Biomaterials Science
·
2020
·Vol. 8
·期 17
·4810-4820
·
IF 6.183
Yuanyuan Zheng,Weihao Yuan,Huiling Liu,Shaoshan Huang,Liming Bian,Rui Guo
Prolonged inflammatory response and insufficient vascularization cause delayed and poor wound healing. In this study, we fabricated a supramolecular host–guest gelatin (HGM) hydrogel loaded with resveratrol (Res) and histatin-1 (His-1) to suppress inflammation and promote vascularization at skin burn wound sites. The HGM hydrogel showed good properties of shear-thinning and injectability, thereby allowing easy in situ injection and fast adaption to irregular wounds. Res and His-1 were demonstrated to enhance angiogenesis in vitro using cell migration and tube formation assays based on human umbilical vein endothelial cells (HUVECs). In an established rat burn wound model, HGM/Res/His-1 hydrogel treatment promoted wound healing by inhibiting expression of the pro-inflammatory factors of interleukin 6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) and increasing the expression of transforming growth factor β1 (TGF-β1) and platelet endothelial cell adhesion molecule-1 (CD31). HGM/Res/His-1 hydrogel treatment showed comparable efficacy with that of the commercial dressing, Tegaderm™, and therefore shows promising potential for clinical translation.
研究领域:
药剂学
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伤口愈合
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生物材料
·
炎症
·
血管生成
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zili Guo,Tao Chen,Xuehuan Wen,Qiangchang Fu,Jiabin Lai,Jiajin Li,Jiayu Chen,Jie Weng,Wang Wen,Qihua Cao,Junxiong Zhu,Zhaoming Ye,Xiaohua Yu,Lifeng Jiang
Osteoarthritis (OA) pathogenesis is profoundly influenced by dysregulated immune dynamics, where persistent interleukin-17 (IL-17)/T helper 17 (Th17) cell mediated inflammation coordinates with failed regenerative processes to perpetuate joint destruction. Here, we unveil the role of myeloid-derived suppressor cells (MDSCs) as dual-phase regulators that paradoxically orchestrate both inflammatory escalation and tissue repair in OA progression. Intra-articular administration of MDSCs in OA mice amplified IL-17 dependent inflammatory cascades and chemokine-driven leukocyte recruitment, revealing a context-dependent pro-inflammatory phenotype. Unexpectedly, MDSC depletion failed to attenuate joint damage, implying their indispensable yet multifaceted role in OA pathogenesis. Mechanistically, MDSCs exhibited functional plasticity by upregulating arginase-1 to polarize M2 macrophages, fostering a regenerative niche alongside their inflammatory activity. To resolve this duality, we developed a bio-responsive hydrogel-microsphere system integrating transforming growth factor β1 (TGF-β1) and interleukin-1 β1 antibody (anti–IL-1β) loaded mesoporous silica nanoparticles (MSNs). This spatiotemporally controlled platform selectively suppressed MDSC-mediated Th17 cell expansion while harnessing their intrinsic capacity to drive M2 macrophage polarization and chondrogenesis. The resultant shift from a pro-inflammatory to pro-regenerative microenvironment significantly attenuated cartilage erosion and restored joint integrity in OA models. Our findings redefine MDSCs as bifunctional immune orchestrators in OA and establish precision biomaterial guided immune decoding as a paradigm-shifting therapeutic strategy. By engineering MDSC plasticity through antagonistic cytokine delivery, this work provides a blueprint for microenvironment remodeling in degenerative joint diseases.
研究领域:
免疫学
·
再生医学
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生物材料
·
纳米医学
·
风湿病学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Zhang Wenya,He Yuxin,Chu Yun,Zhai Yuanxin,Qian Song,Wang Xinhui,Jiang Pengju,Cui Pengfei,Zhang Yin,Wang Jianhao
The incidence of intrauterine adhesions (IUA) was raised accompanied by the increasing utilization of intrauterine surgery. The postoperative physical barrier methods commonly used, such as balloons and other fillers, have limited effectiveness and may even cause further damage to the remaining endometrial tissue. Herein, we developed an injectable thermosensitive hydrogel using Pluronic F127/F68 as pharmaceutical excipients and curcumin as a natural active molecule. The hydrogel effectively addresses solubility and low bioavailability issues associated with curcumin. In vitro, drug release assays revealed that the amorphous curcumin hydrogel promotes dissolution and sustained release of curcumin. In vitro experiments reveal high biocompatibility of the hydrogel and its ability to enhance vascular formation while inhibiting the expression of fibrotic factor TGF-β1. To assess the effectiveness of preventing intrauterine adhesions, in vivo experiments were conducted using IUA rats and compared with a class III medical device, a new-crosslinked hyaluronic acid gel (NCHA). According to the study, curcumin hydrogel is more effective than the NCHA group in improving the regeneration of the endometrium, increasing the blood supply to the endometrium, and reducing the abnormal deposition of fibrin, thus preventing intrauterine adhesion more effectively. This study provides a promising strategy for treating and preventing IUA.
研究领域:
药剂学
·
生物医学工程
·
妇科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Sun Yage,Zhao Xinrui,Zhang Qian,Yang Rong,Liu Wenguang
The hypoxia microenvironment post myocardial infarction (MI) critically disturbs cellular metabolism and inflammation response, leading to scarce bioenergy supplying, prolonged inflammatory phase and high risk of cardiac fibrosis during cardiac restoration. Herein, an injectable hydrogel is prepared by Schiff-base reaction between fructose-1,6-bisphosphate (FBP)-grafted carboxymethyl chitosan (CF) and oxidized dextran (OD), following by loading fucoidan-coated baicalin (BA)-encapsulated zein nanoparticles (BFZ NPs), in which immunoregulatory and metabolism improving functions are integrally included. The grafted FBP serves to enhance glycolysis and provide more bioenergy for cardiomyocytes survival under hypoxia microenvironment, and elevating cellular antioxidant capacity via pentose phosphate pathway. OD with intrinsic anti-inflammatory effect can induce M2 polarization of macrophages to accelerate inflammatory elimination. While facing the possibility of endothelial-to-mesenchymal transition (EndoMT) caused by excessive expressed TGF-β1 secreted from M2 macrophages, BFZ NPs can target endothelia cells and intracellularly release BA to regulate the level of fatty acid oxidation, resulting in retained endothelial features and decreased risk of cardiac fibrosis. After being injecting the hydrogel into rats’ infarcted cardiac, the 28 day-post surgical outcomes demonstrate its benign effects on restoring cardiac functions and attenuating adverse left ventricular remodeling. This study shows a promising measure for MI treatment with immunoregulating and metabolism regulation comprehensively.
研究领域:
生物医学工程
·
心脏病学
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jun Zhang,Lei Su,Zhinan Liu,Jincheng Tang,Lichen Zhang,Ziang Li,Dong Zhou,Zhuo Sun,Kun Xi,Peirong Lu,Guohua Deng
Following an ocular chemical injury, the release of neutrophil extracellular traps (NETs) triggers an innate immune cascade fibrotic effect involving macrophages (Mø), which limits corneal repair. However, the interplay and mechanisms between NETs and macrophages, as well as the coordination between the innate immunity and corneal repair, remain challenging issues. Using a co-culture system, we report that chemical stimulation exacerbates the accumulation of reactive oxygen species (ROS) within the polymorphonuclear neutrophils, leading to NET formation and the activation of M2 macrophages, ultimately inducing pathological fibrosis of the ocular surface through the IL-10/STAT3/TGF-β1/Smad2 axis. Inspired by the locally formed acidic microenvironment mediated by innate acute inflammatory stimulation, we further integrate sericin with oxidized chitosan nanoparticles loaded with black phosphorus quantum dots (BPQDs) using Schiff base chemistry to construct a functional pH-responsive hydrogel. Following corneal injury , the hydrogel selectively releases BPQDs in response to the acidic environment, inhibiting the innate immune cascade fibrosis triggered by the PMN-ROS-NETs. Thus, corneal pathological fibrosis is alleviated and reshaping of the ocular surface takes place. These results represent a refinement of the mechanism of inherent immune effector cell interactions, and provide new research ideas for the construction of nano biomaterials that regulate pathological fibrosis.
研究领域:
生物材料
·
免疫学
·
眼科
·
组织工程
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Lina Ba,Mingyao E,Ruixuan Wang,Nan Wu,Rui Wang,Renling Liu,Xiang Feng,Hanping Qi,Hongli Sun,Guofen Qiao
Background Cardiac remodeling is a common pathological feature in many cardiac diseases, characterized by cardiac hypertrophy and fibrosis. Triptolide (TP) is a natural compound derived from Tripterygium wilfordii Hook F. However, the related mechanism of it in cardiac remodeling has not been fully understood. Methods and results Transverse aortic constriction (TAC)-induced cardiac hypertrophic mouse model and angiotensin II (Ang II)-induced cardiomyocytes hypertrophic model were performed. Firstly, the results indicate that TP can improve cardiac function, decreased cardiomyocyte surface area and fibrosis area, as well as lowered the protein expressions of brain natriuretic peptide (BNP), β-major histocompatibility complex (β-MHC), type I and III collagen (Col I and III). Secondly, TP suppressed cardiac pyroptosis, and decreased the levels of Interleukin-1β (IL-1β), Interleukin-18 (IL-18) by Enzyme-linked immunosorbent assay (ELISA), and pyroptosis-associated proteins. Furthermore, TP enhanced the expressions of Nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). Interestingly, when Nrf2 was silenced by siRNA, TP lost its properties of reducing pyroptosis and cardiac hypertrophy. In addition, in the Transforming Growth Factor β1 (TGF-β1)-induced primary human coronary artery endothelial cells (HCAEC) model, TP was found to inhibit the process of endothelial-to-mesenchymal transition (EndMT), characterized by the loss of endothelial-specific markers and the gain of mesenchymal markers. This was accompanied by a suppression of Slug, Snail, and Twist expression. Meanwhile, the inhibitory effect of TP on EndMT was weakened when Nrf2 was silenced by siRNA. Lastly, potential targets of TP were identified through network pharmacology analysis, and found that Ubiquitin-Specific Protease 14 (USP14) was one of them. Simultaneously, the data indicated that decrease the upregulation of USP14 and Kelch-like ECH-Associated Protein 1 (Keap1) caused by cardiac remodeling. However, Keap1 was decreased and Nrf2 was increased when USP14 was silenced. Furthermore, CoIP analysis showed that USP14 directly interacts with Keap1. Conclusion TP can observably reduce pyroptosis and EndMT by targeting the USP14/Keap1/Nrf2 pathway, thereby significantly attenuating cardiac remodeling.
研究领域:
心脏病学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Yan Chen,Ming Zhang,Zhifang Liu,Ning Zhang,Qingpeng Wang
Tumor microenvironment (TME) is a pivotal factor driving the tumor metastasis and leading to the failure of tumor therapy. Here, a series of ursodeoxycholic acid platinum(IV) conjugates with potency in remodeling the TME through suppressing JAK2/STAT3 signaling was developed. A candidate was screened out, which displayed potent antiproliferative and antimetastatic performance both in vitro and in vivo. It displayed superior pharmacokinetic properties compared to cisplatin. Serious DNA injury was induced, and then mitochondria-mediated apoptosis was initiated through the Bcl-2/Bax/Caspase3 pathway. The JAK2/STAT3 and TGF-β1 signaling pathways were remarkably inhibited, and pro-death autophagy was subsequently promoted. The inflammatory and hypoxic TME was suppressed by downregulating COX-2, MMP9, and HIF-1α, which resulted in inhibited angiogenesis in tumors by inhibiting the HIF-1α/VEGFA axis. Additionally, the immunosuppressive TME was reversed by blocking the immune checkpoint PD-L1, further improving the density of CD3+ and CD8+ tumor-infiltrating lymphocytes, and promoting macrophage polarization from M2- to M1-type.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）