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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

A TGF-loading hydrogel scaffold capable of promoting chondrogenic differentiation for repairing rabbit nasal septum cartilage defect

Zhang Dan,Su Ying,Sun Peng,Liu Xingzhi,Zhang Lin,Ling Xuwei,Fan Yuhui,Wu Kang,Shi Qin,Liu Jisheng

Hydrogel-based tissue engineering has been widely used to repair cartilage injury. However, whether this approach can be applied to treat nasal septum cartilage defects remains unclear. In this study, three gelatin methacrylate-based scaffolds loaded with transforming growth factor (TGF)-β1 (GelMA-T) were prepared, and their effects on repair of nasal septum cartilage defects were examined. In vitro, the GelMA-T scaffolds showed good biocompatibility and promoted the chondrogenic differentiation of bone mesenchymal stem cells. Among three scaffolds, the 10% GelMA-T scaffold promoted chondrogenic differentiation most effectively, which significantly improved the expression of chondrocyte-related genes, including Col II, Sox9, and ACAN. In vivo, 10% GelMA-T scaffolds and 10% GelMA-T scaffolds loaded with bone mesenchymal stem cells (BMSCs; 10% GelMA-T/BMSCs) were transplanted into a nasal septum cartilage defect site in a rabbit model. At 4, 12, and 24 weeks after surgery, the nasal septum cartilage defects exhibited more complete repair in rabbits treated with the 10% GelMA-T/BMSC scaffold as demonstrated by hematoxylin & eosin, safranine-O, and toluidine blue staining. We showed that GelMA-T/BMSCs can be applied in physiological and structural repair of defects in nasal septum cartilage, providing a potential strategy for repairing cartilage defects in the clinic.

CAS / MDL: 50-00-0 9000-70-8
研究领域: 组织工程 · 再生医学 · 生物医用材料 · 骨科
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MACROMOLECULAR BIOSCIENCE · 2020 ·Vol. 21 ·期 3 ·2000323 · IF 3.416

Gradient Mineralized and Porous Double-Network Hydrogel Effectively Induce the Differentiation of BMSCs into Osteochondral Tissue In Vitro for Potential Application in Cartilage Repair

Zengjie Fan,Zizi Chen,Hui Zhang,Yingying Nie,Shumei Xu

At present, it is a considerable challenge to mimic the complex architecture of osteochondral (OC) tissue. In this study, a porous and gradient mineralized double-network hydrogel is synthesized and used to induce bone marrow mesenchymal stem cells (BMSCs) to differentiate into the desired OC tissue depending only on the material and mechanical properties. Physical and chemical characterizations show that hydroxyapatite nanoparticles grow and fill into the pores of the hydrogel, and their content presents a gradient change in different layers of hydrogel. The synthesized hydrogel has excellent mechanical properties and the compression strength with different mineralization degrees varies from 27 to 380 kPa, which fully meets the needs of increased mechanical strength of articular cartilage from the surface to the deep layer. Besides, the synthesized hydrogel has good biocompatibility that can promote the proliferation and growth of BMSCs. More importantly, the results of histochemistry, immunohistochemistry, and real time polymerase chain reaction show that gradient mineralized hydrogel can induce BMSCs to differentiate into the desired chondrocytes and osteoblasts in different layers of hydrogels, indicating that OC tissues can be successfully constructed through a simple induction differentiation of gradient mineralized hydrogel.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ORAL DISEASES · 2023 · IF 3.8

Osteogenic effect and mechanism of IL-10 in diabetic rat jaw defect mode

Sitong Hu,Yihui Zhu,Shujia Yu,Yanchuan Guo,Yihu Wang,Menghao Lv,Wei Bai,Pan Ma

Objective The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. Methods Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. Results IL-10 induced expression of arginase 1, TGF-β1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. Conclusions IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.

研究领域: 免疫学 · 骨科 · 再生医学 · 口腔科学
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Journal of Bionic Engineering · 2024 · IF 4.9

Bioinspired Hollow Mesoporous Silica Nanoparticles Coating on Titanium Alloy with Hierarchical Structure for Modulating Cellular Functions

Zhang Jiaxin,Liu He,Wang Jincheng,Shang Jing,Xu Mingwei,Zhu Xiujie,Xu Chao,Bai Haotian,Zhao Xin

3D-printed Porous Titanium Alloy Implants (pTi), owing to their biologically inertness and relatively smooth surface morphology, adversely affect the biological functions of surrounding cells. To address the challenges, constructing a bioinspired interface that mimics the hierarchical structure of bone tissue can enhance the cellular functions of cells. In this context, Hollow Mesoporous Silica Nanoparticles (HMSNs), renowned for their unique physicochemical properties and superior biocompatibility, offer a promising direction for this research. In this research, the initially synthesized HMSNs were used to construct a “hollow-mesoporous-macroporous” hierarchical bioinspired coating on the pTi surface through the Layer-by-Layer technique. Simultaneously, diverse morphologies of coatings were established by adjusting the deposition strategy of PDDA/HMSNs on the pTi surface (pTi-HMSN-2, pTi-HMSN-4, pTi-HMSN-6). A range of techniques were employed to investigate the physicochemical properties and regulation of cellular biological functions of the diverse HMSN coating strategies. Notably, the pTi-HMSN-4 and pTi-HMSN-6 groups exhibited the uniform coatings, leading to a substantial enhancement in surface roughness and hydrophilicity. Meantime, the coating constructed strategy of pTi-HMSN-4 possessed commendable stability. Based on the aforementioned findings, both pTi-HMSN-4 and pTi-HMSN-6 facilitated the adhesion, spreading, and pseudopodia extension of BMSCs, which led to a notable upsurge in the expression levels of vinculin protein in BMSCs. Comprehensive analysis indicates that the coating, when PDDA/HMSNs are deposited four times, possesses favorable overall performance. The research will provide a solid theoretical basis for the translation of HMSN bioinspired coatings for orthopedic implants.

CAS / MDL: 26062-79-3
研究领域: 材料科学 · 生物材料 · 纳米技术 · 组织工程 · 骨科
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CELLULAR SIGNALLING · 2022 · IF 4.85

Osteoclast-derived extracellular miR-106a-5p promotes osteogenic differentiation and facilitates bone defect healing

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
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Tissue Engineering and Regenerative Medicine · 2023 · IF 3.6

MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head

Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo . Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

CAS / MDL: 50-02-2 50-81-7
研究领域: 纳米技术 · 骨科 · 再生医学 · 分子生物学
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Cell Death & Disease · 2024 ·Vol. 15 ·期 3 ·1-16 · IF 8.1

METTL3-dependent m6A modification of PSEN1 mRNA regulates craniofacial development through the Wnt/β-catenin signaling pathway

Ma Lan,Zhou Xi,Yao Siyue,Zhang Xinyu,Mao Ji,Vona Barbara,Fan Liwen,Lou Shu,Li Dandan,Wang Lin,Pan Yongchu

Craniofacial malformations, often associated with syndromes, are prevalent birth defects. Emerging evidence underscores the importance of m 6 A modifications in various bioprocesses such as stem cell differentiation, tissue development, and tumorigenesis. Here, in vivo, experiments with zebrafish models revealed that mettl3 -knockdown embryos at 144 h postfertilization exhibited aberrant craniofacial features, including altered mouth opening, jaw dimensions, ethmoid plate, tooth formation and hypoactive behavior. Similarly, low METTL3 expression inhibited the proliferation and migration of BMSCs, HEPM cells, and DPSCs. Loss of METTL3 led to reduced mRNA m 6 A methylation and PSEN1 expression, impacting craniofacial phenotypes. Co-injection of mettl3 or psen1 mRNA rescued the level of Sox10 fusion protein, promoted voluntary movement, and mitigated abnormal craniofacial phenotypes induced by mettl3 knockdown in zebrafish. Mechanistically, YTHDF1 enhanced the mRNA stability of m 6 A-modified PSEN1 , while decreased METTL3-mediated m 6 A methylation hindered β-catenin binding to PSEN1, suppressing Wnt/β-catenin signaling. Pharmacological activation of the Wnt/β-catenin pathway partially alleviated the phenotypes of mettl3 morphant and reversed the decreases in cell proliferation and migration induced by METTL3 silencing. This study elucidates the pivotal role of METTL3 in craniofacial development via the METTL3/YTHDF1/PSEN1/β-catenin signaling axis.

CAS / MDL: 61-73-4
研究领域: 发育生物学 · 分子生物学 · 遗传学 · 细胞生物学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2019 · IF 4.213

Construction of a biomimetic chemokine reservoir stimulates rapid in situ wound repair and regeneration

Xue-Han Xu,Tie-Jun Yuan,Pei-Wu Ye,Mao-Ze Wang,Hui-Jian Ma,Zhi-Hong Jiang,Yong-Pin Zhang,Li-Hua Peng

Skin is the first protection of human body. It is always challenged by a range of external factors, resulting in the wounds of skin. Hydrogel, as a dressing with multiple advantages, causes increasing interests or the applications in wound treatment. However, the function and importance of micro-environment of wound region are frequently neglected. In this study, we successfully developed a chemokine loaded biomimetic hydrogel as a functional reservoir to stimulate the rapid in situ recruitment of BMSCs for fast wound repair and regeneration. The biomimetic hydrogel was fabricated by using the Polyvinyl alcohol (PVA) combined with chitosan (CS) as the hybrid materials. The fabricated hydrogel possesses many features such as the porous structure, high swelling rate and moisture retention property. More importantly, the incorporated chemokine could be released with a sustained manner from the hydrogel and recruited the bone marrow mesenchymal stem cells (BMSCs) significantly both in vitro & in vivo . Moreover, the hydrogel was demonstrated to be highly biocompatible to the skin tissue without any side effect or irritation observed. Topical delivery of chemokine by the biomimetic PVA/CS hybrid material based hydrogel is demonstrated as a promising carrier to accelerate wound repair and regeneration without inducing scar formation and any other negative complications. The PVA/CS/SDF-1 hydrogel was shown a novel therapeutic system for wound therapy.

CAS / MDL: 9002-89-5
研究领域: 生物医学工程 · 组织工程 · 伤口愈合 · 生物材料
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RSC Advances · 2018 ·Vol. 8 ·期 30 ·16762-16772 · IF 2.936

Modifying collagen with alendronate sodium for bone regeneration applications

Yingcong He,Ting Zhu,Lei Liu,Xuetao Shi,Zhengmei Lin

Phosphorylated materials are attractive candidates for bone regeneration because they may facilitate the construction of a phosphorylated bone extracellular matrix (ECM) to build a beneficial environment for bone formation. Here, we designed and synthesized a new phosphorylated material, collagen type I phosphorylated with alendronate sodium (Col-Aln), based on the biodegradable osteoconductive collagen backbone. Col-Aln can distinctly accelerate in vitro mineralization in simulated body fluid. Col-Aln showed good biocompatibility with bone marrow mesenchymal stem cells (BMSCs) and promoted their adhesion as well as the osteogenic differentiation of BMSCs more effectively than did pure collagen. Furthermore, collagen and Col-Aln scaffolds implanted into a critical-sized rat cranial defect for 4 and 8 weeks were shown to degrade in vivo and helped to facilitate bone growth in the defect, while the phosphate-containing Col-Aln scaffold significantly promoted new bone formation. Col-Aln provides a new strategy to integrate bioactive phosphate molecules via covalent grafting onto biopolymers and has promise for bone regeneration applications.

CAS / MDL: 121268-17-5
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 骨再生
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Materials Today Bio · 2022 · IF 10.761

Construction of artificial periosteum with methacrylamide gelatin hydrogel-wharton's jelly based on stem cell recruitment and its application in bone tissue engineering

Wentao Zhang,Tianze Sun,Jing Zhang,Xiantong Hu,Ming Yang,Liwei Han,Gang Xu,Yantao Zhao,Zhonghai Li

The presence of periosteum can greatly affect the repair of a bone fracture. An artificial periosteum imitates the biological function of natural periosteum, which is capable of protecting and maintaining bone tissue structure and promoting bone repair. In our artificial periosteum, biocompatible methacrylate gelatin was used to provide the mechanical support of the membrane, E7 peptide added bioactivity, and Wharton's jelly provided the biological activity support of the membrane, resulting in a hydrogel membrane (G-E-W) for the chemotactic recruitment of bone marrow mesenchymal stem cells (BMSCs) and promoting cell proliferation and osteogenic differentiation. In an in vitro experiment, the G-E-W membrane recruited BMSCs and promoted cell proliferation and osteogenic differentiation. After 4 weeks and 8 weeks of implantation in a rat skull defect, the group implanted with a G-E-W membrane was superior to the blank control group and single-component membrane group in both quantity and quality of new bone. The artificial G-E-W membrane recruits BMSC chemotaxis and promotes cell proliferation and osteogenic differentiation, thereby effectively improving the repair efficiency of fractures and bone defects.

CAS / MDL: 64-19-7 760-93-0
研究领域: 组织工程 · 生物材料 · 干细胞生物学 · 再生医学 · 骨科
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Journal of Materials Research and Technology-JMR&T · 2024 · IF 6.2

Magnetic scaffold constructing by micro-injection for bone tissue engineering under static magnetic field

Zhengyi Xu,Yujie Zhang,Lang Zheng,He Cai,Xiangjun Yang,Yiyuan Xue,Qianbing Wan,Junyu Chen,Yijun Li

The utilization of static magnetic fields in conjunction with tissue engineering scaffolds has demonstrated significant potential in the restoration of bone defects. However, previous techniques used for fabricating magnetic tissue engineering scaffolds have shown certain shortcomings that require further investigation. In this study, a series of scaffolds made from a combination of polylactic acid (PLA), polycaprolactone (PCL), and iron tetraoxide (Fe 3 O 4 ) nanoparticles were designed and prepared using the microinjection molding technique. The composite scaffolds, which were doped with nanoparticles and fabricated through microinjection, exhibited exceptional physicochemical properties and biocompatibility. Additionally, the PLA/PCL/Fe 3 O 4 scaffolds were found to promote the proliferation and adhesion of bone marrow cells (BMSCs) under relatively low magnetic fields (25–30 mT). These findings suggest that PLA/PCL/Fe 3 O 4 scaffolds hold great potential for use in bone tissue engineering applications.

CAS / MDL: 1317-61-9
研究领域: 生物医学工程 · 材料科学 · 组织工程
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Journal of Biomaterials and Tissue Engineering · 2017 ·Vol. 7 ·期 4 ·283-290 · IF 1.383

The Effect of Porous Sr-Containing Hydroxyapatite on Bone Marrow Mesenchymal Stem Cells and Osteogenesis

Meng Zengdong,Liu Wei,Zhang Yuqin,Zhang Lei,Tang Xu,Lian XingYe,Xie Hui,Li Lei,Wang Chengjian

Hydroxyapatite bioceramics as a kind of bone defect repair and replacement material has been in clinical application for years. In order to further clarify the role of the addition of Sr on the physicochemical properties of these materials, a series of Sr-substituted hydroxyapatites (Sr-HA) were synthesized by high temperature solid state methods and characterized extensively. The proliferation and osteogenesis reactivity of these materials in BMSCs was evaluated, and the behavior towards MG-63 osteoblast cells (in terms of cytotoxicity, proliferation and differentiation assays) was studied. Our results indicated that the addition of Sr does influence the structure of HA, and the crystallinity degree of the materials decreased with Sr addition. The increasing amounts of Sr in the HA composition causes a decrease in the specific surface area and an enrichment of Sr-apatite phase at the surface of the samples. Bioactivity tests show that the presence of Sr did not produce any cytotoxic effect. Moreover, Sr-HA increased the proliferation of BMSCs and MG-63 osteoblast cells and enhanced BMSCs differentiation to osteoblast cells. Thus the Sr-HA is an optimal scaffold material for bone tissue engineering, which can be potentially applied in clinical practice for bone defect repair by compounding with osteoblasts.

研究领域: 材料科学 · 生物材料 · 组织工程 · 细胞生物学
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