Journal of Functional Foods
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2024
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IF 3.8
Xilin Jiang,Jian Tang,Zhiqiang Gao,Caixia Chen,Wenjun Li,Lu Peng,Hongwei Li,Hongying Zhao,Yun Zhao
Moringa oleifera Lam. ( M. oleifera ) has been used as a remedy for diabetes clinically. To discover the underlying mechanism, we investigated its hypoglycemic compounds and shed light on its regulatory targets and pathways using network pharmacology. A total of 13 active compounds of stem were shot, and they may relieve diabetes through 122 core intersecting targets, mainly regulating the biological processes of inflammatory response and apoptosis. Molecular docking showed binding advantages of the active compounds with proteins in apoptosis process. In experiments conducted on MIN6 cells, an islet β-cell line, the extract of M. oleifera stem was validated to protect cells from apoptosis through reducing cellular ROS and endoplasmic reticulum stress. And consistently with its protective effect on islet β-cells, M. oleifera stem alleviated hyperglycemia in Type 2 diabetes mellitus (T2DM) mice. These results offer novel evidence for the development of functional foods to treat T2DM with M. oleifera stem.
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Small
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2024
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IF 13
Junwu Wang,Yilong Huang,Tian Luan,Pengzhi Shi,Lanhong Guo,Qi Zhang,Guang Shi,Zhuowen Hao,Tianhong Chen,Liang Zhang,Jingfeng Li
Depletion of nucleus pulposus-derived stem cells (NPSCs) is a major contributing factor to the attenuation of endogenous regenerative capacity in intervertebral disc degeneration (IVDD). Introducing a hydrogel drug delivery system is a potential strategy for counteracting endogenous cell depletion. The present study proposes a delivery platform for the spatiotemporal release of multiple drugs by combining sodium alginate hydrogels with gelatin microgels (SCGP hydrogels). The SCGP hydrogels facilitated the initial release of chondroitin sulfate (ChS) and the gradual release of an independently developed parathyroid hormone-related peptide (P2). The combined action of these two small molecule drugs “awakened” the reserve NPSCs, mitigated cell damage induced by H 2 O 2 , significantly enhanced their biological activity, and promoted their differentiation toward nucleus pulposus cells. The mechanical and viscoelastic properties of the hydrogel are enhanced by physical and chemical dual cross-linking to adapt to the loading environment of the degenerated disc. A rat IVDD model is used to validate that the SCGP hydrogel can significantly inhibit the progression of IVDD and stimulate the endogenous repair of IVDD. Therefore, the spatiotemporal differential drug delivery system of the SCGP hydrogel holds promise as a convenient and efficacious therapeutic strategy for minimally invasive IVDD treatment.
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ACS Nano
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2025
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IF 16
Xing Zhao,Liya Wang,Ya-Jun Fu,Fei Yu,Kai Li,Yu-Qiang Wang,Yingqiang Guo,Shaobing Zhou,Wei Yang
Intestinal stem cells (ISCs) engage in proliferation to maintain a stable stem cell population and differentiate into functional epithelial subpopulations. This intricate process is upheld by various signals derived from the host and gut microbiota, establishing an ISC niche. However, during inflammatory bowel disease (IBD), this signaling niche undergoes dramatic changes, leading to impaired ISC and hindered restoration of the damaged intestinal epithelial barrier. This study introduces intestinal inflammatory microenvironment-responsive microsphere vehicles designed to remodel the ISC niche, offering an approach to treat IBD. Using an advanced emulsion technique, these microsphere vehicles specifically target colonic inflammation sites, delivering a responsive release of MXene and l-arginine. This delivery system is formulated to modulate intestinal flora and immune responses effectively. l-arginine is converted into nitric oxide to regulate the gut microbiome, while MXene serves as a nanoimmunomodulator to stabilize immune homeostasis. Our findings demonstrate that the anti-inflammatory properties of the microspheres are key to promoting epithelial repair and remodeling of the ISC niche. This study highlights the role of antioxidant microspheres as anti-inflammatory agents that indirectly support ISC function and gut regeneration.
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BIOMATERIALS
·
2024
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IF 12.8
Chuanfeng An,Fei Shao,Canling Long,Yujie Zhang,Wen Nie,Rui Zeng,Zhenzhen Dou,Yuan Zhao,Yuanyuan Lin,Shiying Zhang,Lijun Zhang,Changle Ren,Yang Zhang,Guangqian Zhou,Huanan Wang,Jia Liu
Stem cell therapies have shown great potential for treating myocardial infarction (MI) but are limited by low cell survival and compromised functionality due to the harsh microenvironment at the disease site. Here, we presented a Mesenchymal stem cell (MSC) spheroid-based strategy for MI treatment by introducing a protein/polyphenol self-assembling armor coating on the surface of cell spheroids, which showed significantly enhanced therapeutic efficacy by actively manipulating the hostile pathological MI microenvironment and enabling versatile functionality, including protecting the donor cells from host immune clearance, remodeling the ROS microenvironment and stimulating MSC's pro-healing paracrine secretion. The underlying mechanism was elucidated, wherein the armor protected to prolong MSCs residence at MI site, and triggered paracrine stimulation of MSCs towards immunoregulation and angiogenesis through inducing hypoxia to provoke glycolysis in stem cells. Furthermore, local delivery of coated MSC spheroids in MI rat significantly alleviated local inflammation and subsequent fibrosis via mediation macrophage polarization towards pro-healing M2 phenotype and improved cardiac function. In general, this study provided critical insight into the enhanced therapeutic efficacy of stem cell spheroids coated with a multifunctional armor. It potentially opens up a new avenue for designing immunomodulatory treatment for MI via stem cell therapy empowered by functional biomaterials.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Lan Yang,Wenshuai Li,Kamiran Aihemaiti,Guangwei Jiang,Wenjia Gao,Hongyuan Li,Rongqin Huang
The limited immunogenic cell death (ICD) in tumors, particularly the difficulty in inducing pyroptosis, along with the persistence of breast cancer stem cells (BCSCs), lead to treatment resistance, relapse and metastasis in triple-negative breast cancer (TNBC). To counter these issues, a dual-drug nanoparticle was created by optimizing the encapsulation of clinical decitabine (DCT) and doxorubicin (DOX) into poly(lactic-co-glycolic acid) with a hyaluronic acid modification (DD@PH NPs). This platform targeted both TNBC cells and BCSCs via hyaluronic acid mediation. In 4 T1 cells, DCT was firstly and rapidly released from DD@PH NPs with programmed release feature to induce the up-regulation of gasdermin E through DNA demethylation, and then DOX was significantly released in acidic tumor environments to activate caspase-3 via mitochondrial damage. This process synergistically instigates pyroptosis in otherwise pyroptosis-resistant breast cancer cells, thereby enhancing ICD. Furthermore, the dual-drug release could depolymerize and eliminate BCSCs. Critically, this tumor pyroptosis and BCSCs death triggered a potent anti-tumor immune response, in terms of activating dendritic cells and T cells, and polarizing M2-type macrophages into M1-type. This immune response further inhibited both 4 T1 cells and BCSCs. As a result, the synergistic chemoimmunotherapy of DD@PH NPs led to improved therapeutic outcomes. These include significant inhibition of tumor development and metastasis in TNBC, demonstrating the potential from this nanomedicine for efficient TNBC treatment.
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Advanced Science
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2025
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IF 14.1
Ningyan Cheng,Hongyu Sun,Yevheniy Pivak,Christian H. Liebscher
Copper (Cu)-based nanomaterials are one of the most efficient heterogeneous electrocatalysts for the CO 2 reduction reaction. However, their selectivity and stability are strongly determined by their morphology, crystal structure, composition, grain size, grain boundary density, etc. Hence, gaining quantitative insights into their dynamic evolution under synthesis and/or working conditions is critical for developing optimal Cu-based electrocatalysts and unveiling their structure-property relationship. In this work, the possibility of addressing these issues is demonstrated by integrating in situ liquid phase transmission electron microscopy (LP-TEM) with 4D scanning transmission electron microscopy (4D-STEM). Here, the dynamic morphology and phase evolution of Cu nanoparticles during electrodeposition and electrooxidation processes are revealed in liquid. Virtual imaging and selected area electron diffraction provide novel insights into the evolution of defective nanocrystalline Cu nanoparticles during electrodeposition. It is shown that virtual off-axis dark field imaging can be used to map the distribution of Cu 2 O and Cu within partially oxidized Cu nanoparticles, opening new opportunities for quantitatively probing electrocatalysts under operando conditions.
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Biomaterials Advances
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2024
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IF 5.5
Xiaomei Dai,Meijuan Yuan,Yuxia Yang,Mengbo Dang,Jian Yang,Junli Shi,Dianwei Liu,Mingjun Li,Hang Yao,Wenyong Fei
The tendon-bone interface heals through scar tissue, while the lack of a natural interface gradient structure and collagen fibre alignment leads to the occurrence of retearing. Therefore, the promotion of tendon healing has become the focus of regenerative medicine. The purpose of this study was to develop a gradient COL1/ hydroxyapatite (HAp) biomaterial loaded with human amniotic mesenchymal stem cells (hAMSCs). The performance of common cross-linking agents, Genipin, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), and dual cross-linked materials were compared to select the best cross-linking mechanism to optimize the biological and mechanical properties of the scaffold. The optimal COL1/HAp-loaded with hAMSCs were implanted into the tendon-bone rotator cuff interfaces in rats and the effect on the tendon-bone healing was assessed by micro-CT, histological analysis, and biomechanical properties. The results showed that Genipin and EDC/NHS dual cross-linked COL1/HAp had good biological activity and mechanical properties and promoted the proliferation and differentiation of hAMSCs. Animal experiments showed that the group using a scaffold loaded with hAMSCs had excellent continuity and orientation of collagen fibers, increased fibrocartilage and bone formation, and significantly higher biomechanical functions than the control group at the interface at 12 weeks post operation. This study demonstrated that dual cross-linked gradient COL1/HAp-loaded hAMSCs could promote interface healing, thereby providing a feasible strategy for tendon-bone interface regeneration.
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Biomaterials Research
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2024
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IF 8.1
Xulu Ma,Zhao Luan,Qingxin Zhao,Anli Yang,Jinming Li
Stem cell therapy is an attractive approach to bone tissue regeneration in osteoporosis (OP); however, poor cell engraftment and survival within injured tissues limits its success in clinical settings. Nitric oxide (NO) is an important signaling molecule involved in various physiological processes, with emerging evidence supporting its diverse roles in modulating stem cell behavior, including survival, migration, and osteogenic differentiation. To control and enhance osteogenic differentiation of mesenchymal stem cells (MSCs) for OP therapy, we designed a near-infrared (NIR) light-triggered NO-releasing nanoplatform based on upconversion nanoparticles (UCNPs) that converts 808-nm NIR light into visible light, stimulating NO release by light control. We demonstrate that the UCNP nanoplatforms can encapsulate a light-sensitive NO precursor, Roussin’s black salt (RBS), through the implementation of a surface mesoporous silica coating. Upon exposure to 808-nm irradiation, NO is triggered by the controlled upconversion of UCNP visible light at the desired time and location. This controlled release mechanism facilitates photoregulated differentiation of MSCs toward osteogenic lineage and avoids thermal effects and phototoxicity on cells, thus offering potential therapeutic applications for treating OP in vivo. Following the induction of osteogenic differentiation, the UCNP nanoplatforms exhibit the capability to serve as nanoprobes for the real-time detection of differentiation through enzymatic digestion and fluorescence recovery of UCNPs, enabling assessment of the therapeutic efficacy of OP treatment. Consequently, these UCNP-based nanoplatforms present a novel approach to control and enhance osteogenic differentiation of MSCs for OP therapy, simultaneously detecting osteogenic differentiation for evaluating treatment effectiveness.
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POLYMER
·
2025
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IF 4.5
Chen Wang,Yun Xie,Zhanchi Zhu,Zhaojun Wang,Jiawei Li,Zhaoming Song,Jing Hong,Jingqi Li,Hanmo Zhu,Ying Hao,Guosheng Cheng,Liqiang Luo
Central nervous system (CNS) diseases, characterized by irreversible neuronal damage, pose global health challenges with limited therapeutic options. Stem cell therapy, particularly using neural stem cells (NSCs), is promising with some constraints related to poor microenvironmental simulation. This study presents a composite scaffold integrating three-dimensional graphene foam (3D-GF), GelMA-PEG hydrogel, and mesenchymal stem cell derived small extracellular vesicles (sEVs) to mimic the brain's mechanical and electrical microenvironment while delivering bioactive factors. The hydrogel (<3 kPa) matches brain elasticity (0.5–5 kPa), 3D-GF provides a conductive neural network-like structure, and sEVs enhance neuronal differentiation. In vitro experimental results demonstrated that the NSCs in the composite scaffolds exhibited a proliferation efficiency approximately 7-fold (43.82 ± 2.34 %) higher than that of the control group while the differentiation efficiency was enhanced by 3-fold (49.56 ± 7.80 %). The scaffold's design facilitates mechanical support, electrical signal transduction, and molecular regulation, effectively offering a biomimetic microenvironment. This multi-modal scaffold overcomes traditional limitations, presenting a biomimetic strategy for CNS repair in degenerative diseases.
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MACROMOLECULAR BIOSCIENCE
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2025
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IF 4.1
Hui Liu,Wen Jiang,Lu Han,Xiong Lu
Diabetic chronic wounds exhibit difficulties in healing due to prolonged high glucose and inflammatory conditions. Suppression of inflammation and restoration of the epithelial layer are crucial for preventing infections, reducing moisture loss, and restoring structural and functional integrity to the wound. Currently, there are numerous studies on dressings for diabetic chronic wounds, most of which can inhibit inflammation, but the effect on epithelial regeneration is limited. In this study, we developed a novel therapeutic system utilizing a microporous hydrogel regulated by the natural tea polyphenol EGCG for the treatment of chronic wounds. This hydrogel, made from soy protein isolate and dextran, exhibits anti-inflammatory properties and excellent biocompatibility, and is designed to be both injectable and biodegradable. This hydrogel facilitated the efficient loading and release of human placental stem cell-derived exosomes. Then the exosome-loaded hydrogel was used for full-thickness diabetic skin wound healing. Histological characterization confirmed that the exosome-loaded hydrogel promoted wound healing and epidermal regeneration. Immunofluorescence staining and Western blot experiments demonstrated the anti-inflammatory effect of the hydrogel. In short, this study proposed an Exo-hydrogel therapy as a promising potential for effective treatment of chronic wounds.
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ADVANCED FUNCTIONAL MATERIALS
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2024
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IF 18.5
Huajing Zeng,Ziyan Chen,Pengyu Wei,Haofei Huang,Bin Liu,Zengjie Fan
3D printing of articular cartilage tissue faces challenges like replicating its complex structure, time-consuming in vitro stem cell culture, and a lack of robust in situ regeneration methods for osteochondral defects (OC). In response, an innovative approach utilizing pre-designed bioink modular units for one-step printing and immediate implantation is proposed, circumventing the need for prior in vitro stem cell cultivation. The resulting printed scaffold not only accurately reproduces the three-layer structure and material gradient of articular cartilage tissue but also attains impressive compressive strength (6.3 MPa) through the reinforcement of hydroxyapatite nanofibers and the establishment of chemical bonds with hydrogels. Moreover, the scaffold integrates stem cell capturing and homing layers on its bottom and top layers via chemical crosslinking aptamer and loading poly (lactic-co-glycolic acid) (PLGA) nanospheres encapsulated with stromal cell-derived factor-1α (SDF-1α), respectively. This design enables the specific capture of bone marrow mesenchymal stem cells (BMSCs) in vivo through aptamer interaction, followed by their mobilization to home in on the hyaline cartilage layer via the chemotaxis of SDF-1α concentration gradient. Within the scaffold's microenvironment, these BMSCs undergo differentiation into distinct cells for each layer, effectively contributing to the repair of OC defects in rabbits.
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BIOMATERIALS
·
2024
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IF 12.8
Junjie Tang,Penglei Zhang,Yadong Liu,Dingyu Hou,You Chen,Lili Cheng,Yifang Xue,Jie Liu
Pressure ulcers are a common issue in elderly and medically compromised individuals, posing significant challenges in healthcare. Human umbilical cord mesenchymal stem cells (HUMSCs) offer therapeutic benefits like inflammation modulation and tissue regeneration, yet challenges in cell survival, retention, and implantation rates limit their clinical application. Hydrogels in three-dimensional (3D) stem cell culture mimic the microenvironment, improving cell survival and therapeutic efficacy. A thermosensitive injectable hydrogel (adEHG) combining gallic acid-modified hydroxybutyl chitosan (HBC-GA) with soluble extracellular matrix (adECM) has been developed to address these challenges. The hybrid hydrogel, with favorable physical and chemical properties, shields stem cells from oxidative stress and boosts their therapeutic potential by clearing ROS. The adEHG hydrogel promotes angiogenesis, cell proliferation, and collagen deposition, further enhancing inflammation modulation and wound healing through the sustained release of therapeutic factors and cells. Additionally, the adEHG@HUMSC composite induces macrophage polarization towards an M2 phenotype, which is crucial for wound inflammation inhibition and successful healing. Our research significantly propels the field of stem cell-based therapies for pressure ulcer treatment and underscores the potential of the adEHG hydrogel as a valuable tool in advancing regenerative medicine.
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