Materials Today Bio
·
2023
·
IF 8.2
Yufeng Ai,Fang Dai,Wenfeng Li,Fancheng Xu,Hanwen Yang,Jianxin Wu,Kaiqiang Yang,Li Li,Fanrong Ai,Li Song
The clinical treatments of bone defects remain a challenge. Hydrogels containing bone marrow mesenchymal stem cells (BMSCs) are extensively used to bone regeneration because of excellent biocompatibility and hydrophilicity. However, the insufficient osteo-induction capacity of the BMSC-loaded hydrogels limits their clinical applications. In this study, bio-active glass (BG) and BMSCs were combined with gelatin methacryloyl (GelMA) to fabricate composite hydrogels via photo-crosslinking, and the regulation of bone regeneration was investigated. In vitro experiments showed that the BG/BMSCs@GelMA hydrogel had excellent cytocompatibility and promoted osteogenic differentiation in BMSCs. Furthermore, the BG/BMSCs@GelMA hydrogel was injected into critical-sized calvarial defects, and the results further confirmed its excellent angiogenetic and bone regeneration capacity. In addition, BG/BMSCs@GelMA promoted the polarization of macrophages towards the M2 phenotype. In summary, this novel composite hydrogel demonstrated remarkable potential for application in bone regeneration due to its immunomodulatory, excellent angiogenetic as well as osteo-induction capacity.
研究领域:
生物材料学
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再生医学
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骨科研究
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Lujie Zong,Qing Wang,Houyi Sun,Qian Wu,Yaozeng Xu,Huilin Yang,Shujun Lv,Liang Zhang,Dechun Geng
Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.
研究领域:
生物医学工程
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药剂学
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骨科
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
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IF 10.2
Ruifang Han,Haiyi Zhou,Xingshan Liang,Siyi He,Xiaoming Sun,Yongge Guan,Yang Song
Endometrium plays a key role in embryo implantation and maintenance of pregnancy. However, to repair endometrial injury is still a challenge. In recent years, hydrogel materials have been widely used as effective support matrices to prevent intrauterine adhesions after endometrial injury. They can also be used as preparation scaffolds for encapsulating MSCs and certain therapeutic drugs. This study aimed to develop a preparation scaffold with high tissue affinity, high viscoelasticity and controlled release for repair of endometrial injury. The scaffold utilized heparin poloxamer (HP) as the matrix material and ε-polylysine (EPL) as the functional excipient to prepare a hydrogel that is suitable for endometrial adhesion and further encapsulate BMSCs. Furthermore, a strategy of the thermo-sensitive EPL-HP hydrogel-encapsulated BMSCs were used for better homing of BMSC after transplantation into the rat endometrial injury model, so as to exert the potential of endometrial regeneration by activating Nrf2 to regulate SDF-1/CXCR4 axis.
研究领域:
生殖医学
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组织工程
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干细胞研究
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DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2024
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IF 4.4
Yanyan Wang,Ruyu Yan,Hai Yang,Ying Liu,Xiupeng Zhong,Sa Liu,Renjian Xie,Li Ren
Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride and dopamine modified gelatin (GelMA-DA) were loaded with chondroitin sulfate (the obtained microgel named GC Ms) or bioactive glass (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms showed good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promoted chondrogenic differentiation of BMSCs, while GB Ms promoted osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms were assembled integrally by bottom-up in situ crosslinking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which showed a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments showed that GC-GB/HM could simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects. This article is protected by copyright. All rights reserved
研究领域:
组织工程
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生物材料
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再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
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2025
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IF 14.3
Kaige Mao,Sengpav Tong,Zhi He,Bo Li,Cunyang Wang,Xiaobin Luo,Zifan Li,Zheng Cao,Yifan Wang,Xianzheng Wang,Chuyue Zhang,Yihao Liu,Jianheng Liu,Xiumei Wang,Zheng Wang
The management of critical-size bone defects remains a significant clinical challenge due to the substantial volume involved and the limitations of current treatment methods such as autologous bone grafting, bone allografts, and metal implants. This study aims to develop a novel bone regeneration material by loading bone marrow stromal cells (BMSCs) microgels onto a 3D-printed scaffold composed of Si₃N₄ nanoparticles and poly (lactic-co-glycolic acid) (PLGA) copolymer. The scaffold was fabricated using high-temperature fused deposition modeling 3D printing technology. The addition of Si 3 N 4 nanoparticles enhanced the scaffold's hydrophilicity, mechanical properties, and biological activity. BMSCs microgels were prepared by encapsulating BMSCs in GelMA hydrogel to enhance cell survival rate and prevent the influence of immune response and mechanical stress. In vitro experiments demonstrated that the PS5@BM scaffold (PLGA scaffold with 5% Si 3 N 4 loaded with BMSCs microgels) significantly promoted osteogenic differentiation of BMSCs, anti-inflammatory effects, and angiogenesis. The in vivo study in rat femoral condyle defect models confirmed that within 8 weeks after surgery, the PS5@BM scaffold effectively improved the immune microenvironment at the bone defect site, thereby promoting bone regeneration and vascularization. Compared with the control group, the PS5@BM group had higher vascular regeneration efficiency and new bone content. The synergistic effect of Si 4+ ions released from the scaffold and paracrine growth factors secreted by BMSCs microgels effectively modulated the immune microenvironment, promoting a favorable environment for bone regeneration. This study provides a promising solution for the treatment of critical bone defects, highlighting the potential of Si 3 N 4 bioceramics in bone tissue engineering.
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DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2019
·Vol. 107
·期 7
·1443-1454
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IF 3.221
Wei Jing,Yiqian Huang,Pengfei Wei,Qing Cai,Xiaoping Yang,Weihong Zhong
The strategy of using conductive materials in regenerating bone defects is attractive, benefiting from the bioelectricity feature of natural bone tissues. Thereby, POP conductive fibers were fabricated by coating polypyrrole (PPY) onto electrospun poly( l -lactide) (PLLA) fibers, and their potentials in promoting osteogenic differentiation of bone mesenchymal stromal cells (BMSCs) were investigated. Different from the smooth-surfaced PLLA fibers, POP fibers were rough-surfaced and favorable for protein adsorption and mineralization nucleation. When electrical stimulation (ES) was applied, the surface charges on the conductive POP fibers further promoted the protein adsorption and the mineral deposition, while the non-conductive PLLA fibers displayed no such promotion. When BMSCs were cultured on these fibers, strong cell viability was detected, indicating their good biocompatibility and cell affinity. In osteogenic differentiation studies, BMSCs demonstrated the strongest ability in differentiating toward osteoblasts when they were cultured on the POP fibers under ES, followed by the case without ES. In comparison with the conductive POP fibers, the non-conductive PLLA fibers displayed significantly weaker ability in inducing the osteogenic differentiation of BMSCs with ES being applied or not. Alongside the differentiation, both the calcium deposition on BMSC/material complexes and the intracellular Ca 2+ concentration were identified the most abundant when BMSCs grew on the POP fibers under ES. These findings suggested that the surface charges of conductive fibers played roles in regulating protein adsorption, ion migration and nucleation, particularly under ES, which contributed much to the increased intracellular Ca 2+ ions, and thus accelerated the osteogenic differentiation of the seeded cells. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
研究领域:
生物材料
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组织工程
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骨再生
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
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2018
·
IF 3.309
Wei Jing,Dawei Zuo,Qing Cai,Guoqiang Chen,Lin Wang,Xiaoping Yang,Weihong Zhong
The strategy of using multipotential stem cells like bone mesenchymal stromal cells (BMSCs) for nerve tissue engineering is proven feasible. The promotion effects on neural transdifferentiation of BMSCs from factors including nerve growth factor (NGF), laminin and electrical stimulation (ES) have been reported, while it is not known if these factors can achieve a strong synergetic impact when the cells are cultured on conductive substrates. In this study, it was identified that any single factor (NGF, laminin, or conductive substrate) combined with ES demonstrated the capacity to induce BMSCs transdifferentiating into neural cells, while the efficiency was found in the order of NGF > laminin > conductive substrate. The combination of any two of the factors would be more efficient in inducing the neural transdifferentiation than individual factor. As expected, the strongest promotion in inducing BMSCs to transdifferentiate into neural cells was identified when BMSCs were cultured on laminin-treated conductive nanofibrous mesh in the presence of NGF and under proper ES simultaneously, showing significant synergetic efficiency from these multiple factors. Studies on the Notch-1 signaling pathway , a main negative regulator of neurogenesis , revealed these factors sharing a similar molecular mechanism in regulating the neural transdifferentiation of BMSCs. The results suggested that satisfactory nerve regeneration might be achievable if these synergetic multiple factors could be involved in nerve guidance conduit design, especially, when BMSCs were applied as co-implanted cells.
研究领域:
组织工程
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神经科学
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干细胞生物学
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生物医学工程
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DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2026
·
IF 5.8
Xuekun Fu,Shaochuan Huo,Chunhao Cao,Hanson Hsu,Jie Huang,Yuhe Lei,Jie Li,Peng Liu,Jincheng Zeng,Songqing Lin,Chao Liang
Background Mesenchymal stem cell (MSC) dysfunction contributes to impaired bone regeneration in osteoporosis. Lamin B1, a nuclear lamina protein implicated in stem cell aging, has an unclear role in osteogenesis. Methods We examined Lamin B1 expression during osteogenic differentiation, assessed its pathological alterations in OVX-derived BMSCs, and generated Lamin B1–knockout MSCs to evaluate effects on osteogenesis, migration, and KAT2A regulation. We performed transcriptomic profiling and intra–bone marrow transplantation in OVX mice to determine functional relevance. Results Lamin B1 expression progressively decreased during osteogenic induction but was markedly upregulated in OVX BMSCs, where it correlated with impaired migration. Lamin B1 deletion enhanced alkaline phosphatase activity, mineralization, and migration. Mechanistically, Lamin B1 interacted with KAT2A and promoted its ubiquitin-dependent degradation, thereby reducing KAT2A protein stability. Knockdown-induced transcriptional changes indicated activation of osteogenic and migration-related pathways. In vivo , Lamin B1-deficient MSCs showed improved engraftment and substantially enhanced bone regeneration, reflected by increased BMD, BV/TV, MAR, and BFR in OVX mice. Conclusion Lamin B1 depletion enhances BMSC osteogenesis by preventing KAT2A degradation. Lamin B1-deficient BMSCs provide a promising gene-enhanced cell therapy strategy for osteoporosis.
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2016
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IF 3.42
Qian Li,Dongming Xing,Lie Ma,Changyou Gao
As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between l -lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine.
研究领域:
生物材料学
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再生医学
·
组织工程
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DOI
PubMed
高影响因子
TISSUE & CELL
·
2024
·
IF 2.7
Xiuchao Shang,Yesheng Jin,Yuan Xue,Xiaoyun Pan,Haiquan Zhu,Xiangsheng Meng,Zhihai Cao,Yongjun Rui
This study aimed to investigate the effects of E26-transformation-specific variant-2 (ETV2) overexpression on wound healing in a cutaneous wound (CW) model and clarify associated mechanisms. pLVX-ETV2 lentivirus expressing ETV2 was constructed and infected into BMSCs to generate ETV2-overexpressed BMSCs (BMSCs+pLVX+ETV2). The RT-PCR assay was applied to amplify ETV2, VE-cadherin, vWF, ARG-1, IL-6, iNOS, TGF-β, IL-10, TNF-α. Western blot was used to determine expression of VE-cadherin and vWF. ETV2 induced differentiation of BMSCs into ECs by increasing CDH5/CD31, triggering tube-like structures, inducing Dil-Ac-LDL positive BMSCs. ETV2 overexpression increased the gene transcription and expression of VE-cadherin and vWF (P<0.01). Transcription of M1 phenotype specific iNOS gene was lower and transcription of M2 phenotype specific ARG-1 gene was higher in the RAW264.7+BMSCs+ETV2 group compared to the RAW264.7+BMSCs+pLVX group (P<0.01). ETV2 overexpression (RAW264.7+BMSCs+ETV2) downregulated IL-6 and TNF-α, and upregulated IL-10 and TGF-β gene transcription compared to RAW264.7+BMSCs+pLVX group (P<0.01). ETV2-overexpressed BMSCs promoted wound healing in CW mice and triggered the migration of BMSCs to the wound region and macrophage activation. ETV2-overexpressed BMSCs promoted collagen fibers and blood vessel formation in the wound region of CW mice. In conclusion, this study revealed a novel biofunction of ETV2 molecule in the wound healing process. ETV2 overexpression in BMSCs promoted wound healing in CW mice by triggering BMSCs differentiation into endothelial cells and modulating the transformation of M1 pro-inflammatory and M2 anti-inflammatory macrophages in vitro and in vivo .
研究领域:
细胞生物学
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分子生物学
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伤口愈合
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干细胞研究
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免疫学
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DOI
PubMed
高影响因子
Materials Today Communications
·
2026
·
IF 4.9
Na Qiang,Tao Zhu,Lihong Huang,Wenlong Zhang,Peishi Hu,Jiayi Lu,Xuefeng Zhang,Qingyun Tang,Guocong Liu,Qiang Lin,Shuo Tang
Bone tissue engineering requires biomaterials capable of bionically simulating the physiological electro-microenvironment of natural bone to regulate osteogenic cell behavior. Herein, Ti 3 C 2 T x MXene/P(VDF-TrFE) electroactive nanocomposite membranes with tunable surface potential were successfully fabricated via electrospinning technology. The microstructure, crystal phase composition, thermal stability, piezoelectric performance, and electrical conductivity of the composite membranes were systematically characterized using Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy (Raman), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), piezoelectric coefficient (d 33 ) measurements, and surface resistance tests. XRD, FTIR, and Raman characterizations confirmed that MXene acted as a nucleating agent, which inhibited the formation of the α-phase of P(VDF-TrFE) and promoted the generation of the ferroelectric β-phase. Piezoelectric and electrical property tests demonstrated that MXene doping significantly enhanced the piezoelectric performance and electrical conductivity of the composite membranes. Specifically, the d33 value of the composite membrane with 2.0 wt% MXene reached 5.4 pC/N. Moreover, the surface resistance of MXene-doped membranes was drastically reduced from 230.0 mΩ (for the pure P(VDF-TrFE) membrane) to ∼24–25 mΩ, constructing an efficient charge transport pathway. Consequently, the MXene/P(VDF-TrFE) membranes facilitated cell adhesion, stretching, and proliferation, exhibiting excellent biocompatibility. Meanwhile, cells cultured on the composite membranes displayed enhanced spreading and improved cytoskeletal organization. Further osteogenic assessments revealed that MXene-containing substrates effectively promoted osteogenic differentiation at both the early and late stages, as well as enhanced the formation of mineralized extracellular matrix. These findings suggest that MXene incorporation provides a favorable microenvironment for directing the osteogenic differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs). The fabricated MXene/P(VDF-TrFE) nanocomposite membranes possess a biomimetic microenvironment with sustainable electric potential and optimal topographical structure, offering an innovative and well-suited strategy for applications in bone regeneration.
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DOI
高影响因子
ORAL DISEASES
·
2023
·
IF 3.8
Jiaxin Lv,Qiaona Wang,Dongyu Liu,Catherine Huihan Chu,Heyang Zhou,Guoqing Li,Jin Wu,Kunzhan Cai,Chunbo Tang
Objectives Diabetes mellitus (DM) induces oxidative tissue impairment and suppresses bone formation. Some studies have shown that phytic acid has antioxidant and anti-diabetic properties. This study aimed to investigate the potential of calcium phytate (Ca-phytate) to reverse inhibited osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) in a high glucose (HG) environment and to determine the underlying mechanism. Materials and Methods hBMSCs were exposed to HG and palmitic acid to simulate DM in vitro. Osteogenic differentiation was measured using alkaline phosphatase staining and activity assay, alizarin red S staining, qRT-PCR, Western blot and immunofluorescence staining. A critical-size cranial defect model of type 2 diabetes mellitus (T2DM) rats was established to evaluate bone regeneration. A specific pathway inhibitor was used to explore whether the MAPK/JNK pathway was involved. Results Treatment with 34 μM Ca-phytate had the highest effect on osteogenic differentiation in HG. Ca-phytate improved cranial bone defect healing in T2DM rats. The long-term HG environment inhibited the activation of the MAPK/JNK signalling pathway, which was restored by Ca-phytate. Blocking the JNK pathway reduced the Ca-phytate-mediated osteogenic differentiation of hBMSCs. Conclusion Ca-phytate induced bone regeneration in vivo and reversed HG-inhibited osteogenesis of hBMSCs in vitro via the MAPK/JNK signalling pathway.
研究领域:
医学
·
细胞生物学
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内分泌学
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DOI
PubMed
高影响因子
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