(β-amino ester)s with a unique branched-linear topology but also identifies a promising candidate for highly efficient TRAIL gene transfection.
研究领域:
癌症研究
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基因治疗
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聚合物化学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Zhou Mengyang,Guo Min,Shi Xincui,Ma Jie,Wang Shutao,Wu Shuo,Yan Weiqun,Wu Feng,Zhang Peibiao
Multifunctionality has becoming essential for bone tissue engineering materials, such as drug release. In this study, icariin (ICA)-incorporated poly(glycolide-co-caprolactone) (PGCL) porous microcarriers were fabricated and then coated with decellularized extracellular matrix (dECM) which was derived from bone marrow mesenchymal stem cells (BMSC). The porous structure was generated due to the soluble gelatin within the microcarriers. The initial released ICA in microcarriers regulated osteogenic ECM production by BMSCs during ECM formation. The dECM could further synergistically enhance the migration and osteogenic differentiation of BMSCs together with ICA as indicated by the transwell migration assay, ALP and ARS staining, as well as gene and protein expression. Furthermore, in vivo results also showed that dECM and ICA exhibited excellent synergistic effects in repairing rat calvarial defects. These findings suggest that the porous microcarriers loaded with ICA and dECM coatings have great potential in the field of bone tissue engineering.
研究领域:
组织工程
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生物材料
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干细胞生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
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2022
·Vol. 13
·期 1
·1-20
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IF 17.694
Wang Zhen-Xing,Luo Zhong-Wei,Li Fu-Xing-Zi,Cao Jia,Rao Shan-Shan,Liu Yi-Wei,Wang Yi-Yi,Zhu Guo-Qiang,Gong Jiang-Shan,Zou Jing-Tao,Wang Qiang,Tan Yi-Juan,Zhang Yan,Hu Yin,Li You-You,Yin Hao,Wang Xiao-Kai,He Ze-Hui,Ren Lu,Liu Zheng-Zhao,Hu Xiong-Ke,Yuan Ling-Qing,Xu Ran,Chen Chun-Yuan,Xie Hui
Adipocyte differentiation of bone marrow mesenchymal stem/stromal cells (BMSCs) instead of osteoblast formation contributes to age- and menopause-related marrow adiposity and osteoporosis. Vascular calcification often occurs with osteoporosis, a contradictory association called “calcification paradox”. Here we show that extracellular vesicles derived from aged bone matrix (AB-EVs) during bone resorption favor BMSC adipogenesis rather than osteogenesis and augment calcification of vascular smooth muscle cells. Intravenous or intramedullary injection of AB-EVs promotes bone-fat imbalance and exacerbates Vitamin D3 (VD3)-induced vascular calcification in young or old mice. Alendronate (ALE), a bone resorption inhibitor, down-regulates AB-EVs release and attenuates aging- and ovariectomy-induced bone-fat imbalance. In the VD3-treated aged mice, ALE suppresses the ovariectomy-induced aggravation of vascular calcification. MiR-483-5p and miR-2861 are enriched in AB-EVs and essential for the AB-EVs-induced bone-fat imbalance and exacerbation of vascular calcification. Our study uncovers the role of AB-EVs as a messenger for calcification paradox by transferring miR-483-5p and miR-2861.
研究领域:
骨骼生物学
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干细胞生物学
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血管生物学
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老年学
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分子生物学
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DOI
PubMed
高影响因子
Science Advances
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2024
·Vol. 10
·期 42
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IF 11.7
Xulong Liu,Shangtong Jiang,Ting Jiang,Ziyang Lan,Xin Zhang,Zhenyu Zhong,Xiaodan Wu,Cunjing Xu,Yingying Du,Shengmin Zhang
Cartilage regeneration relies on adequate and continuous bioenergy supply to facilitate cellular differentiation and extracellular matrix synthesis. Chondrocytes frequently undergo energy stress under pathological conditions, characterized by disrupted cellular metabolism and reduced adenosine triphosphate (ATP) levels. However, there has limited progress in modulating energy metabolism for cartilage regeneration thus far. Here, we developed bioenergetic-active exosomes (Suc-EXO) to promote cartilage regeneration and homeostasis maintenance. Suc-EXO exhibited a 5.42-fold increase in ATP content, enabling the manipulation of cellular energy metabolism by fueling the TCA cycle. With continuous energy supply, Suc-EXO promoted BMSC chondrogenic differentiation via the P2X7-mediated PI3K-AKT pathway. Moreover, Suc-EXO improved chondrocyte anabolism and mitochondrial homeostasis via the P2X7-mediated SIRT3 pathway. In a rabbit cartilage defect model, the Suc-EXO–encapsulated hydrogel notably promoted cartilage regeneration and maintained neocartilage homeostasis, leading to 2.26 and 1.53 times increase in Col2 and ACAN abundance, respectively. These findings make a remarkable breakthrough in modulating energy metabolism for cartilage regeneration, offering immense potential for clinical translation.
研究领域:
再生医学
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细胞代谢
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组织工程
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生物医学工程
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DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2023
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IF 3.8
Bing Liang,Xiongbin Chen,Min Li,Lingling Zhang,Xia Yang,Liangqin Shi,Yanju Gong,Yuanyuan Gong,Huan Xu,Xiao Wu,Zhong Jin,Yanru Wang,Luwei Liu,Xiaohong Yi,Lushuang Xie,Hua Zhong,Chongyang Shen,Yong Wang,Lan Yang
Context Liuwei Dihuang pill (LWDH) has been used to treat postmenopausal osteoporosis (PMOP).Objective To explore the effects and mechanisms of action of LWDH in PMOP.Materials and methods Forty-eight female Sprague-Dawley rats were divided into four groups: sham-operated (SHAM), ovariectomized (OVX), LWDH high dose (LWDH-H, 1.6 g/kg/d) and LWDH low dose (LWDH-L, 0.8 g/kg/d); the doses were administered after ovariectomy via gavage for eight weeks. After eight weeks, the bone microarchitecture was evaluated. The effect of LWDH on the differentiation of bone marrow mesenchymal stem cells (BMSCs) was assessed via osteogenesis- and lipogenesis-induced BMSC differentiation. The senescence-related biological indices were also detected using senescence staining, cell cycle analysis, quantitative real-time polymerase chain reaction and western blotting. Finally, the expression levels of autophagy-related proteins and Yes-associated protein (YAP) were evaluated.Results LWDH-L and LWDH-H significantly modified OVX-induced bone loss. LWDH promoted osteogenesis and inhibited adipogenesis in OVX-BMSCs. Additionally, LWDH decreased the positive ratio of senescence OVX-BMSCs and improved cell viability, cell cycle, and the mRNA and protein levels of p53 and p21. LWDH upregulated the expression of autophagy-related proteins, LC3, Beclin1 and YAP, in OVX-BMSCs and downregulated the expression of p62.Discussion and conclusions LWDH improves osteoporosis by delaying the BMSC senescence through the YAP-autophagy axis.
研究领域:
药理学
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骨科
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干细胞生物学
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老年医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Yutong Chen,Mengru Zhu,Shihao Sheng,Huijian Yang,Qin Zhang,Xiao Chen,Ke Xu,Mengmeng Li,Biaotong Huang,Qinglin Han,Yingying Jiang,Jiacan Su
Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mineral density and a heightened risk of fractures. Therapies for OP have primarily focused on balancing bone formation and bone resorption, but enhancing the remineralization of osteoporotic bone is also a key strategy for effective repair. Recent insights into biomineralization mechanisms have highlighted the essential role of mineral-containing extracellular vesicles (EVs) secreted by osteoblasts in promoting bone marrow mesenchymal stromal/stem cell (BMSC) differentiation and initiating matrix mineralization. Drawing from these principles, we developed a biomimetic approach to replicate the structure and function of the osteoblast-derived EVs by engineering biomimetic mitochondrial minerals with bone marrow homing cell membranes (CMs). This bone-targeted biomimetic system exhibits excellent biocompatibility, enhancing osteogenic differentiation and stimulating angiogenesis by regulating cellular energy metabolism. Additionally, the CM-coated structure shows affinity for collagen fibrils, effectively enhancing intrafibrillar collagen mineralization, thereby facilitating osteoporotic bone repair. Overall, the biomimetic system offers a safe and efficient therapeutic alternative, positioning it as a platform for bone tissue engineering and regenerative medicine.
研究领域:
生物医学工程
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组织工程
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再生医学
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骨科
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
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IF 2.5
Shuangliu Chen,Yalan Pan,Yang Guo,Xiaoxian Sun,Xue Bai,Mengmin Liu,Lining Wang,Jiřimutu Xiao,Cheng Chen,Yong Ma
This study utilized bioinformatics and data mining techniques to explore the molecular mechanism of curcumin in treating osteoporosis (OP) through the lens of ferroptosis, thereby identifying novel therapeutic targets. The datasets GSE35958, GSE35956, GSE7429, and GSE7158 were obtained from the Gene Expression Omnibus (GEO) database. GSE35958 and GSE35956 were employed as training sets for data integration, while GSE7429 and GSE7158 served as independent validation sets. Through retrieval from the FerrDb database, iron death-related genes (FRGs) were identified, and the differentially expressed genes (DEGs) were intersected to obtain differentially expressed FRGs (DEFRGs). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, followed by the construction of a Protein-Protein Interaction (PPI) network to identify Hub genes. The DGIdb database was utilized to predict candidate drugs associated with the Hub genes, and molecular docking and in vitro experiments confirmed that curcumin targets the Hub genes EGFR and PTGS2.Through in vitro testing of curcumin on BMSC cells, researchers examined cell vitality, iron death, osteogenic differentiation, mineralization, and the impact on EGFR and PTGS2 levels. The analysis yielded 2212 DEGs, 484 FRGs, with 45 FDEGs at the intersection. GO analysis revealed involvement in regulating mitochondrial proteins, amino acid transport across plasma membranes, and protein ubiquitination. KEGG pathway analysis indicated associations with iron death, FoxO signaling, mTOR signaling, cell aging, osteoclast differentiation, and GSH metabolism. Utilizing the MCC algorithm, five Hub genes were identified: MAPK3, PTGS2, TGFB1, CYBB, and EGFR, showing diagnostic potential for iron death. Curcumin displayed affinity for EGFR and PTGS2, mitigating iron-induced effects on BMSCs such as increased reactive oxygen species, Fe3+ levels, and decreased mitochondrial membrane potential. Furthermore, curcumin reversed these effects, suggesting EGFR and PTGS2 as targets for curcumin to inhibit BMSC ferroptosis and potentially delay osteoporosis development. Maintaining iron homeostasis and targeting BMSC ferroptosis could offer therapeutic avenues for iron overload-induced osteoporosis.
研究领域:
生物信息学
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药理学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
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