COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Yuhan Tu,Yangyang Ning,Hong Wang,Yang Li,Zhiang Yao,Shanhui Tao,Wenjing Yang,Bin Li,Xiaofen Li,Huacheng He,Shijun Li
Rapid and scar-free healing of burn wounds is an urgent clinical issue. Basic fibroblast growth factor (bFGF) has been proven to promote the healing of burn wounds by accelerating ECM remodeling and angiogenesis. However, exudates from burn wounds can accelerate bFGF degradation, thereby affecting its bioactivity. This study proposes an effective protection strategy for bFGF that involves encapsulating bFGF in nanoliposomes (bFGF-NLip) and then incorporating bFGF-NLip into a bovine serum albumin (BSA) hydrogel. This hybrid hydrogel system (bFGF-NLip@B) could maintain the activity of bFGF, achieve sustained release, and allow phospholipids and cholesterol to penetrate the skin, thereby enabling bFGF to function in the dermis. The experimental results showed that the hydrogel was injectable with good mechanical properties and biocompatibility. In a mouse scald wound model, owing to the sustained release of bFGF and skin permeation function of the nanoliposomes, the hydrogel promoted granulation formation, collagen deposition, vascular regeneration, and re-epithelialisation, ultimately accelerating wound healing. In addition, the hydrogel effectively inhibited scar formation. This system provides novel insights into the delivery of bFGF and scar-free healing of burn wounds.
研究领域:
药剂学
·
生物医学工程
·
伤口愈合
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组织工程
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
·
2025
·
IF 8.7
Qi Zhang,Yezhen Tan,Qiyang Liang,Liangyou Gu,Yue Shi,Yan Huang,Xiubin Li,Jie Qi,Cheng Peng,Hanfeng Wang,Yaohui Wang,Kan Liu,Tianwei Cai,Yudan He,Qingbo Huang,Xu Zhang,Baojun Wang,Xin Ma,Weimin Ci
Preoperative downstaging of renal cell carcinoma with a tumor thrombus (RCC-TT) makes thrombectomy feasible. However, treatment resistance is common and may partly be attributed to the tumor-promoting role of the tumor microenvironment (TME). Herein, we sequenced, integrated, and comprehensively analyzed multi-center, multi-omics data from 164 RCC-TT patients and identified two clinically relevant RCC-TT subtypes. We find that the poor-prognosis subtype (TT1) exhibits enhanced extracellular-matrix (ECM) remodeling driven by epithelial LOX expression. Spatial transcriptomics (ST) shows the co-localization of GPNMB + macrophages, THBS2 + fibroblasts, and LOX + malignant cells around tumor nests in TT1 tumors, reinforcing tumor immune barriers (TIBs). Our extensive validations using cell lines, syngeneic mouse models, multiplex immunofluorescence staining, and large-scale RCC cohorts underscore the potential of LOX inhibition in disrupting TIBs, sensitizing RCC to immunotherapy, and overcoming treatment-induced phenotypic plasticity. This study provides insights into the biological underpinnings and prognosis assessment of RCC-TT, demonstrating targetable ECM-remodeling vulnerabilities.
研究领域:
肿瘤学
·
分子生物学
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免疫学
·
生物信息学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yujie Zhang,Yuan Zhao,Chuanfeng An,Yiyang Guo,Yubin Ma,Fei Shao,Yonggang Zhang,Kai Sun,Fang Cheng,Changle Ren,Lijun Zhang,Bingbing Sun,Yang Zhang,Huanan Wang
Recent progress in stem cell therapy has demonstrated the therapeutic potential of intravenous stem cell infusions for treating the life-threatening lung disease of pulmonary fibrosis (PF). However, it is confronted with limitations, such as a lack of control over cellular function and rapid clearance by the host after implantation. In this study, we developed an innovative PF therapy through tracheal administration of microfluidic-templated stem cell-laden microcapsules, which effectively reversed the progression of inflammation and fibrotic injury. Our findings highlight that hydrogel microencapsulation can enhance the persistence of donor mesenchymal stem cells (MSCs) in the host while driving MSCs to substantially augment their therapeutic functions, including immunoregulation and matrix metalloproteinase (MMP)-mediated extracellular matrix (ECM) remodeling. We revealed that microencapsulation activates the MAPK signaling pathway in MSCs to increase MMP expression, thereby degrading overexpressed collagen accumulated in fibrotic lungs. Our research demonstrates the potential of hydrogel microcapsules to enhance the therapeutic efficacy of MSCs through cell-material interactions, presenting a promising yet straightforward strategy for designing advanced stem cell therapies for fibrotic diseases.
研究领域:
干细胞疗法
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肺医学
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生物材料
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免疫学
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组织工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2024
·Vol. 113
·期 1
·e37844
·
IF 3.9
Qibin Han,Yinhua Qian,Lang Bai,Jing Zhou,Yuefeng Hao,Dan Hu,Zhouzhou Zhang,Xing Yang
Tendinopathy is a disorder characterized by pain and reduced function due to a series of changes in injured or diseased tendons. Inflammation and collagen degeneration are key contributors to the onset and chronic nature of tendinopathy. Acetyl-11-keto-β-boswellic acid (AKBA) is an effective anti-inflammatory agent widely used in chronic inflammatory disorders and holds potential for tendinopathy treatment; however, its therapeutic efficacy is limited by poor aqueous solubility. Here, we fabricated AKBA-encapsulated cationic liposome-gelatin methacrylamide (GelMA) microspheres (GM-Lipo-AKBA) using thin-film hydration and microfluidic technology for drug delivery therapy. GM-Lipo-AKBA exhibited high encapsulation efficiency, extended AKBA release for over 4 weeks, and prolonged degradation. In vitro and in vivo experiments demonstrated its effectiveness in improving inflammation and ECM remodeling in tendinopathy. In summary, the injectable nano-micron drug delivery platform provides a promising strategy for the sustained and localized delivery of AKBA for tendinopathy treatment.
研究领域:
药学
·
生物医学工程
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骨科
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药物递送系统
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炎症研究
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Tiantian An,Zhaoyu Xu,Yang Yang,Xinhui Li,Shuaidong Chen,Xingmei Yang,Yi Man,Chen Hu,Yili Qu
This study investigates the role of γδ T cells in wound healing facilitated by an EGCG (Epigallocatechin gallate)-releasing nanofibrous scaffold with aligned topography (APEMS). Incorporating core-shell microcapsules for sustained EGCG release over 11 days, the biocompatible scaffold enhances γδ T cell activity to promote advanced wound repair. In a splinted wound excisional model in 6-8 weeks-old male C57BL/6J mice, APEMS significantly improved re-epithelialization and wound closure compared to a control scaffold (APS). Single-cell RNA sequencing revealed a marked increase in γδ T cell in the APEMS group, where γδ T cells accounted for 66.2% of the T cell population, compared to 33.8% in the APS group. Cellchat analysis identified the AREG-EGFR signaling axis as pivotal to γδ T cell-mediated wound repair. APEMS-induced γδ T cells secreted amphiregulin (AREG), which acted on keratinocytes and fibroblasts to enhance keratinocyte proliferation, migration, and fibroblast-driven extracellular matrix remodeling. In immunodeficient mice lacking mature γδ T cells (TCRδ-/-), wound healing was significantly impaired, characterized by delayed re-epithelialization, reduced neo-dermal thickness, and increased inflammation. Inhibition of AREG and EGFR function via monoclonal antibodies against AREG and EGFR antagonist Gefitinib similarly delayed wound healing, the therapeutic advantage of APEMS over APS was abolished, emphasizing its critical role in the process. These findings provide a framework for developing advanced wound management materials and highlight the therapeutic potential of targeting γδ T cells and AREG-EGFR signaling to enhance tissue regeneration.
研究领域:
生物材料
·
免疫学
·
组织工程
·
再生医学
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药学
·
细胞生物学
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皮肤科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Xiyue Duan,Kepeng Hu,Jiawei Wang,Xiaozhao Wang,Xiaojun Long,Weiming Lin,Chengwei Wu,Wenjian Weng,Zhangfa Song,Kui Cheng
The imbalance of macrophage polarization between M1 and M2 phenotypes in rheumatoid arthritis (RA) results in a persistent inflammatory cascade. Activating M2 anti-inflammatory polarization, which remove excess extracellular matrix (ECM) via phagocytosis, represents a potential therapeutic target for RA. This study introduces Col/Cs@ECM microspheres, a novel drug delivery system designed for macrophage recognition via a tailored ECM surface, enhancing phagocytic efficiency and accumulation. Moreover, the Col/Cs@ECM microspheres are composed of biocompatible and fully degradable materials, ensuring their safety profile within the physiological environment. Following cell phagocytosis, the collagen/chitosan (Col/Cs) core release the drug (Dexamethasone, Dex) intracellularly to inhibit M1 polarization by inhibiting the NF-κB signaling pathway and to facilitate M2 polarization. This macrophage targeted and intracellular release approach offers a significant advantage over traditional medications by reducing systemic side effects and improving the therapeutic index. The strategy prompts macrophages to express anti-inflammatory cytokines like IL-10 while suppressing pro-inflammatory cytokines such as TNF-α, thereby remodeling the immune microenvironment. Additionally, the specially engineered ECM shell of the microspheres extends the anti-inflammatory response by prolonging macrophage lifespan, a feature that is not present in conventional treatments. This results in improved treatment outcomes in an in vivo RA animal model. This research presents a possible intracellular anti-inflammatory treatment approach for rheumatoid arthritis injection therapy with the potential to outperform existing treatments in terms of efficacy and safety.
研究领域:
生物医学工程
·
免疫治疗
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药物递送系统
·
风湿病学
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细胞生物学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Renwen Wan,Zhiheng Lin,Mowen Xu,Wei Luo,Hengjie Jia,Zhufeng Hu,Zhengyuan Fang,Junming Sun,Yisheng Chen,Shiyi Chen,Zhiwen Luo,Lei Yi,Zhijie Zhao
Diabetic wound healing is a significant complication of diabetes mellitus, characterized by prolonged healing times, heightened infection risks, and potential amputations, necessitating innovative therapeutic approaches. This study aims to evaluate the efficacy of a novel injectable hydrogel, AP@HA-Si InjGel, which combines hyaluronic acid, silanol, and bioactive compounds to promote wound healing in diabetic patients. Utilizing a combination of in vitro assays, diabetic mouse models, and advanced techniques such as single-cell RNA sequencing, we demonstrated that AP@HA-Si InjGel significantly accelerates wound closure, enhances collagen deposition, and modulates macrophage polarization towards a pro-healing M2 phenotype while suppressing the inflammatory M1 phenotype. The hydrogel exhibited excellent biocompatibility with over 90 % cell viability and significant antioxidant properties, reducing reactive oxygen species accumulation. Histological analysis confirmed that AP@HA-Si InjGel promoted neovascularization and improved extracellular matrix remodeling, thereby enhancing tissue regeneration. Furthermore, single-cell RNA sequencing revealed distinct macrophage subtypes, with an increased proportion of M2 macrophages and a favorable differentiation trajectory towards enhanced wound healing. Overall, these findings highlight the therapeutic potential of AP@HA-Si InjGel as a comprehensive strategy for diabetic wound management, warranting further exploration in clinical settings to address the growing challenge of impaired wound healing in diabetic patients.
研究领域:
生物医学工程
·
伤口愈合
·
免疫调节
·
糖尿病并发症
·
生物材料
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Wei Chen,Yi Chen,Yiming Ren,Cangjian Gao,Chao Ning,Haotian Deng,Peiqi Li,Yang Ma,Hao Li,Liwei Fu,Guangzhao Tian,Zhen Yang,Xiang Sui,Zhiguo Yuan,Quanyi Guo,Shuyun Liu
Inferior healing and peritendinous adhesions are the major clinical problems following Achilles tendon injury, leading to impaired motor function and an increased risk of re-rupture. These complications are presumed to be inextricably linked to inflammation and fibroscar formation. Here, microRNA29a is identified as a promising therapeutic target for tendon injury through the cross-regulation of the immune response and matrix remodeling. MiR29a-LNPs were successfully prepared by microfluidic technology. They are then loaded into the core-shell nanofibers to achieve local delivery in the injured tendon , where the shell layer is composed of PELA for anti-adhesion. Our studies reveal that miR29a regulates collagen synthesis and NF-κB activation in tenocytes , and promotes macrophage polarization by inhibiting the inflammasome pathway. In vivo studies of the Achilles tendon-rupture model indicate the best repair in the miR29a group, as evidenced by superior collagen composition and alignment, higher mechanical strength , and better functional recovery. In conclusion, a functionalized anti-adhesive membrane that promotes nascent tendon matrix remodeling and improves the regenerative immune microenvironment is developed for the treatment of tendon injury.
研究领域:
生物医学工程
·
组织工程
·
再生医学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Jihua Wei,Zichun Song,Jiuying Cui,Yuanxun Gong,Qianli Tang,Kai Zhang,Xinlei Song,Xianjiu Liao
In the current study, a novel electrochemiluminescence biosensor based on the entropy-driven DNA tetrahedron for the detection of matrix metalloproteinase 2 (MMP2), an enzyme that regulates extracellular matrix remodeling and affects aging was reported. The biosensor utilizes an inverted DNA tetrahedron structure, which exposes three vertices to the solution, as molecular recognition units for capturing specific biomolecules. The biosensor also employs a ratiometric method and an entropy-driven reaction, which enhance the response rate and sensitivity of the detection. The biosensor can detect MMP2 with a detection limit of 55.2 fM, which is lower than that of conventional sensors. The biosensor also exhibits excellent stability and reproducibility, and can accurately measure MMP2 levels in complex samples, such as human serum. The paper demonstrates the feasibility and effectiveness of using the “inverted” DNA tetrahedron structure and the entropy-driven process to construct interfacial biosensors. The paper also discusses the potential applications of the biosensor in clinical diagnosis and anti-aging research, where MMP2 plays a crucial role in tissue damage and repair. The paper provides a valuable contribution to the field of biosensor development, and opens up new possibilities for using DNA nanotechnology for sensitive and reliable detection of various biomolecules.
研究领域:
生物传感器开发
·
DNA纳米技术
·
衰老研究
·
临床诊断
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-16
·
IF 16.6
Wei Zhao,Lei Meng,Wang Yaohui,Xie Yizhou,Xie Xueyong,Lan Dongwei,Jia Yuanbo,Liu Jingyi,Ma Yufei,Cheng Bo,Gerecht Sharon,Xu Feng
The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion.
研究领域:
生物材料
·
组织工程
·
细胞生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Jiaqi Xu,Nanfang Nie,Bingbing Wu,Yu Li,Lin Gong,Xudong Yao,Xiaohui Zou,Hongwei Ouyang
Although biomaterials are widely utilized in clinics, it still follows the “one-fits-all” strategy. Biological variables such as age and sexuality have an impact on the host immune response and are not fully considered in the practice guidelines of the biomaterial implantation . In this study, we investigated the immuno-material interactions of six commonly used biomaterials (agarose, alginate , chitosan, CMC , GelMA and collagen type I) and constructed a population (with different ages and sexes) based transcriptome atlas. Protein and polysaccharide-based biomaterials elicited distinctive immune responses that protein-based materials preferred the NKT pathway to activate innate and adaptive immune response, whereas polysaccharide-based materials activated the cDCs to present antigen. The atlas further revealed the sex/age-related variabilities on the immune response followed by the polysaccharide treatment. As for sex bias, alginate and agarose stimulation significantly increased the proportion of naive CD4 + T cells in the female group, accompanied by the Th1 differentiation tendency, compared to the male group. Age-biased transcript showed alginate and chitosan would impair the extracellular matrix remodeling and up-regulate the apoptosis process in the elderly groups, compared to the young group. More attentions on the ingredient, age and sexuality effect of biomaterial implants should be paid during the clinical practice, especially for the polysaccharide-based materials. This experimental result is of great significance for the selection of biomaterials, particularly the blood contact materials, such as vessel or cardiac device, drug vehicles and hemostatic materials.
研究领域:
生物材料科学
·
免疫学
·
转录组学
·
临床医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 21
·4083-4095
·
IF 7.571
Yajie Pu,Penghui Wang,Rong Yang,Xiaoyan Tan,Tianqi Shi,Juping Ma,Wenliang Xue,Bo Chi
Chronic wounds, especially diabetic wounds, involve abnormally long inflammatory periods due to their pathological microenvironment of high reactive oxygen species (ROS) levels and lack of blood vessels. Here, via a mild, simple and feasible fabrication approach, a sustained oxygenation system is proposed, consisting of MnO2 nanosheets and a dual-network hydrogel fabricated from natural biomaterials including silk fibroin (SF) and carboxymethyl cellulose (CMC). Compared with the initial value (61.09 kPa), the compression modulus of the dual-network hydrogel increased by 116.2% through the coordination of strong covalent bonds and sacrificial coordination bonds constructed by enzymatic crosslinking and UV-irradiation crosslinking; the intrinsic shear-thinning effect endows the dual-network hydrogel with satisfactory injectable properties to be customized as a predetermined shape to accommodate the irregular wounds of diabetes. The encapsulated MnO2 nanosheets can catalyze the excessive ROS into necessary O2in situ and, after co-incubating with the SF/CMC@MnO2 hydrogels, cells in oxidative stress show significantly lower ROS (3 times) and higher O2 (17 times) levels that are conductive to relieving oxidative stress, promoting angiogenesis and reducing inflammation in vivo. Meanwhile, these SF-based hydrogels can offset the overexpression of matrix metalloproteinases (MMPs) in diabetic wounds (more than 80%) and promote remodeling of the extracellular matrix. Eventually, wound healing rates >76% in 7 days and 100% in 14 days were achieved by the bio-fabricated nanocomposite hydrogel and are remarkably faster than the commercial dressing healing rates (<30% in 7 days and <80% in 14 days). These results indicate that this bio-fabricated hydrogel system with multiple and customizable functions has great promise in the personalized clinical care of chronic wounds.
研究领域:
生物材料
·
纳米技术
·
伤口愈合
·
糖尿病
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）