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过度炎症
Matter · 2022 · IF 19.967

A natural extracellular matrix hydrogel through selective nutrient restriction for hyperinflammatory starvation therapy

Pengfei Chen,Kaifeng Pan,Nan Song,Yang Yang,Chenhui Gu,Peiyu Zhong,Lin Li,Mobai Li,Ying Zhang,Zhanqiu Dai,Liqing Shangguan,Chenyang Lei,Zhaoming Liu,Jianfeng Zhang,Ruikang Tang,Chao Liu,Shunwu Fan,Xianfeng Lin

An adequate nutrient supply is essential for maintaining the function of highly active immune cells; however, in an environment of excessive inflammation, this nutrient supply aggravates inflammation. We propose a “hyperinflammatory starvation therapy” for various diseases caused by excessive metabolism by highly selective restriction of the supply of local nutrients. Here we developed a natural, physiologically triggered, injectable, nano-platelet vesicle-based extracellular matrix hydrogel (NPV-ECM). As a proof of concept, in representative excessive inflammatory disease diabetic wounds, we demonstrated that the NPV-ECM can selectively regulate nutrient transportation based on intermolecular interactions, remodel the local immune microenvironment, limit the state of excess metabolism, promote angiogenesis, and achieve wound healing. Moving into the clinic, we conducted a clinical trial in patients with diabetic foot ulcers to verify the safety and therapeutic effect of the NPV-ECM. This study provides an understanding of the preparation and application of natural ECM biomaterials for hyperinflammatory starvation therapy.

CAS / MDL: 38183-12-9
研究领域: 生物材料 · 免疫学 · 组织工程 · 转化医学 · 代谢调控 · 创伤修复 · 纳米医学
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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-16 · IF 17.694

Reactive metal boride nanoparticles trap lipopolysaccharide and peptidoglycan for bacteria-infected wound healing

Meng Yun,Chen Lijie,Chen Yang,Shi Jieyun,Zhang Zheng,Wang Yiwen,Wu Fan,Jiang Xingwu,Yang Wei,Zhang Li,Wang Chaochao,Meng Xianfu,Wu Yelin,Bu Wenbo

Bacteria and excessive inflammation are two main factors causing non-healing wounds. However, current studies have mainly focused on the inhibition of bacteria survival for wound healing while ignoring the excessive inflammation induced by dead bacteria-released lipopolysaccharide (LPS) or peptidoglycan (PGN). Herein, a boron-trapping strategy has been proposed to prevent both infection and excessive inflammation by synthesizing a class of reactive metal boride nanoparticles (MB NPs). Our results show that the MB NPs are gradually hydrolyzed to generate boron dihydroxy groups and metal cations while generating a local alkaline microenvironment. This microenvironment greatly enhances boron dihydroxy groups to trap LPS or PGN through an esterification reaction, which not only enhances metal cation-induced bacterial death but also inhibits dead bacteria-induced excessive inflammation both in vitro and in vivo, finally accelerating wound healing. Taken together, this boron-trapping strategy provides an approach to the treatment of bacterial infection and the accompanying inflammation.

研究领域: 纳米技术 · 生物医学工程 · 伤口愈合 · 炎症 · 细菌感染
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Advanced Healthcare Materials · 2024 · IF 10

Photothermal Iron-Based Riboflavin Microneedles for the Treatment of Bacterial Keratitis via Ion Therapy and Immunomodulation

Jun Zhou,Lisha Zhang,Yaqi Wei,Qiang Wu,Kaibo Mao,Xiaoli Wang,Jinfeng Cai,Xia Li,Yongxiang Jiang

Bacterial biofilm formation protects bacteria from antibiotics and the immune system, excessive inflammation further complicates treatment. Here, iron-based metal–organic framework (MIL-101)-loaded riboflavin nanoparticles are designed for the therapeutic challenge of biofilm infection and hyperinflammation in bacterial keratitis. Specifically, MIL-101 produces a thermal effect under exogenous near-infrared light irradiation, which synergizes with ferroptosis-like bacterial death induced by iron ions to exert an effective biofilm infection eradication effect. On the other hand, the disintegration of MIL-101 sustains the release of riboflavin, which inhibits the pro-inflammatory response of macrophage over-activation by modulating their phenotypic switch. In addition, to solve the problems of short residence time, poor permeability, and low bioavailability of corneal medication, the MR@MN microneedle patch is further prepared by loading nanoparticles into SilMA hydrogel, which ultimately achieves painless, transepithelial, and highly efficient drug delivery. In vivo and ex vivo experiments demonstrate the effectiveness of this approach in eliminating bacterial infection and promoting corneal healing. Therefore, the MRMN patch, acting as an ocular drug delivery system with the ability of rapid corneal healing, promises a cost-effective solution for the treatment of bacterial keratitis, which may also lead to a new approach for treating bacterial keratitis in clinics.

研究领域: 眼科学 · 药学 · 生物医学工程 · 免疫学 · 材料科学
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Advanced Healthcare Materials · 2024 · IF 10

An Immune-Regulating Polysaccharide Hybrid Hydrogel with Mild Photothermal Effect and Anti-Inflammatory for Accelerating Infected Wound Healing

ShengZhe Zhou,Xueliang Zhang,Wei Ni,Yu He,Ming Li,Caixia Wang,Yubing Bai,Hao Zhang,Min Yao

Bacterial infections and excessive inflammation present substantial challenges for clinical wound healing. Hydrogels with mild photothermal (PTT) effects have emerged as promising agents owing to their dual actions: positive effects on cells and negative effects on bacteria. Here, an injectable self-healing hydrogel of oxidized konjac glucomannan/arginine-modified chitosan (OKGM/CS-Arg, OC) integrated with protocatechualdehyde-@Fe (PF) nanoparticles capable of effectively absorbing near-infrared radiation is synthesized successfully. The OC/PF hydrogels exhibit excellent mechanical properties, biocompatibility, and antioxidant activity. Moreover, in synergy with PTT, OC/PF demonstrates potent antibacterial effects while concurrently stimulating cell migration and new blood vessel formation. In methicillin-resistant Staphylococcus aureus -infected full-thickness mouse wounds, the OC/PF hydrogel displays remarkable antibacterial and anti-inflammatory activities, and accelerates wound healing by regulating the wound immune microenvironment and promoting M2 macrophage polarization. Consequently, the OC/PF hydrogel represents a novel therapeutic approach for treating multidrug-resistant bacterial infections and offers a technologically advanced solution for managing infectious wounds in clinical settings.

研究领域: 生物医学工程 · 材料科学 · 纳米技术 · 伤口愈合 · 传染病学 · 免疫学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

A bioinspired regenerative antimicrobial hydrogel coating for cardiovascular implantable electronic devices

Xudong Yao,Miner Hu,Xinrang Zhai,Junxin Lin,Xiaojun Xia,Wei Wei,Shudong Xia

Elderly patients predispose to cardiovascular implantable electronic devices (CIEDs) pocket infections due to multiple comorbidities. Treating infections with the antibiotics further carry higher risks for complications, and surgical intervention can be costly when device removal and reimplantation are required, both emphasizing the importance of novel preventive strategies to minimize the incidence of pocket infections. To meet the unique needs for elderly, we constructed an CIED surface modified hydrogel which crosslinked polyethylene glycol diacrylate (PEGDA) with hyaluronic acid-nitrobenzene (HN) to form the polymeric structures that mimic the natural environment for promoting “Pocket” surrounding tissue integration and healing. Importantly, we synthesized the new peptidomimetics FK-13 derived by shortening amino acid sequence of LL-37 which is the only human cathelicidin-derived antimicrobial peptide. By incorporating FK-13 with initial PN hydrogel via Schiff base formation, the created PN-FK hydrogel exhibited broad-spectrum antimicrobial activity   against bacteria with excellent biocompatibility and mechanical properties in a long-term release manner. In an in vitro setting, PN-FK hydrogel demonstrated the regeneration capacity by expression of Hmox1, Col5 and Col6 associated genes in fibroblasts as well as expression of Gpx1, Cdc20 and MMP9 genes in stem cells to accelerate self-renewal, collagen secretion and reconstitution of matrix components. In the following in vivo model of subcutaneous implantation, CIED-shape titanium mesh with surface modification by PN-FK hydrogel efficiently subsided over-inflammation compared to bare titanium implant, and expedited collagen deposition and angiogenesis in peri -pocket tissues within 2 weeks. These findings underscore the potential of the PN-FK hydrogel as a transformative approach to CIED postoperative management, offering a dual-action solution that combines infection resistance with tissue regeneration capabilities.

研究领域: 生物医学工程 · 材料科学 · 生物材料 · 组织工程 · 抗菌技术 · 心脏病学 · 老年医学
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