Journal of Materials Chemistry B
·
2023
·
IF 7
Dan Wei,Mingze Zeng,Borui Su,Yusheng Zhang,Kai Wu,Ting Zhou,Chengheng Wu,Jing Sun,Hongsong Fan
As one of the physical stimulus tools to target neuromodulation-related biological entities, mild thermal stimulus has attracted increasing attention in unraveling neural differentiation processing. However, thermal stimulus for neural behavior regulation has been relatively unexplored due to the challenge in finding a good method of exerting thermal stimulus. Considering the distance-dependent temperature preservation efficiency and the native importance of a bioactive matrix, we herein put forward the design of a photothermal hydrogel by immobilizing photothermal dopamine (DA) in hyaluronic acid (HA) chains. Benefitting from the minuscule disaccharide repeat unit size (≈1 nm) of HA used for the DA grafting, and the additional adhesion capacity of the DA for recruiting cells, a uniformly close distance from heating source to cells is realized. Therefore, we successfully established a near-infrared light initiated photothermal stimulus platform, with full bioactivity and high thermal manipulation efficiency. After extensive characterization, we proved that the thermal activation, from matrix to cells, triggered TRPV1 ion channel opening and Ca2+ influx, which finally promoted neural differentiation of bone marrow mesenchymal stem cells (BMSCs). This work broadens the possibilities of polymeric photothermal materials, and is of great significance for remotely manipulating neural and other cellular machinery for stem cell therapeutics in tissue engineering.
研究领域:
组织工程
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干细胞生物学
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神经科学
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生物医学工程
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光热治疗
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PubMed
高影响因子
Biomedical Materials
·
2026
·Vol. 21
·期 1
·015022
·
IF 3.9
Liyang Chen,Heng’an Ge,Centao Liu,Jun Li,Chenglong Huang,Biao Cheng
Cartilage defects pose significant clinical challenges due to limited regenerative capacity. Dynamic matrix stiffness, mimicking the physiological mechanical microenvironment, shows promise in directing stem cell chondrogenesis, but its molecular mechanisms remain unclear. Bone marrow mesenchymal stem cells (BMSCs) were cultured on engineered hydrogels with static soft (0.033 kPa), dynamic (0.031–0.126 kPa, time-dependent stiffening), and static stiff (0.126 kPa) conditions. We performed small interfering RNA-mediated Ihh knockdown and Rcan1 overexpression, with chondrogenic differentiation assessed via COL2/SOX9 immunofluorescence. For molecular analyses, we conducted qPCR, CUT&Tag-PCR, Western blot, RNA-seq, H3K18la-targeted CUT&Tag sequencing, and transmission electron microscopy (TEM) for mitochondrial morphology assessment. Dynamic stiffness significantly enhanced chondrogenic differentiation, as evidenced by immunofluorescence detection of elevated COL2 and SOX9 expression. Ihh mRNA expression levels were upregulated by dynamic stiffness. Transcriptome profiling analysis revealed that Ihh knockdown disrupted the expression of genes involved in the glycolytic pathway, while Western blot results showed that Ihh knockdown inhibited histone H3 lysine 18 lactylation (H3K18la). CUT&Tag sequencing revealed Ihh-dependent H3K18la enrichment at regulatory regions of mitochondria-associated genes, notably Rcan1. Ihh deficiency promoted mitochondrial fission, as evidenced by increased Drp1 and Fis1 mRNA expression levels and direct observation of enhanced mitochondrial fission via TEM. Crucially, Rcan1 overexpression rescued mitochondrial fusion, downregulated fission markers, and reinstated chondrogenic marker expression. Consistently, the LDHA inhibitor FX11 reduced lactate levels, diminished H3K18la, and downregulated Rcan1, confirming the metabolic dependence of this axis. RNA-seq analysis further established that Rcan1 overexpression reprogrammed signaling pathways critical for cell differentiation, including ECM-receptor interaction. Dynamic stiffness promotes BMSC chondrogenesis via the Ihh-H3K18la-Rcan1 axis, linking mechanical cues to epigenetic regulation of mitochondrial remodeling and providing a novel target for cartilage repair.
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Biomaterials Science
·
2025
·
IF 5.7
Zihao Zhao,Mengjie Xu,Zhou Zhang,Xing Yin,Ximing Pu,Juan Wang,Xiaoming Liao,Zhongbing Huang,Shunze Cao,Guangfu Yin
The in vitro expanded seed cells and the supraphysiological doses of exogenous growth factors both pose huge safety risks in bone regeneration. In this study, a novel IL-8/tDM/PLGA composite scaffold was developed, where chemokine interleukin-8 (IL-8) and transferable decellularized matrix (tDM) were uniformly overlaid on exterior and interior surfaces of poly(lactic-co-glycolic acid) (PLGA) porous substrates. The in vitro experiments confirmed that the synergy of tDM and IL-8 achieved the obvious promotion of osteogenesis and angiogenesis via enhancing chemotaxis, adhesion, spreading, osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs). IL-8 mediated the in situ recruitment of BMSCs and macrophages via binding with C–X–C motif chemokine receptor 2 (CXCR2), while maintaining cellular viability without inducing macrophage polarization. Moreover, tDM improved BMSC adhesion and spreading via the recognition and binding of the affinitive ligand existing in tDM by the cell adhesion molecules (CAMs) on the BMSC cytomembrane. Furthermore, tDM promoted the osteogenic differentiation and mineralization of BMSCs, benefiting from the retained growth factors. In a rat femoral defect model, the IL-8/tDM/PLGA scaffold significantly accelerated new bone mineralization and maturation through synergistic regulations of cell recruitment, matrix adhesion, and osteogenic signaling pathways. After 8 weeks post-implantation of the IL-8/tDM/PLGA scaffolds, the bone volume fraction of the newly formed bone, trabecular number, and trabecular separation at the defect site were 47%, 1.21 mm−2, and 0.50 mm, respectively, which presented significantly better bone repair effects than those in other groups. These results demonstrated that the innovative bone regeneration strategy combining chemokine-driven recruitment and endogenous tDM regulation offered a potential solution for clinical repair of large-sized bone defects.
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高影响因子
ACS Sustainable Chemistry & Engineering
·
2020
·
IF 7.632
Xihe Zhang,Juan Zhou,Huiyan Ying,Yuting Zhou,Jiahui Lai,Jinghua Chen
Polysaccharides have been considered as an important linker of organics and minerals in the scaffold for bone repair. In this study, we exploited glycogen as the contactor of collagen and hydroxyapatite to form composite hydrogels since it could provide stereoscopic multiple sites for reaction with other components. Glycogen was modified with guanido followed by oxidization to aldehyde, which subsequently combined with collagen and hydroxyapatite through a Schiff base bond and electrostatic interaction, respectively. The resulting hydrogels could almost maintain their prototypes within 2 weeks, with little degradation. Their Young’s modulus (10–70 kPa) and compressive modulus (30–432 kPa) were all within the range of properties required for stem cells to differentiate into osteoblasts or cartilage. Additionally, bone mesenchymal stem cells cultured on the composite hydrogels presented desirable cell adhesion, viability, and growth. The ratio of collagen/glycogen/hydroxyapatite (HAP) components could regulate bone mesenchymal stem cell differentiation into osteoblasts or chondrocytes, which was confirmed by alkaline phosphatase (ALP) activity and related gene expression assays. The results demonstrated that glycogen could be a promising coupling agent for bone scaffold and the collagen/glycogen/nano-HAP (C/G/H) composite hydrogels would be a potential scaffold for bone tissue engineering.
研究领域:
生物材料
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组织工程
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干细胞生物学
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生物医学工程
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高影响因子
Regenerative Therapy
·
2023
·
IF 4.3
Yi Zhou,Guozhen Deng,Hongjiang She,Fan Bai,Bingyan Xiang,Jian Zhou,Shuiqin Zhang
Introduction The repair of bone defects is ideally accomplished with bone tissue engineering. Recent studies have explored the possibility of functional modification of scaffolds in bone tissue engineering. We prepared an SF-CS-nHA (SCN) biomimetic bone scaffold and functionally modified the scaffold material by adding a polydopamine (PDA) coating loaded with exosomes (Exos) of marrow mesenchymal stem cells (BMSCs). The effects of the functional composite scaffold (SCN/PDA-Exo) on BMSC proliferation and osteogenic differentiation were investigated. Furthermore, the SCN/PDA-Exo scaffolds were implanted into animals to evaluate their effect on bone regeneration. Methods SCN biomimetic scaffolds were prepared by a vacuum freeze-drying/chemical crosslinking method. A PDA-functionalized coating loaded with BMSC-Exos was added by the surface coating method. The physical and chemical properties of the functional composite scaffolds were detected by scanning electron microscopy (SEM), energy spectrum analysis and contact angle tests. In vitro, BMSCs were inoculated on different scaffolds, and the Exo internalization by BMSCs was detected by confocal microscopy. The BMSC proliferation activity and cell morphology were detected by SEM, CCK-8 assays and phalloidin staining. BMSC osteogenic differentiation was detected by immunofluorescence, alizarin red staining and qRT‒PCR. In vivo, the functional composite scaffold was implanted into a rabbit critical radial defect model. Bone repair was detected by 3D-CT scanning. HE staining, Masson staining, and immunohistochemistry were used to evaluate bone regeneration. Results Compared with the SCN scaffold, the SCN/PDA-Exo-functionalized composite scaffold had a larger average surface roughness and stronger hydrophilicity. In vitro, the Exos immobilized on the SCN/PDA-Exo scaffolds were internalized by BMSCs. The BMSC morphology, proliferation ability and osteogenic differentiation effect in the SCN/PDA-Exo group were significantly better than those in the other control groups (p < 0.05). The effects of the SCN/PDA-Exo functional composite scaffold on bone defect repair and new bone formation were significantly better than those of the other control groups (p < 0.05). Conclusions In this study, we found that the SCN/PDA-Exo-functionalized composite scaffold promoted BMSC proliferation and osteogenic differentiation in vitro and improved bone regeneration efficiency in vivo. Therefore, combining Exos with biomimetic bone scaffolds by functional PDA coatings may be an effective strategy for functionally modifying biological scaffolds.
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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PubMed
高影响因子
Drug Design Development and Therapy
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2022
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IF 4.319
Yu Li,Ximei Wang
Purpose High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment.Materials and Methods Cell viability was detected by cell counting kit 8 assay and 5-ethynyl-2’-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability.Results Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway.Conclusion Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.
研究领域:
细胞生物学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
Stem Cells International
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2018
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IF 3.989
Jiheng Zhan,Jianbo He,Meihui Chen,Dan Luo,Dingkun Lin
Bone marrow-derived mesenchymal stem cells (BMSCs) are considered as transplants for the treatment of central nervous system (CNS) trauma, but the therapeutic effect is restricted by their finite mobility and homing capacity. Fasudil (FAS), a potent Rho kinase inhibitor, has been reported to alleviate nerve damage and induce the differentiation of BMSCs into neuron-like cells. However, the effect of FAS on the migration of BMSCs remains largely unknown. The present study revealed that FAS significantly enhanced the migration ability and actin stress fiber formation of BMSCs in vitro with an optimal concentration of 30 μmol/L. Moreover, we found that activation of the MAPK signaling pathway was involved in these FAS-mediated phenomena. In vivo, cells pretreated with FAS showed greater homing capacity from the injection site to the spinal cord injury site. Taken together, the present results indicate that FAS acts as a promoting factor of BMSC migration both in vitro and in vivo, possibly by inducing actin stress fiber formation via the MAPK signaling pathway, suggesting that FAS might possess synergistic effect in stem cell transplantation of CNS trauma.
研究领域:
神经科学
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干细胞生物学
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药理学
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PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 25
·4810-4822
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IF 7.571
Boyou Zhang,Fei Sun,Yi Lu,Zhihao Wang,Zhiming Shen,Lei Yuan,Qiang Wu,Cong Wu,Hongcan Shi
Long segment trachea defects are repaired by tracheal substitution, while decellularized technology has been effectively employed to prepare tissue engineering trachea (TET). However, its clinical application is restricted by the long preparation cycle, while poor vascularization is associated with the transplantation failure. In the present study, we used sodium lauryl ether sulfate (SLES) to develop a novel rapid decellularized tracheal preparation method, then constructed a TET with revascularization functions. Summarily, we decellularized rabbit trachea using various SLES concentrations. Results from histological analysis, immunohistochemical and DAPI staining, as well as DNA quantitative assay, revealed that 1–0.1% (v/v) SLES treatment not only entirely removed cellular components to reduce its immunogenicity, but also retained the tracheal matrix's gross structure. SEM images, safranine O-fast green staining, total collagen content assay and collagen II immunofluorescence revealed that low SLES concentrations preserved the bioactive components of the decellularized tracheal matrix. Next, we performed cytobiocompatible and cytotoxin assays to verify biocompatibility of the decellularized tracheal matrix, and is confirmed by the omentum transplantation of rats. Results from omentum transplantation revealed that the decellularized tracheal matrix had low immunogenicity and excellent biocompatibility. Its revascularization capacity was confirmed by histologic appearance and CD31 immunofluorescence. Based on these findings, we selected 0.1% (v/v) as the optimal SLES concentration for preparing a decellularized tracheal matrix. Next, we seeded allogeneic bone marrow stem cells (BMSC) onto the matrix to construct TET patches. In vivo tracheal defect reconstruction confirmed the biocompatibility and revascularization capacity of this novel TET, and the formation of a vascular network around the patch promoted submucosa and mucosa regeneration without significant stenosis, 4 weeks post-surgery. In conclusion, we used SLES to successfully develop a novel decellularized approach for the preparation of TET, which has low immunogenic and inflammatory responses, as well as excellent biocompatibility, and revascularization ability in vivo without additional exogenous cytokines.
研究领域:
组织工程
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再生医学
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生物医学工程
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移植学
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PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 30
·期 2
·1-15
·
IF 3.4
Jingxia Du,Yibo Dong,Jingjing Song,Hanqi Shui,Chengyao Xiao,Yue Hu,Shiyao Zhou,Shanshan Wang
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p in vitro. The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPS‑stimulated macrophages in vitro, and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
研究领域:
心脏病学
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分子生物学
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干细胞研究
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炎症
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外泌体治疗
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PubMed
高影响因子
Collagen and Leather
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2024
·Vol. 6
·期 1
·1-14
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IF 0
Wang Lili,Zhang Shanshan,Yang Fan,Chen Xian,He Huixia,Liu Zaiman,Xiao Jianxi
The reconstruction of critical-size calvarial defects remains a fundamental challenge. Recombinant collagen has gained significant attention in bone tissue engineering owing to its remarkable bioactivity and non-immunogenicity. Herein, we have for the first time developed a bioactive poly(ethylene glycol)-chondroitin sulfate-triple helical recombinant collagen (PEG-ChS-THRC) hydrogel for enhanced bone regeneration in cranial defects. A simple and mild crosslinking reaction of two-arm polyethylene glycol active ester (NHS-PEG-NHS), adipic dihydrazide modified chondroitin sulfate (ChS-ADH) and triple helical recombinant collagen (THRC) leads to the formation of the PEG-ChS-THRC hydrogel. The hydrogel demonstrates interconnected porous structures, enhanced mechanical strength, diminished swelling ratios and adjustable biodegradability. It possesses exceptional biocompatibility and bioactivity, significantly facilitating cell proliferation, adhesion, migration, and osteogenic differentiation of BMSCs. Micro-computed tomography (micro-CT), magnetic resonance imaging (MRI) and histological characterization of rat models with critical-size cranial defects have consistently demonstrated that the PEG-ChS-THRC hydrogel significantly promotes bone tissues regeneration. The innovative bioactive scaffold provides a remarkably improved remedy for critical-size cranial defects, holding greatly promising applications in the fields of bone tissue regeneration. Graphical Abstract
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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DOI
BULLETIN OF MATERIALS SCIENCE
·
2026
·Vol. 49
·期 4
·225
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IF 2.1
Chen Zhida,Wu Yangpeng,Zhuang Hanjie,Jiang Yuanjie,Huang Guofeng,Cai Taoyi
The repair of osteoporotic bone defects remains highly challenging due to the pathological local microenvironment. Exosomes have shown potential as a cell-free therapeutic approach, but their rapid clearance in vivo limits their efficacy. In this study, we developed an injectable oxidized starch/gelatin composite hydrogel (GEL) based on dynamic Schiff base bonds as an intelligent sustained-release carrier for bone marrow mesenchymal stem cell-derived exosomes (Exos), aiming to provide a potential in vitro strategy for modulating bone metabolism. The hydrogel exhibits rapid gelation, notable shear-thinning, and self-healing properties. In vitro release studies demonstrated that the hydrogel enables sustained release of Exos for over 14 days. The exosome-loaded composite significantly enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells and effectively suppressed RANKL-induced osteoclastogenesis. In summary, the GEL-Exos composite system constructed in this study provides a local and long-term bidirectional regulatory microenvironment for bone metabolism. Although in vivo validation is still needed, this system shows promise for future osteoporotic bone defect repair.
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高影响因子
Advanced Healthcare Materials
·
2025
·
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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PubMed
高影响因子
危险品化学品经营许可证（带存储）