ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Cancan Du,Ruiqi Wu,Wenqiang Yan,Jingchao Fang,Wenli Dai,Yiqun Wang,Jin Cheng,Xiaoqing Hu,Yingfang Ao,Xiaolong Liang,Zhenlong Liu
Rotator cuff tear (RCT) is a prevalent shoulder injury that poses challenges for achieving continuous and functional regeneration of the tendon-to-bone interface (TBI). In this study, we controlled the delivery of growth factors (GFs) from liposomal nanohybrid cerasomes by ultrasound and implanted three-dimensional printed polycaprolactone (PCL) scaffolds modified with polydopamine loaded with bone marrow mesenchymal stem cells (BMSCs) to repair tears of the infraspinatus tendon in a lapine model. Direct suturing (control, CTL) was used as a control. The PCL/BMSC/cerasome (PBC) devices are sutured with the enthesis of the infraspinatus tendon. The cerasomes and PCL scaffolds are highly stable with excellent biocompatibility. The roles of GFs BMP2, TGFβ1, and FGF2 in tissue-specific differentiation are validated. Compared with the CTL group, the PBC group had significantly greater proteoglycan deposition (P = 0.0218), collagen volume fraction (P = 0.0078), and proportions of collagen I (P = 0.0085) and collagen III (P = 0.0048). Biotin-labeled in situ hybridization revealed a high rate of survival for transplanted BMSCs. Collagen type co-staining at the TBI is consistent with multiple collagen regeneration. Our studies demonstrate the validity of biomimetic scaffolds of TBI with BMSC-seeded PCL scaffolds and GF-loaded cerasomes to enhance the treatment outcomes for RCTs.
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Materials Science & Engineering C-Materials for Biological Applications
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2020
·
IF 5.88
Naizhen Zhou,Xiaoe Ma,Wanjun Hu,Pengfei Ren,Youliang Zhao,Tianzhu Zhang
The extracellular matrix (ECM) affects cell behaviors, such as survival, proliferation, motility, invasion, and differentiation. The arginine-glycine-aspartic acid (RGD) sequence is present in several ECM proteins, such as fibronectin, collagen type I, fibrinogen, laminin, vitronectin, and osteopontin. It is very critical to develop ECM-like substrates with well-controlled features for the investigation of influence of RGD on the behavior of tumor cells. In this study, poly(ethylene glycol) (PEG)-crosslinked poly(methyl vinyl ether- alt -maleic acid) (P(MVE- alt -MA)) hydrogels (PEMM) with different RGD contents were synthesized, fully characterized, and established as in vitro culture platforms to investigate the effects of RGD content on cancer stem cell (CSC) enrichment. The morphology, proliferation, and viability of SK-OV-3 ovarian cancer cells cultured on hydrogels with different RGD contents, the expression of CSC markers and malignant signaling pathway-related genes, and drug resistance were systematically evaluated. The cell aggregates formed on the hydrogel surface with a lower RGD content acquired certain CSC-like properties, thus drug resistance was enhanced. In contrast, the drug sensitivity of cells on the higher RGD content surface increased because of less CSC-like properties. However, the presence of RGD in the stiff hydrogels (PEMM2) had less effect on the stemness expression than did its presence in the soft hydrogels (PEMM1). The results suggest that RGD content and matrix stiffness can lead to synergetic effects on the expression of cancer cell stemness and the epithelial-mesenchymal transition (EMT), interleukin-6 (IL-6), and Wnt pathways.
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NEUROTOXICITY RESEARCH
·
2020
·Vol. 38
·期 1
·59-73
·
IF 2.992
Wen Caiyan,Huang Cuiqin,Yang Mei,Fan Chongzhu,Li Qin,Zhao Jiayi,Gan Danhui,Li An,Zhu Lihong,Lu Daxiang
Oxidative stress is a potential pathological mechanism of Alzheimer’s disease (AD). Berberine (BBR) can improve antioxidative capacity and inhibit Aβ protein aggregation and tau protein hyperphosphorylation in AD, and stem cell therapy is also increasingly recognized as a therapy for AD. Bone marrow mesenchymal stem cells (BMSCs) have many advantages, as they exhibit antioxidant and anti-inflammatory activity and secrete a variety of neurotrophic factors, and play important roles in neurodegenerative disease treatment. In this study, we investigated the antioxidant effects of secretions from BMSCs pretreated with BBR on tert -butyl hydroperoxide ( t -BHP)–damaged neurons. We demonstrated that BBR can enhance BMSC viability and the secretion of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), both of which are vital neurotrophic factors that maintain neuronal growth. Moreover, conditioned medium from BBR-treated BMSCs (BBR-BMSC-CM) reduced reactive oxygen species (ROS) production, attenuated a decrease in the mitochondrial membrane potential, and ameliorated neuronal apoptosis by decreasing levels of the apoptotic proteins Bax/Bcl-2, cytochrome c, and cleaved caspase-3/caspase-3. In addition, increased synaptophysin (SYP) and postsynaptic density protein 95 (PSD95) levels indicated that neuronal synaptic function was restored. Further study revealed that BBR-BMSC-CM activated the antioxidant proteins Keap1, Nrf2, and HO-1. In conclusion, our results showed that BBR-BMSC-CM attenuated apoptosis and oxidative damage in neurons by activating the Keap1-Nrf2-HO-1 signaling pathway. Taken together, these results also suggest BBR as a drug to stimulate the secretion of nutritional cytokines with the potential to treat AD.
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BIOMATERIALS
·
2016
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IF 8.387
Ping Zhou,Fujian Wu,Tiancheng Zhou,Xiujuan Cai,Siqi Zhang,Xiaohong Zhang,Qiuhong Li,Yongliang Li,Yunfei Zheng,Mengke Wang,Feng Lan,Guangjin Pan,Duanqing Pei,Shicheng Wei
Human pluripotent stem cells (hPSCs) possess great value in the aspect of cellular therapies due to its self-renewal and potential to differentiate into all somatic cell types. A few defined synthetic surfaces such as polymers and adhesive biological materials conjugated substrata were established for the self-renewal of hPSCs. However, none of them was effective in the generation of human induced pluripotent stem cells (hiPSCs) and long-term maintenance of multiple hPSCs, and most of them required complicated manufacturing processes . Polydopamine has good biocompatibility , is able to form a stable film on nearly all solid substrates surface , and can immobilize adhesive biomolecules . In this manuscript, a polydopamine-mediated surface was developed, which not only supported the reprogramming of human somatic cells into hiPSCs under defined conditions, but also sustained the growth of hiPSCs on diverse substrates. Moreover, the proliferation and pluripotency of hPSCs cultured on the surface were comparable to Matrigel for more than 20 passages. Besides, hPSCs were able to differentiate to cardiomyocytes and neural cells on the surface. This polydopamine-based synthetic surface represents a chemically-defined surface extensively applicable both for fundamental research and cell therapies of hPSCs.
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Acta Biomaterialia
·
2024
·
IF 9.4
Sentao Hu,Yangyang Dai,Liaobing Xin,Xiaowen Zheng,Zi Ye,Songying Zhang,Lie Ma
Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. Statement of significance Severe endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.
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Acta Biomaterialia
·
2018
·
IF 6.383
Xiaopeng Zhou,Jingkai Wang,Weijing Fang,Yiqing Tao,Tengfei Zhao,Kaishun Xia,Chengzhen Liang,Jianming Hua,Fangcai Li,Qixin Chen
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. The induction effect of the scaffold on ADSC differentiation was studied in vitro , and a rat coccygeal vertebrae degeneration model was used to investigate the regenerative effect of the CCSA system on the degenerated NP in vivo . The results showed that the CCSA delivery system cross-linked with 0.02% genipin was biocompatible and promoted the expressions of NP-specific genes. After the injection of the CCSA system, the disc height, water content, extracellular matrix synthesis, and structure of the degenerated NP were partly restored. Our CCSA delivery system uses minimally invasive approaches to promote the regeneration of degenerated NP and provides an exciting new avenue for the treatment of degenerative disc disease. Statement of Significance Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Stem cell-based tissue engineering is a promising method in NP regeneration, but there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. Although several research groups have studied the fabrication of injectable hydrogel with biological matrix, our study differs from other works. We chose type II collagen and CS, the two primary native components in the NP, as the main materials and combined them according to the natural ratio of collagen and sGAG in the NP. The delivery system is preloaded with ADSCs and can be injected into the NP with a needle, followed by in situ gelation . Genipin is used as a cross-linker to improve the bio-stability of the scaffold, with low cytotoxicity. We investigated the stimulatory effects of our scaffold on the differentiation of ADSCs in vitro and the regenerative effect of the CCSA delivery system on degenerated NP in vivo .
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lili Wang,Xian Chen,Xiaoyan Wang,Hang Chen,Xiaxia Yang,Jianxi Xiao
Osteochondral defects, caused by trauma, inflammation, or degenerative diseases, lead to joint dysfunction and disability. While biomimetic scaffolds can replicate the complex composition of native osteochondral tissue, they often fail to mimic its intricate and anisotropic nanostructure. In this study, we develop a highly biomimetic three-layer mineralized collagen scaffold featuring a wood-reinforced subchondral bone region (TMCWSB) for osteochondral tissue engineering. The scaffold comprises a superficial zone (SZ) of collagen, a middle zone (MZ) of collagen and hydroxyapatite, and a bottom zone (BZ) of wood, collagen, and hydroxyapatite. The organic content decreases and inorganic content increases progressively from SZ to BZ, closely mimicking the composition of native osteochondral tissue. The scaffold's structure replicates the interconnected porous network in the SZ and the directional pore architecture in the BZ, resembling the natural osteochondral microstructure. With enhanced mechanical properties from SZ to BZ, the TMCWSB scaffold demonstrates exceptional biocompatibility and bioactivity, effectively promoting the gradient differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage-bone phenotypes. This highly biomimetic TMCWSB scaffold offers a promising strategy for osteochondral defect repair and holds significant potential in tissue regeneration and osteoarthritis treatment.
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FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Xuan Zhou,Yingxin Wei,Ziqing Meng,Yiming Feng,Zhaojie Li,Hongwei Zheng,Changhu Xue
This study aims to develop a safe, efficient, and serum-free induction platform for the adipogenic differentiation of adipose-derived stem cells (ASCs) from Larimichthys crocea , to advance the production of cultivated fat for cellular agriculture. Through systematic screening of plant-derived small molecules, bavachinin and dehydroabietic acid were identified as core inducing components, with their concentrations and exogenous lipid supplementation strategies optimised. A serum substitute culture system (SS) was successfully established, comprising growth factors, antioxidants, and carrier proteins, which effectively supports ASCs adipogenesis. Further investigation under three-dimensional culture on gelatin-based porous microcarriers revealed that lower stiffness (10 kPa) enhanced lipid accumulation and adipogenic gene expression. Transcriptomic and metabolomic analyses indicated that the induction system activates the PPARγ pathway and promotes lipid synthesis and accumulation. This work provides a robust chemical biology strategy and theoretical foundation for the scalable production of cultivated fish adipose tissue.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2018
·Vol. 28
·期 11
·1705546
·
IF 13.325
Yi Deng,Shicheng Wei,Lei Yang,Weizhong Yang,Matthew S. Dargusch,Zhi-Gang Chen
Realizing the clinical potential of human induced pluripotent stem cells (hiPSCs) in bone regenerative medicine requires the development of safe and chemically defined biomaterials for expansion of hiPSCs followed by directing their lineage commitment to osteoblasts. In this study, novel multipurpose peptide-presenting hydrogel surfaces are prepared on common tissue culture plates via carboxymethyl chitosan grafting and subsequent immobilization of two functional peptides allowing for in vitro feeder-free culture, long-term self-renewal, and osteogenic induction of hiPSCs. After vitronectin (VN) peptide modification, the engineered surfaces facilitate adhesion, proliferation, colony formation, and the maintenance of pluripotency of hiPSCs up to passage 10 under fully defined conditions without Matrigel or protein coating. Further, this synthetic niche exhibits an appealing regulatory effect on the osteogenic conversion of hiPSCs to osteoblastic phenotype without an embryoid body formation step by co-decoration of different ratios of VN and bone-forming peptide. Such a well-defined, xeno-free 2D engineered microenvironment not only helps to accelerate the clinical development of hiPSCs, but also provides a safe and robust platform for the generation of osteoblast-like cells or bone-like tissues at different maturation levels. Thus, the strategy may hold great potential for application in cell therapy and bone tissue engineering.
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Acta Biomaterialia
·
2019
·
IF 6.638
Jieni Fu,Xiangmei Liu,Lei Tan,Zhenduo Cui,Yanqin Liang,Zhaoyang Li,Shengli Zhu,Yufeng Zheng,Kelvin Wai Kwok Yeung,Paul K Chu,Shuilin Wu
Growing evidence suggests that the physical microenvironment can guide cell fate. However, cells sense cues from the adjacent physical microenvironment over a limited distance. In the present study, murine mesenchymal stem cells (MSCs) and murine preosteoblastic cells (MC3T3-E1) behaviors are regulated by the cell–material interface using ordered-micro and disordered-nano patterned structures on Ti implants. The optimal bone formation structure is a stable wave (horizontal direction: ridge, 2.7 µ m; grooves, 5.3 µ m; and vertical direction: distance, 700 µ m) with the appropriate density of nano-branches (6.0 per µ m 2 ). The repeated waves provide cells with directional guidance, and the disordered branches influence cell geometry by providing different spacing and density nanostructure . And micro-nano patterned structure can provide biophysical cues to direct cell phenotype development, including cell size, shape, and orientation, to influence cellular processes including survival, growth, and differentiation. Thus, the overlaid isotropic and anisotropic cues, ordered-micro and disordered-nano patterned structures, could transfer further and alter cell shape and induce nuclear orientation by activating Wnt/ β -catenin signaling to promote integrin α5, integrin β1, cadherin 2, Runx2, Opn , and Ocn . That canonical Wnt signaling inhibitor dickkopf1 further demonstrates osteogenic differentiation induced by ordered-micro and disordered-nano patterned structures, which is related to Wnt/ β -catenin signaling. Our findings show the role of ordered microstructures and disordered nanostructures in modulating stem cell differentiation with potential medical applications. Statement of significance It remains a challenge to modify poor osteogenic and osteoconductive properties of titanium alloy bases on the inherent poverty of titanium. We demonstrate that ordered microtopography and disordered nano topography pattern structure could lead to osteogenic differentiation in vitro and bone regeneration in vivo . Furthermore, the pattern structure is created through selective laser melting and alkali heat. And the structure only takes advantage of titanium itself and does not bring in active film, such as hydroxyapatite . On the other hand, we find that cell shape and orientation show angle-orientation tendency due to the polarity, which involves with mechanical signal created via patterned structure. Meanwhile, the Wnt/Ca 2+ signaling pathway is activated.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Huanqing Song,Qingfei Hao,Jingjing Li,Yuanyuan Liu,Zhifang Huo,Ranran Si,Xiaoxia Feng,Chuan Zhou,Xiuyong Cheng
Bone marrow-derived mesenchymal stem cell (BMSCs) delivery is a promising therapeutic strategy for bronchopulmonary dysplasia (BPD); however, its efficacy remains suboptimal. Recent studies have reported that extracellular vesicles derived from peroxiredoxin 6 (PRDX6)-downregulated mesenchymal stem cells (MSCs) exhibit diminished anti-inflammatory and anti-oxidant effects through a paracrine mechanism. Nevertheless, whether PRDX6 participates in BPD progression via paracrine signaling remains unclear. Herein, rat BMSCs were first isolated and characterized. The GFP-labeled lentivirus was used to overexpress PRDX6 in BMSCs. PRDX6-overexpressing BMSCs exhibited improved proliferation and migration abilities. Notably, mesencephalic astrocyte-derived neurotrophic factor (MANF) secretion was significantly increased (~2.5-fold, p < 0.05) in PRDX6-overexpressed BMSCs. Further mechanistic studies revealed that PRDX6 bound to MANF, reducing its endoplasmic reticulum retention by displacing glucose-regulated protein 78, thereby promoting MANF secretion. Silencing MANF expression markedly attenuated the effects of PRDX6 overexpression. PRDX6-modified BMSCs were delivered intratracheally into BPD rat model, which was established by exposing rats in 85 % oxygen for 21 days. PRDX6 overexpression enhanced BMSCs recruitment to injured lung tissues, and significantly reduced apoptosis, inflammation, vascular loss, and pulmonary arterial remodeling. Concurrently, MANF levels in lung tissues, bronchoalveolar lavage fluid, and serum were elevated post-administration. These results suggest that PRDX6-mediated MANF secretion in BMSCs may not only enhance their proliferative and migratory capacities but also directly protect against lung injury. These findings provide a new strategy for amplifying the in vivo efficacy of BMSCs delivery on BPD.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Haitao Zhang,Chaofeng Chen,Dayu Wang,Yiwei Huang,Yang Liu,Zhiyuan Wang,Furui Fu,Hongyu Wang,Senjie Shi,Yijin Li,Jianchun Zeng,Caiping Shen,Chudan Zhong,Xiaozhou Liu,Jinlun Chen,Jie Li,Shufen Liu,Jin Huang,Yirong Zeng,Wenjun Feng
As an emerging environmental contaminant, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) poses a potential threat to public health. However, the potential link between 6PPD-Q exposure and bone health remains largely unexplored. This study aims to systematically investigate the toxic effects of 6PPD-Q on bone metabolism and elucidate the underlying mechanisms by integrating transcriptomic sequencing, network toxicology, single-cell RNA, Molecular docking, molecular dynamics with both in vivo and in vitro experiments. Integrative analysis converged on mitophagy as a central mechanism in 6PPD-Q-induced osteoporosis, with single-cell sequencing identifying bone marrow-derived mesenchymal stem cells (BMSCs) as the key cell type and revealing CX43, MMP2, PDGFRB, and FYN as the principal targets. Molecular docking and MD simulations confirmed the targeted binding of 6PPD-Q to CX43. RNA-seq analysis of rat tibiae validated the differential expression of CX43 and the critical role of mitophagy. Both in vivo and in vitro experiments demonstrated that 6PPD-Q-induced bone loss was associated with the downregulation of CX43 and concomitant mitophagy dysregulation. In conclusion, this study elucidates that 6PPD-Q induces bone loss was associated with the downregulation of CX43 and concomitant mitophagy dysregulation. Our work establishes a comprehensive mechanistic framework for 6PPD-Q-induced bone damage and offers novel insights for future research into its bone toxicity. The 1 or 10 mg/kg dose used in this study, although higher than the typical environmental exposure level, is consistent with the effects observed in cadmium exposure and is close to the 8 mg/kg dose used in studies on mouse bone toxicity. Additionally, the 5 ng/mL concentration of 6PPD-Q used in the in vitro experiments is comparable to the concentration detected in freshwater, indicating its environmental relevance.
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