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BIOMATERIALS · 2026 · IF 13.6

Artificial human stem cell niche created in cartilage-inspired hydrogel for enhanced articular cartilage regeneration

Zheyuan Zhou,Yixuan Hou,Ziyang Yao,Qian Han,Siqi Wang,Hua Mei,Haobin Chen,Bo Tian,Ming Li,Lamei Cheng,Chao Zeng,Zhuxin Dong

Stem cell-based therapies and liposome-integrated hydrogel matrix strategies are promising for articular cartilage regeneration. However, challenges persist due to the loss of stemness during in vitro expansion and the lack of control over stem cell behavior in vivo . Herein, we design a cartilage-inspired hydrogel scaffold similar to the native stem cell niche and expect to enhance chondrogenesis for cartilage repair. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are encapsulated within a composite hydrogel composed of methacrylate hyaluronic acid and collagen networks, mimicking the extracellular matrix of native cartilage. Additionally, embedded liposomes participate to form a lubrication mechanism, the boundary layer in the synovial joints, which lowers the coefficient of friction close to the native level. In vitro , our hydrogel niche system enhances cell-cell and cell-matrix interactions, induces hUC-MSCs mesenchymal condensation, establishes the hypoxic microenvironment formation, and therefore improves the chondrogenic differentiation. Moreover, SOX9, COL2, and HIF-1α expression are all upregulated, whereas MMP13 is downregulated. Meanwhile, in vivo implantation in an osteochondral defect model demonstrates our repair strategy is superior to the conventional hydrogel scaffolds. The advantages include the restoration of PRG4, the suppression of MMP13 and the increasement of ICRS II score to the native levels at 6 weeks post-implantation. These findings are important biophysical cues in regulating stem cell fate in a three-dimensional hydrogel niche and conducive to developing biomimetic scaffolds for cartilage repair.

CAS / MDL: 106797-53-9
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Advanced Science · 2026 · IF 14.1

Light-Switched Mesenchymal Stem Cells for In Situ Exosome Amplification in Craniofacial Bone Defect Reconstruction

Tingting Wu,Yajing Liu,Shuman Wang,Xiaoming Bai,Luyun Zhang,Yuwei Liu,Zhiwen Fu,Chen Shi

Mesenchymal stem cell (MSC)-based therapies hold great promise for tissue regeneration, yet precise spatiotemporal regulation of their bioactivity remains challenging. Here, we report a light-switchable MSC system (MSC-UCNPs) enabled by intracellular upconversion nanoparticles (UCNPs), which allowed remote control of exosome biogenesis and regenerative function. Upon 980 nm near-infrared irradiation, intracellular UCNPs emitted localized 365 nm ultraviolet light without compromising MSC viability. The generated UVA stimulus activated the ROS/HEXB/LAMP1 signaling cascade, suppressing lysosome–multivesicular body fusion and thereby markedly enhancing exosome production (increased to 2.7-fold). The MSC-derived exosomes exerted autocrine effects to promote MSC proliferation and osteogenic differentiation, while also facilitating osteoblast maturation via activating the Wnt/β-catenin pathway. To facilitate in vivo application, an injectable hydrogel composed of sodium alginate, calcium alginate, and hyaluronic acid was constructed through electrostatic interactions for the localized delivery of MSC-UCNPs. Positron emission tomography–computed tomography (PET-CT) imaging confirmed the in vivo light-switchable behavior of MSC-UCNPs, allowing on-demand enhancement of in situ exosome release. Benefiting from the synergistic regenerative effects of MSCs and their exosomes, this light-responsive MSC platform achieved robust cranial bone regeneration with a 3.2-fold greater bone volume fraction compared to the control group.

✓ 已验证 DOI PubMed 高影响因子
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Nanomedicine-Nanotechnology Biology and Medicine · 2026 · IF 4.3

Nebulized delivery of multi-modular stem cell-derived exosomes for the treatment of pulmonary fibrosis

Xiaoyu Gao,Chunbin Sun,Yang Yang,Luping Li,Shuang Sha,Shanglin Cai,Liang Li,Zhongci Hang,Lei Wang,Cencan Xing,Hongwu Du

Pulmonary fibrosis (PF) is a terminal pathological manifestation of a group of lung diseases characterized by fibroblast proliferation, excessive extracellular matrix deposition, inflammatory damage, and structural destruction of lung tissue. The lung damage caused by PF is typically irreversible. Current medications and therapies can slow disease progression but fail to fully repair the damaged lung tissue. In this study, we developed a composite nanoparticle system from PNP@Exo using Poly(lactic-co-glycolic) acid (PLGA) as a carrier, which is capable of co-delivering the anti-fibrotic drug nintedanib and coated with polydopamine for adhering human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSCs-Exo) to synergistically harness their therapeutic effects. In vitro experiments demonstrated that the composite drug-loaded nanoparticles PNP@Exo significantly reduced the expression of inflammatory factors, COL I, and COL-III in bleomycin (BLM) induced A549 cells. Furthermore, administration of PNP@Exo into BLM-induced PF mice via nebulization significantly inhibited the production of extracellular matrix components and improved lung function without inducing systemic toxicity. Additionally, PNP@Exo inhibited the ferroptosis process in both PF cells and mice models. In conclusion, the composite drug-loaded nanoparticles synthesized in this study demonstrated a significant therapeutic efficacy in both PF cells and animal models, providing a novel strategy for the treatment of pulmonary fibrosis.

CAS / MDL: 51-61-6
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

Dual-channel constructed polycaprolactone/chitosan/stem cells nanofibers with superior activity for burns and scalds

Hong-Xiang Chu,Run-Ze Shao,Zhi-Wei Zhang,Yue-Han Sun,Ling-Yun Li,Yun-Ze Long,Jun Zhang

Burns and scalds heal slowly due to tissue loss at the wound site and the susceptibility to bacterial infection. Stem cell therapy can compensate for the missing cells at the wound site and promote wound healing. However, the activity of stem cells is easily affected by solvents and high-molecular-weight polymers, which limits the efficacy of stem cell therapy. Here, we developed a compact and portable in situ dual-channel composite electrospinning device. For the first time, this device allowed mesenchymal stem cells (MSCs) to be attached to the surface of polycaprolactone(PCL)/chitosan fibers. The dual-channel design prevents MSCs from contacting the spinning solution directly, thereby overcoming the negative impact of solvents on cell activity and broadening the range of solvents. This advantage is not achievable with conventional electrospinning methods that incorporate MSCs into the spinning precursor solution. The experimental results confirmed that our method combining electrospray and electrospinning enabled uniform dispersion of MSCs among the fibers, and enhanced stem cells survival, promoting their function of stem cells in the wound healing. Further experiments have confirmed that MSCs incorporation endows nanofiber dressings with antibacterial properties and promotes wound healing by inducing the secretion of epidermal growth factor. This combination of stem cell therapy and nanofibers offered a promising new approach for treating burns and scalds, suitable for both outdoor and home emergency handling.

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LANGMUIR · 2026 · IF 4.4

Deep Learning-Assisted Nanomechanical Evaluation of Replicative Senescence in Human Umbilical Cord Mesenchymal Stem Cells

Jinhong Fu,Ruiyu Wang,Qiuyang Deng,Xiyao Yin,Jianjun Dong,Yujuan Chen,Zuobin Wang

The replicative senescence during in vitro expansion severely limits the clinical application of human umbilical cord mesenchymal stem cells (hUC-MSCs). Existing senescence assessment methods still face significant limitations in terms of noninvasive and real-time quantification. In this study, using atomic force microscopy (AFM), we systematically characterized the nanomorphology and mechanical properties of naive and senescent hUC-MSCs. The results revealed that senescent cells exhibited significantly increased height, surface roughness, adhesion, and elastic modulus compared to naive cells, along with enhanced bundling and formation of F-actin stress fibers. These findings show a new “senescence-associated mechanical phenotype” unique to hUC-MSCs. Notably, the hypoxic intervention effectively reversed these senescence-related mechanical changes, demonstrating the high sensitivity of AFM in detecting senescence. To achieve precise quantitative assessment of cell senescence, we also developed a deep learning model based on a variational autoencoder (VAE), which successfully established continuous low-dimensional representations of the age-related mechanical phenotype. This work exhibited excellent predictive performance and generalization ability under different culture conditions, enabling accurate prediction and early identification of hUC-MSCs senescence.

✓ 已验证 DOI PubMed 高影响因子
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POLYMER TESTING · 2026 · IF 6.4

Sustained TGF-β3 delivery and stem cell loading via injectable microspheres enhance cartilage defect repair

Wei Zhan,Hui Deng,Yifeng Xia,Xiao Liu,Jinping You,Fanrong Ai,Jinjun Huang

Microspheres can efficiently load and sustainably deliver growth factors and stem cells. • Microspheres provide a favorable microenvironment that supports chondrogenic differentiation of stem cells. • Injectable microspheres can be applied to irregular and complex cartilage defects in a minimally invasive manner. • Microspheres loaded with stem cells and growth factors offer a new strategy for cartilage defect repair. Cartilage defects severely compromise patients’ quality of life, as the unique structural characteristics of native cartilage endow it with extremely limited self-repair capacity. Mesenchymal stem cells (MSCs) possess tremendous therapeutic potential for cartilage tissue engineering due to their multilineage differentiation capability; however, technical bottlenecks associated with current cell delivery systems greatly restrict their clinical translation. Herein, we fabricated an injectable, multifunctional hydrogel microsphere system (PGCT-MS). Specifically, arginine-glycine-aspartate (RGD) sequences conjugated on gelatin molecules facilitate MSC adhesion, while chondroitin sulfate—an essential component of the chondrocyte extracellular matrix—constructs a favorable microenvironment for MSC spreading. Moreover, polydopamine modification on the microsphere surface enables efficient immobilization and sustained release of transforming growth factor-β3 (TGF-β3), which effectively induces the chondrogenic differentiation of bone marrow MSCs (BMSCs) at cartilage defect sites after in situ injection. In vitro experimental results demonstrated that PGCT-MS significantly enhances BMSC adhesion and chondrogenic differentiation, as verified by the upregulated expression of chondrogenic marker genes, and exhibits excellent adhesion affinity for native cartilage matrices. In vivo animal studies further validated that BMSC-loaded PGCT-MS markedly accelerates high-quality cartilage regeneration. Collectively, this multifunctional therapeutic delivery system provides a promising and feasible strategy for clinical cartilage defect repair.

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Brain Sciences · 2026 ·Vol. 16 ·期 9 ·909 · IF 3.4

Continuous OFT-Based Behavioral Phenotyping Reveals Neural Stem Cell-Associated Shifts in Depression-Like Mice

Han Wang,Zhaoming Liu,Xianjie Li,Lin Fu,Tingxin Lu,Dantong Wang,Guanzhen Lin,Caixia Wu

Background:Depression-like phenotypes in animal models often show graded behavioral variation rather than uniform group-wise changes, yet treatment effects are still commonly evaluated using categorical comparisons. In particular, it remains difficult to determine whether treated animals retain model-like behavioral features or shift toward a more control-like state. Here, we developed a continuous behavioral phenotyping framework based on multidimensional open-field-test (OFT) features to quantify model-like behavioral states and treatment-associated behavioral shifts.Methods:In the present dataset, untreated CUMS- and LPS-induced mice jointly defined a shared model-like behavioral state characterized by reduced locomotor activity and altered spatial exploration. By integrating principal component analysis with k-nearest-neighbor-based behavioral inference, we derived two complementary indices: Δd, representing the relative distance of an animal from the model-like versus control-like behavioral centroids, and p_depression, a kNN-derived score representing similarity to the untreated model-like reference state. These indices were used to position individual animals along a spectrum between control-like and model-like behavioral states.Results:Higher p_depression and lower Δd indicated OFT phenotypes more similar to untreated model mice. Using this framework, NSC-treated animals showed treatment-associated shifts away from model-like behavioral patterns and toward more control-like states, while preserving substantial inter-individual variability. Behavioral scores also showed group-level correspondence with neuroinflammatory markers, suggesting preliminary biological relevance. Because the primary model-specific biological comparisons were based on a limited subgroup size (n= 4 per group), the observed NSC-associated treatment effects should be regarded as exploratory and require confirmation in larger, prospectively powered cohorts.Conclusions:Together, these findings support continuous OFT-based behavioral phenotyping as a promising exploratory approach for evaluating treatment-associated behavioral change and phenotypic heterogeneity in preclinical depression research.

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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Multifunctional bilayer nanofibrous membrane enhances periodontal regeneration via mesenchymal stem cell recruitment and macrophage polarization

Shaoru Wang,Chiyu Li,Shu Chen,Wenyuan Jia,Liping Liu,Yun Liu,Yuheng Yang,Kun Jiao,Yongzheng Yan,Zhiqiang Cheng,Guomin Liu,Zhihui Liu,Yungang Luo

The continuous stimulation of periodontitis leads to a decrease in the number of stem cells within the lesion area and significantly impairing their regenerative capacity. Therefore, it is crucial to promote stem cell homing and regulate the local immune microenvironment to suppress inflammation for the regeneration of periodontitis-related tissue defects. Here, we fabricated a novel multifunctional bilayer nanofibrous membrane using electrospinning technology. The dense poly(caprolactone) (PCL) nanofibers served as the barrier layer to resist epithelial invasion, while the polyvinyl alcohol/chitooligosaccharides (PVA/COS) composite nanofiber membrane loaded with calcium beta-hydroxy-beta-methylbutyrate (HMB-Ca) acted as the functional layer. Material characterization tests revealed that the bilayer nanofibrous membrane presented desirable mechanical strength, stability, and excellent cytocompatibility. In vitro , PCL@PVA/COS/HMB-Ca (P@PCH) can not only directly promote rBMSCs migration and differentiation, but also induce macrophage toward pro-healing (M2) phenotype-polarization with increasing the secretion of anti-inflammatory and pro-healing cytokines, thus providing a favorable osteoimmune environment for stem cells recruitment and osteogenic differentiation. In vivo , the P@PCH membrane effectively recruited host MSCs to the defect area, alleviated inflammatory infiltration, and accelerated bone defects repair. Collectively, our data indicated that the P@PCH nanocomposite membrane might be a promising biomaterial candidate for guided tissue regeneration in periodontal applications.

CAS / MDL: 135236-72-5
研究领域: 生物材料 · 组织工程 · 牙科材料 · 再生医学 · 免疫学 · 干细胞生物学
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SEPARATION AND PURIFICATION TECHNOLOGY · 2025 · IF 9

A pine stem-inspired solar-enhanced lithium recovery system functioned with vapor and salt accumulation

Yang Li,Jun Hou,Jun Guo,Periyasamy Soodamani,Yan Li,Zijun Yang,Yujiao Zhu,Changhao Zhu,Qianqian Zheng

Lithium is a critical strategic while lithium extraction faced with challenges such as slow kinetics and high-water consumption. What's more, high salinity brine has interfering ions hindering the adsorption process. To tackle these problems, a pine stem-inspired tri-functional lithium titanate (Li 4 Ti 5 O 12 , LTO)/ Carbonized aerogel (CA) evaporator (CA@HTO) was synthesized as the key component and integrated into polyethylene (PE) foam platform to create the tri-functional integrated solar evaporator system. On the one hand, the pine xylem-inspired designed aerogel increases water flux, and enriches local Li + supply within aerogel micro channels. On the other, the evaporator shows over 95% solar energy harvesting efficiency to elevate local temperatures, significantly enhancing the endothermic Li + extraction process of lithium-ion sieve (LIS) and solar steam generation. The system doubles the Li + recovery capacity (increasing from 12.66 to 29.12 mg g −1 ) under one-sun illumination, with adsorption kinetics reaching saturation within 6 h—twice the rate observed at 280 K (typical salt-lake temperatures). What's more, the phloem-inspired structure aerogel benefits the directional salt crystallization, which is realized by system design through Marangoni effect. Outdoor solar-powered experiments confirmed the feasibility of stable lithium recovery (>12 mg g −1 ) directly from natural hypersaline salt-lake brines, coupled with self-sustaining water recycling for Li + elution. Salt collection efficiency reaches up to 0.27 kg m −2  h −1 . This work presents an integrated solution for sustainable multiple resources recovery with near-zero water and carbon consumption, contributing to the global target of carbon neutrality.

研究领域: 材料科学 · 环境工程 · 可再生能源 · 可持续资源回收 · 纳米材料
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

A Dynamic Silver–Sulfur/Schiff Base Hydrogel for Delivering Neural Stem Cells in Cerebral Palsy

Simiao Yu,Chenyu Liu,Yongxin Pan,Zhangrong Lou,Weihong Qiao

To address the critical challenges of low cell retention and poor survival in neural stem cell (NSC) transplantation for cerebral palsy, we developed an injectable conductive hydrogel (TT-gel) through dynamic silver–sulfur/Schiff base cross-linking of thiolate oxidized sodium alginate and silk fibroin. The optimized TT-gel demonstrated ideal rheological properties (recovery yield in 40 s > 95%) and electrical conductivity (1.47 ± 0.01 S/m), enabling effective 3D NSC culture with high viability (93.8 ± 1.6% at 5 days) while supporting multilineage differentiation. In a rat cerebral palsy (CP) model, NSC delivery via TT-gel achieved significantly promoted substantial functional recovery, evidenced by 2.6-fold improvement in rotarod endurance and 81.3% reduction in water maze escape latency. Proteomics and histological analysis confirmed enhanced neuroregeneration, showing greater neuronal density and elevated synaptic plasticity markers in treated animals. The therapeutic efficacy of TT-gel stems from its unique dynamic scaffold properties and injectable capability, combined with its electroconductive nature that promotes neuronal differentiation. This multifunctional design collectively addresses the key limitations of conventional NSC transplantation approaches, highlighting its significant clinical potential for CP treatment.

研究领域: 生物医学工程 · 神经科学 · 再生医学 · 生物材料 · 干细胞治疗
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MICROCHEMICAL JOURNAL · 2025 · IF 5.1

Biological characteristics of menstrual blood-derived endometrial stem cell-derived secretome and its therapeutic potential

Yinglei Liu,Guojie Hao,Miaomiao Ma,Haolong Wang,Yu Sun,Wenqiang Zhang,Xingpeng Kang,Haofeng Song,Yilin Lu,Junfang Wu,Wenqiang Fan,Yanli Liu,Juntang Lin

This study aims to systematically characterize the protein and metabolite compositions of the secretome isolated from menstrual blood-derived endometrial stem cell (MenSC-S), elucidate its biological properties, explore potential active components and mechanisms of action as an acellular therapeutic agent, and provide a scientific foundation for advancing its clinical applications. A total of 878 shared proteins were identified in MenSC-S samples from volunteers of varying ages (25, 35, and 45 years), among which 242 were recognized as secretory proteins. The investigation revealed that the key protein heat shock protein family A member 8 (HSPA8) negatively regulates the assembly of the NLRP3 inflammasome complex by activating the PI3K-Akt signaling pathway. Untargeted metabolomic analysis indicated that metabolites present in MenSC-S play significant roles in biological processes such as nitrogen metabolism, amino acid synthesis, and detoxification. Integrated protein-metabolite analysis highlighted the considerable complexity of both proteome and metabolome along with their synergistic effects. Dialysis experiments confirmed that the metabolite fractions within MenSC-S are crucial for enhancing cell viability in both normal cells and those damaged by Cisplatin. This study partially elucidates the biological properties of MenSC-S along with potential molecular mechanisms underlying its therapeutic effects. It not only identifies specific potential active components for developing acellular therapeutic strategies targeting various diseases based on MenSC-S but also establishes a foundation for further exploration into the clinical translation of mesenchymal stem cells (MSCs) and their derivatives.

研究领域: 干细胞生物学 · 再生医学 · 分子生物学 · 免疫调节 · 代谢组学 · 药理学 · 转化医学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Mesenchymal Stem Cell Protection and Chondrogenic Differentiation in Tracheal Fistula Therapy via Bioactive Platinum Nanozymes

Liyong Shi,Wei Ji,Qionghua Zheng,Xiaoyang Chen,Huanran Shen,Guoying Zhang,Shaobin He,Wei Chen,Yi-Ming Zeng

Stem cells are highly regarded in regenerative medicine for their ability to promote wound healing and tissue regeneration, exhibiting great potential for tracheal fistula (TF) repair. However, excessive reactive oxygen species (ROS) at damaged TF sites compromise stem cell viability, differentiation, and functional capacity. This challenge is particularly pronounced due to the limited intrinsic healing potential of the tracheal cartilage, which further complicates effective TF repair. Herein, we report the use of a sodium hyaluronate-platinum nanoparticle composite (SHA-PtNPs) to promote fistula healing while supporting the protection and chondrogenic differentiation of adipose-derived stem cells (ADSCs). In vitro experiments demonstrated that SHA-PtNPs significantly enhanced ADSCs’ viability, migration, ROS scavenging, and anti-inflammatory activity. Under oxidative stress conditions, SHA-PtNPs promoted chondrogenic differentiation, as evidenced by upregulated expression of SRY-box transcription factor 9 (SOX-9), collagen type II alpha 1 chain (COL2A1), and aggrecan (ACAN). Strikingly, the combination of SHA-PtNPs and ADSCs achieved 100% healing by day 14 and facilitated cartilage regeneration, as confirmed by green fluorescent protein (GFP) labeling, verifying ADSC integration. Additionally, SHA-PtNPs-ADSCs reduced ROS levels and inhibited the NF-κB/IκBα/IL-1β signaling pathway, highlighting their potent antioxidative and anti-inflammatory effects. These findings underscore the potential of bioactive platinum (Pt) nanozymes to enhance mesenchymal stem cell protection and chondrogenic differentiation in TF therapy.

CAS / MDL: 16941-12-1
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