INTERNATIONAL JOURNAL OF CANCER
·
2024
·
IF 5.7
Jiaxin Ren,Cheng Zhao,Ruizhu Sun,Jian Sun,Laiya Lu,Jun Wu,Shuaijun Li,Lei Cui
Due to the lack of a precise in vitro model that can mimic the nature microenvironment in osteosarcoma, the understanding of its resistance to chemical drugs remains limited. Here, we report a novel three-dimensional model of osteosarcoma constructed by seeding tumor cells (MG-63 and MNNG/HOS Cl no. 5) within demineralized bone matrix scaffolds. Demineralized bone matrix scaffolds retain the original components of the natural bone matrix (hydroxyapatite and collagen type I), and possess good biocompatibility allowing osteosarcoma cells to proliferate and aggregate into clusters within the pores. Growing within the scaffold conferred elevated resistance to doxorubicin on MG-63 and MNNG/HOS Cl no. 5 cell lines as compared to two-dimensional cultures. Transcriptomic analysis showed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism in osteosarcoma cells in demineralized bone matrix scaffolds. Inhibition of glutamine metabolism resulted in a decrease in drug resistance of osteosarcoma, which could be restored by α-ketoglutarate supplementation. Overall, our study suggests that microenvironmental cues in demineralized bone matrix scaffolds can enhance osteosarcoma drug responses and that targeting glutamine metabolism may be a strategy for treating osteosarcoma drug resistance. What's new? Osteosarcoma resistance to chemical drugs remains poorly understood. Here, the authors constructed a novel three-dimensional osteosarcoma model by seeding tumor cells within demineralized bone matrix scaffolds. Growing within the scaffold conferred elevated doxorubicin resistance to osteosarcoma cells when compared to two-dimensional cultures. Osteosarcoma cells in demineralized bone matrix scaffolds displayed an increased enrichment for drug resistance genes along with enhanced glutamine metabolism. This model could help better understand the complex cell–matrix interactions between osteosarcoma cells and surrounding native bone and potentially screen novel effective chemotherapies to treat osteosarcoma.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-20
·
IF 3.9
Wu Honghan,Huang Jun,Wu Hengpeng,Xu Weikang,Zhong Qian,Song Jiaxiang,Linghu Xitao,Gao Botao,Wa Qingde
Autologous and allogeneic bone grafting is currently the clinical gold standard for the treatment of bone defects; however, it is limited by the scarcity of autologous sources and the risk of secondary trauma, as well as the complications of disease transmission and immune rejection associated with allogeneic grafts. The clinical management of bone defects remains a significant challenge. In this study, we prepared a demineralized bone matrix/gelatin methacrylate composite hydrogel loaded with deferoxamine (GelMA/DBM/DFO) using a freeze-drying method and investigated its properties. Assessments using CCK-8, live-dead fluorescence staining, alkaline phosphatase staining, and Alizarin Red staining indicated that the GelMA/DBM/DFO composite hydrogel demonstrated superior biocompatibility and in vitro osteogenic differentiation capacity compared with the GelMA/DBM composite hydrogel. We established a cranial defect model in Sprague–Dawley (SD) rats and examined peripheral blood indices, micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) staining, Masson’s trichrome staining, and immunohistochemical staining for bone morphogenetic protein-2 (BMP-2) and collagen type I (COL-1). Both hydrogels exhibited good biosafety and the GelMA/DBM/DFO hydrogel showed more effective repair of cranial defects in SD rats. This study provides a novel material for bone-defect repair.
研究领域:
生物医学工程
·
骨组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2014
·Vol. 9
·期 3
·035008
·
IF 2.922
Hongjie Huang,Xin Zhang,Xiaoqing Hu,Linghui Dai,Jingxian Zhu,Zhentao Man,Haifeng Chen,Chunyan Zhou,Yingfang Ao
Hydrogels are attractive for cartilage tissue engineering because of their high plasticity and similarity with the native cartilage matrix. However, one critical drawback of hydrogels for osteochondral repair is their inadequate mechanical strength. To address this limitation, we constructed a solid-supported thermogel comprising a chitosan hydrogel system and demineralized bone matrix. Scanning electron microscopy, the equilibrium scanning ratio, the biodegradation rate, biomechanical tests, biochemical assays, metabolic activity tests, immunostaining and cartilage-specific gene expression analysis were used to evaluate the solid-supported thermogel. Compared with pure hydrogel or demineralized matrix, the hybrid biomaterial showed superior porosity, equilibrium swelling and degradation rate. The hybrid scaffolds exhibited an increased mechanical strength: 75% and 30% higher compared with pure hydrogels and demineralized matrix, respectively. After three days culture, bone-derived mesenchymal stem cells (BMSCs) maintained viability above 90% in all three materials; however, the cell retention of the hybrid scaffolds was more efficient and uniform than the other materials. Matrix production and chondrogenic differentiation of BMSCs in the hybrid scaffolds were superior to its precursors, based on glycosaminoglycan quantification and hyaline cartilage marker expression after three weeks in culture. Its easy preparation, favourable biophysical properties and chondrogenic capacity indicated that this solid-supported thermogel could be an attractive biomaterial framework for cartilage tissue engineering.
研究领域:
生物材料学
·
再生医学
·
组织工程学
✓ 已验证
DOI
PubMed
高影响因子
CELL AND TISSUE BANKING
·
2021
·Vol. 22
·期 3
·443-451
·
IF 1.522
Kang Bo Kyoung,Yu Zheyuan,Chen Weiming,Jiang Taoran,Shim Yoong-hun,Gao Jiaman,Zhou Guangdong,Cao Dejun
Engineered cartilage has several applications in treating cartilage ossification, however, its use is restricted clinically. We explored the feasibility of engineered cartilage in constructing tissues using gelatin/curcumin nano-fiber membranes as scaffolds in subcutaneous models. We constructed cartilage with gelatin nano-fiber membrane (control group) and gelatin/curcumin nano-fiber membrane (experimental group) as scaffolds. After the material was implanted into the back of BALB/c mice, gross view observation was performed. Histological examination was performed 3 and 12 weeks after implantation in vivo, and cartilage formation at different time points was compared. Gross observation showed that compared to the control group, the vascularization of nearby tissues in the experimental group was significantly inhibited. The Scanning electron microscope observation showed that the chondrocytes in both groups adhered well. The growth curve of the chondrocytes showed that curcumin had no significant effect on cell growth. Histological observation showed that the cell-material complexes in both groups had cartilage lacuna formation at 3 and 12 weeks. However, compared with that of the control group, the experimental group showed obvious absorption and thicker cartilage matrix with more homogenization. Gelatin/curcumin scaffolds were successfully used to construct engineered cartilage tissues in subcutaneous animal models. Our findings demonstrate that curcumin-loaded scaffolds have great clinical applications.
研究领域:
生物医学工程
·
组织工程学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2022
·
IF 6.113
Zhongrun Yuan,Sa Liu,Wenjing Song,Ying Liu,Gangyuan Bi,Renjian Xie,Li Ren
Galactose, an important carbohydrate nutrient, is involved in several types of cellular metabolism, participating in physiological activities such as glycosaminoglycan (GAG) synthesis, glycosylation, and intercellular recognition. The regulatory effects of galactose on osteoarthritis have attracted increased attention. In this study, in vitro cell models of ATDC5 and chondrocytes were prepared and cultured with different concentrations of galactose to evaluate its capacity on chondrogenesis and cartilage matrix formation. The cell proliferation assay demonstrated that galactose was nontoxic to both ATDC5 cells and chondrocytes. RT-PCR and immunofluorescence staining indicated that the gene expressions of cartilage matrix type II collagen and aggrecan were significantly upregulated with increasing galactose concentration and the expression and accumulation of the extracellular matrix (ECM) protein. Overall, these results indicated that a galactose concentration below 8 mM exhibited the best effect on promoting chondrogenesis, which entitles galactose as having considerable potential for cartilage repair and regeneration.
研究领域:
细胞生物学
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 30
·6378-6389
·
IF 5.344
Zhuo Liang,Yue Luo,Yonggang Lv
A demineralized bone matrix (DBM) scaffold has good biocompatibility, low antigenicity, a natural porous structure and no cytotoxicity, and so it is an appropriate material for bone regeneration. However, osteoinductive growth factors are often removed during preparation, which destroys the osteoinductive capacity of the DBM scaffold. Biomaterials combined with gene therapy is a promising approach to effectively avoid this adverse side effect. This study develops a human bone morphogenetic protein 2 (hBMP2) gene-activated DBM scaffold to enhance the osteoinductive capacity of DBM and improve bone repair. Bone marrow mesenchymal stem cell (MSC)-derived microvesicles (MVs) were obtained, and polyethyleneimine (PEI) and human bone morphogenetic protein 2 (hBMP2) plasmids (phBMP2) were sequentially coated on the MVs by layer-by-layer (LBL) self-assembly to form an MVs–PEI/phBMP2 non-viral gene vector. Finally, the gene-activated scaffold (DBM/MVs–PEI/phBMP2) was prepared by loading MVs–PEI/phBMP2 onto a DBM scaffold. The experimental results show that the MVs–PEI/phBMP2 exhibits higher transfection efficiency and lower cytotoxicity to MSCs when the MVs/PEI weight ratio = 5, and could enhance the osteogenic differentiation of MSCs in vitro. Subcutaneous implantation into rats showed that the DBM/MVs–PEI/phBMP2 scaffold could efficiently enhance the deposition of: collagen fibers, osteocalcin, osteopontin and CD34 endogenous proteins. Rabbit femoral condyle defect experiments proved that the DBM/MVs–PEI/phBMP2 scaffold could significantly promote bone repair. This study presents a novel, highly efficient and low cytotoxicity gene delivery vector based on MVs. The gene-activated DBM scaffold based on MVs not only could promote bone formation but also angiogenesis, implying that this kind of gene-activated scaffold is a promising bone substitute material.
研究领域:
组织工程
·
再生医学
·
基因治疗
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Zhicheng Tong,Yuanzhu Ma,Qiushi Liang,Tao Lei,Hongwei Wu,Xianzhu Zhang,Yishan Chen,Xihao Pan,Xiaozhao Wang,Huimin Li,Junxin Lin,Wei Wei,Chong Teng
Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Statement of Significance : Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.
研究领域:
组织工程
·
生物材料
·
骨科
·
生物医学工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2022
·
IF 4.85
Yutong Wu,Hongbo Ai,Yuchi Zou,Qiankun Yang,Ce Dou,Jianzhong Xu
Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling , osteoclasts generate large amounts of sEVs. However, there is very few research studying whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p as highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro . Next, we prepared an sEV-modified demineralized bone matrix (DBM) as scaffold treating calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo results indicated that DBM modified with miR-106a-5p-sEVs showed an enhanced capacity for bone regeneration . This important finding further emphasizes that sEV-mediated miR-106a-5p transfer plays a critical role in osteogenesis and indicates a novel communication mode between osteoclasts and BMSCs.
研究领域:
骨骼生物学
·
干细胞研究
·
再生医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Han Yu,Huanhuan Luo,Jianping Chen,Xiaodong Hu,Yujiong Chen,Jiaqi Zhong,Botao Liu,Yanfang Liu,Gang Chen,Chenglong Huang,Zhaoxiang Peng
The utilization of stem cell biotechnology for osteoarthritis (OA) treatment is hindered by high operational costs, difficulties in maintaining stem cell viability, and limited efficacy of unguided stem cell differentiation. Magnesium ions (Mg 2+ ), crucial for tissue regeneration and repair, hold significant potential in OA treatment. However, further investigation is required to elucidate the precise mechanisms of Mg 2+ in OA treatment. Here, we investigated the optimal concentration of Mg 2+ to induce directed differentiation of stem cells and synthesized bioactive hydrogel microspheres (MDGM-Ps) capable of precisely releasing this concentration using microfluidic technology. Synthesized via polymerization of dopamine methacrylamide (DMA) and methacrylated gelatin (GelMA), these microspheres could chelate Mg 2+ and incorporate platelet-derived growth factor-BB into the hydrogel matrix for sustained release. In vitro , MDGM-Ps showed excellent biocompatibility and promoted stem cell recruitment. Importantly, Mg 2+ released from MDGM-Ps could guide stem cell differentiation through the PI3K-AKT pathway. Moreover, in vivo experiments suggested that MDGM-Ps could maintain the cartilage matrix and mitigate the progression of OA. In summary, MDGM-Ps not only harnessed the advantages of stem cell therapy, but also expanded the therapeutic applications of metal ions, thereby presenting a promising candidate for OA therapy.
研究领域:
生物技术
·
干细胞疗法
·
组织工程
·
骨科
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2021
·
IF 6.4
Manman Sun,Ke Huang,Xueshi Luo,Hong Li
Purpose Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A three-dimensional (3D) engineered bone matrix was developed as an effective biomimetic model to explore the mechanism relative to bone cancer metastasis. Methods In the study, a 3D engineered bone matrix was developed via cell biomineralization templated by a biomimetic collagen template. The process of bone metastasis relative to breast cancer was investigated by co-culturing breast cancer MDA-MB-231-GFP cells with pre-osteogenic MC3T3-E1 cells on the 3D bone matrix. Results A typical bone matrix was obtained, where mineralized collagen fibers were packed into the bundle to form a 3D engineered bone matrix. As the cancer cells were invading along the way vertical to the alignment of mineralized collagen fiber, the bone matrix gradually became thinner, accompanied with the erosion of Col I and the loss of calcium and phosphorus. As a result, the disassembled structure of mineralized collagen fiber was observed, which may be attributed to osteolytic bone metastasis. Conclusion An engineered 3D bone-like matrix was successfully prepared via cell mineralization, which can act as a model for bone metastasis process. The study revealed mineralized collagen fiber disassembled at nanoscale relative to breast cancer cells.
研究领域:
癌症生物学
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2018
·
IF 4.432
Hongjie Huang,Xiaoqing Hu,Xin Zhang,Xiaoning Duan,Jiying Zhang,Xin Fu,Linghui Dai,Lan Yuan,Chunyan Zhou,Yingfang Ao
Synovium-derived mesenchymal stem cells (SMSCs) are attractive tissue-specific cells for cartilage regeneration because of their easy availability, higher chondrogenic potential, and joint specificity. In the present study, we established a hybrid scaffold to codeliver SMSCs and transforming growth factor beta (TGF-β), which can integrate the scaffolds, the growth factor, and the autogenous cells within rabbit cartilage defects. A chitosan hydrogel and a decellularized bone matrix were used to fabricate the gel–solid duplex phase biomaterials, which were proven to retain more cells, promote tissue integration, and provide mechanical support. In vitro experiments demonstrated that this hybrid scaffold could release TGF-β in a controlled biphasic pattern, which can promote cell proliferation and chondrogenic differentiation of loaded rabbit SMSCs. For in vivo experiments, we filled cartilage defects with the hybrid materials, delivering autogenous SMSCs and TGF-β simultaneously via chitosan’s sol–gel transition. Histological analysis, magnetic resonance imaging, and nanoindentation assessment indicated superior cartilage regeneration using this codelivery system compared with that from routine microfracture or control delivery scaffolds. Beyond cartilage regeneration, the easy preparation, favorable biophysical properties, and controlled release ability make this codelivery system applicable to transport other tissue-specific cells or biofactors for tissue engineering.
研究领域:
生物医学工程
·
再生医学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-20
·
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
·
干细胞生物学
·
血管生物学
·
老年学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）