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ACS Applied Materials & Interfaces · 2022 · IF 10.383

Superelastic, Breathable, and High-Barrier Nanofibrous Membranes with Biomimetic ECM Structure for Toxic Chemical Protection

Nankai Song,Xuan Zhang,Yang Si,Jianyong Yu,Bin Ding

As the last line of protection for humans, chemical protective suits provided safe and effective protection where chemical warfare agents (CWAs) or chemical reagents leaked; however, the existing chemical protective clothing had poor wearing pressure comfort due to the limitation of inherent materials. Herein, we reported a scalable strategy to fabricate chemical protective fabric (CPF) with a biomimetic extracellular matrix (ECM) barrier layer composed of an elastic fiber framework based on the cross-linked nanofiber membrane and the styrene–butadiene–styrene block copolymer (SBS)/acticarbon matrix. The construction of the reliable and strategical biomimetic ECM structure succeeded in fulfilling hazardous chemical barrier properties, recoverable deformation, and thermal comfort improvement. The resulting CPF exhibited waterproofness with exceeding 200 kPa hydrostatic pressure and exceptional WVT of 550.96 g m–2 d–1, rapid elastic recovery from a strain of 80%, high-cycle fatigue resistance, superior barrier performance against toxic chemicals, and keeping CEES resistance after 100 tensile loading cycles. The successful preparation of the fascinating biomimetic nanofibrous membrane may provide a particular research foundation for developing chemical protective clothing in the future.

研究领域: 材料科学 · 生物医学工程 · 化学防护领域
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

ECM-mimetic glucomannan hydrogel promotes pressure ulcer healing by scavenging ROS, promoting angiogenesis and regulating macrophages

Mingming Sun,Qiuying Wang,Ting Li,Wenzhu Wang,Zihan Li,Yufei Ji,Shuangyue Zhang,Yan Li,Wenshuai Liu,Yan Yu

Pressure ulcers (PUs) have emerged as a significant burden on both individuals and society. Effective treatment of PUs is a significant clinical challenge due to the compromised tissue microenvironment characterized by extracellular matrix (ECM) depletion, increased levels of reactive oxygen species (ROS), excessive inflammation and impaired angiogenesis. To this end, we have developed a glucomannan hydrogel (GM-P gel ) that mimics the skin's extracellular matrix to accelerate wound healing by regulating chronic inflammation in the PUs. This hydrogel not only faithfully replicates the components and nanofibrous architecture of ECM-like glycoproteins but also exhibits remarkable capabilities in enhancing neovascularization, scavenging ROS, and promoting macrophage polarization toward the M2 phenotype. In summary, this ECM-mimetic multifunctional hydrogel emerges as a promising dressing with diverse functionalities, capable of reshaping the compromised tissue environment without the need for additional drugs, exogenous cytokines, or cells. This presents a compelling and effective strategy for the repair and regeneration of chronic cutaneous wounds.

CAS / MDL: 573-58-0 7790-28-5
研究领域: 伤口愈合 · 组织工程 · 生物材料 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nano Today · 2022 · IF 18.962

ECM-inspired peptide dendrimer microgels with human MSCs encapsulation for systemic lupus erythematosus treatment

Haofang Zhu,Bin Kong,Min Nie,Cheng Zhao,Rui Liu,Ying Xie,Yuanjin Zhao,Lingyun Sun

Mesenchymal stem cells (MSCs) transplantation is an emerging and attractive therapy for immune dysregulation diseases like systemic lupus erythematosus (SLE). However, its application is hindered by short in vivo persistence and poor cellular survival after injection. Here, inspired by the native extracellular matrix (ECM) composition , we presented a novel peptide dendrimer-based microgel encapsulated with MSCs via a microfluidic approach for SLE treatment. By varying microfluidic parameters, monodisperse microgels with tunable diameters, porous microstructures, mechanical stiffness, and immune-isolation potential could be precisely achieved. As the water polymerization environment and ECM like components, the resultant microgels exhibited minimal toxicity in vivo and in vitro. We have also demonstrated that the MSCs encapsulated microgels could significantly increase the cellular bioactivity , enhance the immunomodulatory function, and attenuate disease symptoms in MRL/lpr mice. These results indicate the bioinspired microgels with MSCs encapsulation have potential clinical values in the treatment of SLE and other immune dysregulation diseases.

研究领域: 生物材料 · 干细胞治疗 · 免疫学 · 生物医学工程
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BIOMATERIALS · 2017 · IF 8.402

In situ sequestration of endogenous PDGF-BB with an ECM-mimetic sponge for accelerated wound healing

Qiu Li,Yiming Niu,Huajia Diao,Lintao Wang,Xiuping Chen,Yitao Wang,Lei Dong,Chunming Wang

Recapitulating the typical features of extracellular matrix (ECM) in engineered biomaterials is crucial for preparing a suitable niche to activate endogenous tissue repair. Here, we report the design and evaluation of an ECM-mimetic scaffold that successfully accelerated wound healing through enriching endogenous platelet-derived growth factor-BB (PDGF-BB). Specifically, we prepared a electrospun hydrogel sponge (EGS) comprising a PDGF-BB-binding polysaccharide (EUP3) and gelatin. The two polymers in concert exerted a ‘retention-and-release’ function: upon the application of EGS in vivo , EUP3 started to bind and sequester endogenous PDGF-BB at the wound site; gradually, gelatin was degraded to free the PDGF-BB/EUP3 complex that acted on the cells in situ . Our serial in vitro and in vivo tests validated the efficacy of EGS in retaining PDGF-BB, releasing PDGF-BB/EUP3 in response to collagenase, and promoting various PDGF-BB-mediated regenerative activities. Particularly, EGS accelerated the repair of a full-thickness skin wound in mice and induced optimal neo-tissue formation, without the addition of any exogenous GFs, cells or genes. Collectively, our results suggest that, by mimicking the distinctive GF-affinitive feature of ECM, EGS as an engineered biomaterial can effectively harness the endogenous regenerative power of the native tissue. Our investigation may inspire the design of new, effective and safer approaches for tissue regeneration.

CAS / MDL: 75-89-8
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 伤口愈合
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ACS Applied Materials & Interfaces · 2017 · IF 7.504

Surface Modification with ECM-Inspired SDF-1α/Laminin-Loaded Nanocoating for Vascular Wound Healing

Tao Liu,Xin Wang,Xiaohan Tang,Tao Gong,Wei Ye,Changjiang Pan,Hongyan Ding,Xun Luo,Xia Li,Qing Mei Wang

Surface biomimetic modification with extra-cellular matrix (ECM)-derived biomolecules is an emerging potential method of accelerating the healing of vascular stent lesions. However, insufficient capacity of the constructed biofunctional layer in maintaining its long-term efficiency and preventing thrombus and neointimal hyperplasia continue to be major limitations in clinical application. On the basis of the structure and function of ECM, in this study, we constructed a novel stromal cell-derived factor-1α (SDF-1α)/laminin-loaded nanocoating on the 316L stainless steel (SS) surface to provide improved function in modulation of vascular remodeling. The modified surface was found to control delivery of biomolecules and exhibit promising potential to provide stage-adjusted treatment after injury. An in vitro biocompatibility study suggested that the constructed layer may effectively prevent thrombosis formation by inhibiting platelet adhesion and activation, while accelerating endothelium regeneration by inducing endothelial cell (EC) migration and endothelial progenitor cell (EPC) aggregation. An in vivo animal test further demonstrated that the nanocoating may prevent thrombus and neointimal hyperplasia after implantation for 3 months. Therefore, the ECM-inspired nanocoating described in this study is a promising novel approach for vascular stent surface modification.

CAS / MDL: 9041-08-1
研究领域: 生物材料 · 组织工程 · 血管生物学 · 纳米技术 · 生物医学工程
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Bioactive Materials · 2024 · IF 18

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration

Hao Zhou,Jinpeng He,Renfeng Liu,Jun Cheng,Yuhao Yuan,Wanpu Mao,Jun Zhou,Honghui He,Qianqi Liu,Wei Tan,Cijun Shuai,Youwen Deng

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

研究领域: 生物医学工程 · 组织工程 · 骨科 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2023 · IF 9.7

ECM-engineered electrospun fibers with an immune cascade effect for inhibiting tissue fibrosis

Ming Qian,Shun Li,Kun Xi,Jincheng Tang,Xiaofeng Shen,Yong Liu,Ran Guo,Nannan Zhang,Yong Gu,Yun Xu,Wenguo Cui,Liang Chen

Tissue regeneration/fibrosis after injury is intricately regulated by the immune cascade reaction and extracellular matrix (ECM). Dysregulated cascade signal could jeopardize tissue homeostasis leading to fibrosis. Bioactive scaffolds mimicking natural ECM microstructure and chemistry could regulate the cascade reaction to achieve tissue regeneration. The current study constructed an ECM-engineered micro/nanofibrous scaffold using self-assembled nanofibrous collagen and decorin (DCN)-loaded microfibers to regulate the immune cascade reaction. The ECM-engineered scaffold promoted anti-inflammatory and pro-regenerative effects, M2 polarization of macrophages, by nanofibrous collagen. The ECM-engineered scaffold could release DCN to inhibit inflammation-associated fibrous angiogenesis. Yet, to prevent excessive M2 activity leading to tissue fibrosis, controlled release of DCN was expected to elicit M1 activity and achieve M1/M2 balance in the repair process. Regulated cascade reaction guided favorable crosstalk between macrophages, endothelial cells and fibroblasts by proximity. Additionally, decorin could also antagonize TGF-β1 via TGF-β/Smad3 pathway to suppress fibrotic activity of fibroblasts. Hence, ECM-engineered scaffolds could exert effective regulation of the immune cascade reaction by microstructure and DCN release and achieve the balance between tissue fibrosis and regeneration. Statement of Significance With the incidence of up to 74.6%, failed back surgery syndrome (FBSS) has been a lingering issue in spine surgery, which poses a heavy socio-economic burden to society. Epidural fibrosis is believed to be responsible for the onset of FBSS. Current biomaterial-based strategies treating epidural fibrosis mainly rely on physical barriers and unidirectional suppression of inflammation. Regulation of the immune cascade reaction for inhibiting fibrosis has not been widely studied. Based on the simultaneous regulation of M1/M2 polarization and intercellular crosstalk, the ECM-engineered micro/nanofibrous scaffolds constructed in the current study could exert an immune cascade effect to coordinate tissue regeneration and inhibit fibrosis. This finding makes a significant contribution in the development of a treatment for epidural fibrosis and FBSS.

研究领域: 组织工程 · 再生医学 · 免疫学 · 生物材料 · 脊柱外科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COMPOSITES PART B-ENGINEERING · 2024 · IF 12.7

Dynamically crosslinked ECM-like hydrogels loaded with ROS-responsive drug nanoparticles for treating inflammation in myocardial infarction and stroke

Zhicun Wang,Cheng Hu,Wen Zhang,Wenqi Liu,Shuyi He,Yang Liu,Li Yang,Yunbing Wang

Following a myocardial infarction (MI) or stroke, the excessive generation of reactive oxygen species (ROS) within a brief timeframe may induce a pronounced inflammatory reaction, which exacerbates the progression of the disease. Thus, there is an urgent need to design a biomaterial to inhibit the inflammatory response associated with MI and stroke. In this study, we designed a reversible extracellular matrix (ECM)-like hydrogel via borate ester crosslinking, which responds to the inflammatory microenvironment affected by MI and stroke. At the same time, we developed a new type of loaded polymer nanoparticle (TK-DA) that can respond to ROS in ischemic regions and release the anti-inflammatory drug dexamethasone. Ultimately, we integrated the nanoparticles and ECM-like hydrogel to fabricate a functional hydrogel. To verify the therapeutic effect of the functional hydrogel, we established two models of typical ischemic diseases, MI and stroke. The results showed that the hydrogel substantially reduced ROS levels and inflammation in vitro. Moreover, the results of the two in vivo animal models demonstrated that this functional hydrogel can effectively treat MI and stroke by suppressing inflammatory responses, mitigating apoptosis, and promoting neovascularization. In conclusion, the functional hydrogel strategy presents a universally applicable treatment approach for ischemic cardiovascular and cerebrovascular diseases, which are not limited solely to the treatment of MI and stroke, but also hold future potential for clinical applications.

研究领域: 生物医学工程 · 药学 · 心血管疾病 · 神经科学
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Advanced Healthcare Materials · 2022 ·Vol. 12 ·期 1 ·2201594 · IF 11.092

An ECM-Mimicking, Injectable, Viscoelastic Hydrogel for Treatment of Brain Lesions

Yan Hu,Yuanbo Jia,Siwei Wang,Yufei Ma,Guoyou Huang,Tan Ding,Dayun Feng,Guy M. Genin,Zhao Wei,Feng Xu

Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. It is hypothesized that these challenges arise in part from the mismatch of composition, stiffness, and viscoelasticity between the hydrogel and the brain parenchyma, and this hypothesis is tested by developing and evaluating a self-healing hydrogel that not only mimics the composition, but also the stiffness and viscoelasticity of native brain parenchyma. The hydrogel is crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA-PBA) and dopamine grafted gelatin (Gel-Dopa). This HA-PBA/Gel-Dopa hydrogel could be injected into a lesion cavity in a shear-thinning manner with rapid hemostasis, high tissue adhesion, and efficient self-healing. In an in vivo mouse model of brain lesions, the multi-functional injectable hydrogel is found to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for extracellular matrix-mimicking viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses toward potential application in humans.

研究领域: 神经科学 · 材料科学 · 生物材料 · 组织工程
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Biomaterials Science · 2021 ·Vol. 9 ·期 23 ·7895-7910 · IF 6.843

Exploring the match between the degradation of the ECM-based composites and tissue remodeling in a full-thickness abdominal wall defect model

Guangxiu Cao,Wei He,Yubo Fan,Xiaoming Li

The repair of abdominal wall defects is currently a clinical challenge. A naturally derived extracellular matrix (ECM) such as small intestine submucosa (SIS) has received great attention in abdominal wall defect repair because of its remarkable bioactivity, biodegradability and tissue regeneration. The match between material degradation and tissue remodeling is very important for the realization of ideal repair effectiveness. In this study, a near-infrared (NIR) fluorescent dye Cy5.5 NHS ester was used to label ECM-based (ECMB) composites consisting of SIS and chitosan/elastin electrospun nanofibers for monitoring material degradation. The tissue remodeling in the ECMB composites for a full-thickness abdominal wall defect repair was systematically investigated by a series of tests including wall thickness measurement, muscle regeneration analysis and angiogenesis assessment. The main findings were: (1) real-time and noninvasive degradation monitoring of the ECMB composites until complete degradation could be realized by chemical conjugation with a Cy5.5 NHS ester. (2) In a full-thickness abdominal wall defect model, the explant thickness could be used as an intuitional indicator for evaluating the tissue remodeling efficiency in the ECMB composites, and the accuracy of this indicator was verified by various examinations including collagen deposition, angiogenesis, and muscle regeneration. The present study could provide new insight into evaluating tissue repair effectiveness of the ECMB composites.

CAS / MDL: 9012-76-4
研究领域: 生物医学工程 · 组织工程 · 再生医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Medical Molecular Morphology · 2021 ·Vol. 54 ·期 4 ·337-345 · IF 2.309

LncRNA PICSAR binds to miR-485-5p and activates TGF-β1/Smad to promote abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and excessive deposition of extracellular matrix (ECM)

Xu Sijia,Dong Wenxin,Shi Yu

The purpose of this study is to explore whether LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, influencing the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation. PICSAR and miR-485-5p expressions were detected by qPCR. Cell proliferation was examined by CCK-8. Protein expressions were determined by western blot. Immunofluorescence detected the Ki-67 expression. Dual-luciferase followed by immunoprecipitation was performed to verify the interaction between PICSAR and miR-485-5p. Interference with PICSAR inhibited the abnormal proliferation of hypertrophic scar fibroblasts (HSFs) and the excessive deposition of ECM. It was also confirmed in our study that MiR-485-5p is a direct target of PICSAR in HSFs. Additionally, inhibition of miR-485-5p reversed the effect of PICSAR knockdown in HSFs. LncRNA PICSAR binds to miR-485-5p and thereby activates TGF-β1/Smad signaling pathway, promoting the abnormal proliferation of fibroblasts and excessive deposition of ECM in hypertrophic scar formation.

CAS / MDL: 9048-46-8 30525-89-4
研究领域: 分子生物学 · 细胞生物学 · 伤口愈合
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Cell Reports · 2023 · IF 8.8

Mechanotransduction in response to ECM stiffening impairs cGAS immune signaling in tumor cells

Yingqi Liu,Xuemei Yao,Youbo Zhao,De Fang,Lei Shi,Li Yang,Guanbin Song,Kaiyong Cai,Liqi Li,Qin Deng,Menghuan Li,Zhong Luo

The tumor microenvironment (TME) plays decisive roles in disabling T cell-mediated antitumor immunity, but the immunoregulatory functions of its biophysical properties remain elusive. Extracellular matrix (ECM) stiffening is a hallmark of solid tumors. Here, we report that the stiffened ECM contributes to the immunosuppression in TME via activating the Rho-associated coiled-coil-containing protein kinase (ROCK)-myosin IIA-filamentous actin (F-actin) mechanosignaling pathway in tumor cells to promote the generation of TRIM14-scavenging nonmuscle myosin heavy chain IIA (NMHC-IIA)-F-actin stress fibers, thus accelerating the autophagic degradation of cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) to deprive tumor cyclic GMP-AMP (cGAMP) and further attenuating tumor immunogenicity. Pharmacological inhibition of myosin IIA effector molecules with blebbistatin (BLEB) or the RhoA upstream regulator of this pathway with simvastatin (SIM) restored tumor-intrinsic cGAS-mediated cGAMP production and enhanced antitumor immunity. Our work identifies that ECM stiffness is an important biophysical cue to regulate tumor immunogenicity via the ROCK-myosin IIA-F-actin axis and that inhibiting this mechanosignaling pathway could boost immunotherapeutic efficacy for effective solid tumor treatment.

研究领域: 癌症生物学 · 免疫学 · 细胞生物学 · 生物物理学
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