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Histone lactylation regulates autophagy of hyperplastic scar fibroblasts by inhibiting the transcriptional activity of phosphatase and tensin homologue. 组蛋白乳酰化通过抑制磷酸酶和天丝同源物的转录活性调节增生瘢痕成纤维细胞的自噬。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-05-19 DOI: 10.1111/wrr.13188
Xiaosong Liu, Biao Wang

Hyperplastic scar (HS) is an overreaction of tissue to skin injury caused by local fibroblast proliferation and excessive collagen production. Histone posttranslational modification patterns are important epigenetic processes that control various biological activities. This study was designed to investigate the effects of histone lactylation on HS and the underlying mechanism. Western blot was used to analyse the lactylation level in HS patients and fibroblasts (HSFs). In vitro experiments, western blot, cell counting kit-8, and immunofluorescence staining were performed to detect the collagen level, cell viability, and autophagy, respectively. The relationship between snai2 (SLUG) and phosphatase and tensin homologue (PTEN) was assessed by RNA immunoprecipitation and dual-luciferase reporter assays. The results showed that the histone lactylation level was upregulated in HS tissues and HSFs. HSFs showed increased collagen production and cell viability, and decreased autophagy. Silencing of lactate dehydrogenase A (LDHA) promoted the transcription of PTEN by inhibiting SLUG, thus promoting autophagy. Knockdown of LDHA inhibited collagen deposition and cell viability, and increased autophagy in HSFs, and the results were reversed after PTEN inhibition. In summary, histone lactylation inhibited the transcription activity of PTEN by promoting SLUG, thereby suppressing autophagy and promoting collagen deposition and cell viability of HSFs, which might provide effective therapeutic strategies in HS.

增生性疤痕(HS)是由于局部成纤维细胞增殖和胶原蛋白过度增生造成的皮肤损伤后组织的过度反应。组蛋白翻译后修饰模式是控制各种生物活动的重要表观遗传过程。本研究旨在探讨组蛋白乳酰化对 HS 的影响及其内在机制。研究采用Western印迹法分析HS患者和成纤维细胞(HSFs)的乳酸化水平。在体外实验中,通过 Western 印迹、细胞计数试剂盒-8 和免疫荧光染色分别检测胶原蛋白水平、细胞活力和自噬。通过RNA免疫沉淀和双荧光素酶报告实验评估了snai2(SLUG)与磷酸酶和天丝同源物(PTEN)之间的关系。结果显示,组蛋白乳化水平在 HS 组织和 HSFs 中上调。HSFs 的胶原蛋白生成和细胞活力增加,自噬功能降低。沉默乳酸脱氢酶A(LDHA)可通过抑制SLUG促进PTEN的转录,从而促进自噬。在 HSFs 中,敲除 LDHA 可抑制胶原沉积和细胞活力,增加自噬,而在抑制 PTEN 后结果逆转。综上所述,组蛋白乳酰化通过促进SLUG抑制了PTEN的转录活性,从而抑制了HSFs的自噬,促进了胶原沉积和细胞活力,这可能会为HS提供有效的治疗策略。
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引用次数: 0
Performance of artificial intelligence chatbots in interpreting clinical images of pressure injuries. 人工智能聊天机器人在解读压力损伤临床图像中的表现。
IF 2.9 3区 医学 Q1 Medicine Pub Date : 2024-05-15 DOI: 10.1111/wrr.13189
Makoto Shiraishi, Koji Kanayama, Daichi Kurita, Yuta Moriwaki, Mutsumi Okazaki

To evaluate the accuracy of AI chatbots in staging pressure injuries according to the National Pressure Injury Advisory Panel (NPIAP) Staging through clinical image interpretation, a cross-sectional design was conducted to assess five leading publicly available AI chatbots. As a result, three chatbots were unable to interpret the clinical images, whereas GPT-4 Turbo achieved a high accuracy rate (83.0%) in staging pressure injuries, notably outperforming BingAI Creative mode (24.0%) with statistical significance (p < 0.001). GPT-4 Turbo accurately identified Stages 1 (p < 0.001), 3 (p = 0.001), and 4 (p < 0.001) pressure injuries, and suspected deep tissue injuries (p < 0.001), while BingAI demonstrated significantly lower accuracy across all stages. The findings highlight the potential of AI chatbots, especially GPT-4 Turbo, in accurately diagnosing images and aiding the subsequent management of pressure injuries.

为了评估人工智能聊天机器人根据国家压力伤害顾问团(NPIAP)通过临床图像判读进行压力伤害分期的准确性,我们采用横断面设计评估了五款领先的公开人工智能聊天机器人。结果发现,有三个聊天机器人无法解读临床图像,而 GPT-4 Turbo 在压力损伤分期方面达到了很高的准确率(83.0%),明显优于 BingAI Creative 模式(24.0%),且具有统计学意义(p<0.05)。
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引用次数: 0
The proliferative effects of stem cells from apical papilla-conditioned medium on rat corneal endothelial cells. 顶端乳头调节培养基中的干细胞对大鼠角膜内皮细胞的增殖作用。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-02-28 DOI: 10.1111/wrr.13161
Kimia Rahimiyan, Mohammad Hossein Nasr Esfahani, Fereshteh Karamali

The cornea, positioned at the forefront of the eye, refracts the light for focusing images on the retina. Damage to this transparent structure can lead to various visual disorders. The corneal endothelial cells (CECs) are crucial for transparency and homeostasis, but lack the ability to reproduce. Significant damage results in structure destruction and vision impairment. While extensive research has aimed at the restoring the corneal endothelial layer, including endothelial proliferation for functional monolayers remains challenging. Our previous studies confirmed the proliferative activity of stem cells from apical papilla-conditioned medium (SCAP-CM) on the retinal pigmented epithelium as a single cell layer. This study investigates how SCAP-CM influences the proliferation and migration of CECs. Our results introduced Matrigel, as a new matrix component for in vitro culture of CECs. Moreover, 60% of SCAP-CM was able to stimulate CEC proliferation as well as migrate to repair wound healing during 24 h. Confluent CECs also expressed specific markers, ATP1a1, ZO-1 and CD56, indicative of CEC characteristics, aligning with the recapitulation of differentiation when forming a homogenous monolayer at the same level of isolated CECs without in vitro culture. These findings suggested that SCAP-CM administration could be useful for future preclinical and clinical applications.

角膜位于眼睛的最前端,可以折射光线,将图像聚焦在视网膜上。这种透明结构的损坏会导致各种视觉障碍。角膜内皮细胞(CECs)对透明度和平衡至关重要,但却缺乏繁殖能力。严重的损伤会导致结构破坏和视力受损。虽然大量研究旨在恢复角膜内皮层,但包括功能性单层角膜内皮细胞增殖的研究仍具有挑战性。我们之前的研究证实了来自顶端乳头调节培养基(SCAP-CM)的干细胞对视网膜色素上皮单细胞层的增殖活性。本研究探讨了SCAP-CM如何影响CECs的增殖和迁移。我们的研究结果引入了 Matrigel 作为体外培养 CECs 的新基质成分。此外,60% 的 SCAP-CM 能够刺激 CEC 增殖,并在 24 小时内迁移以修复伤口愈合。汇合的 CEC 还表达了特异性标志物 ATP1a1、ZO-1 和 CD56,表明了 CEC 的特征,这与未进行体外培养的离体 CEC 在形成同质单层时的分化再现水平一致。这些研究结果表明,施用 SCAP-CM 可用于未来的临床前和临床应用。
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引用次数: 0
An evaluation of the usability and durability of 3D printed versus standard suture materials. 评估 3D 打印与标准缝合材料的可用性和耐用性。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI: 10.1111/wrr.13175
Thang T Nguyen, Jason G Langenfeld, Benjamin C Reinhart, Elizabeth I Lyden, Abraham S Campos, Michael C Wadman, Matthew R Jamison, Stephen A Morin, Aaron N Barksdale

The capability to produce suture material using three-dimensional (3D) printing technology may have applications in remote health facilities where rapid restocking of supplies is not an option. This is a feasibility study evaluating the usability of 3D-printed sutures in the repair of a laceration wound when compared with standard suture material. The 3D-printed suture material was manufactured using a fused deposition modelling 3D printer and nylon 3D printing filament. Study participants were tasked with performing laceration repairs on the pigs' feet, first with 3-0 WeGo nylon suture material, followed by the 3D-printed nylon suture material. Twenty-six participants were enrolled in the study. Survey data demonstrated statistical significance with how well the 3D suture material performed with knot tying, 8.9 versus 7.5 (p = 0.0018). Statistical significance was observed in the 3D-printed suture's ultimate tensile strength when compared to the 3-0 Novafil suture (274.8 vs. 199.8 MPa, p = 0.0096). The 3D-printed suture also demonstrated statistical significance in ultimate extension when compared to commercial 3-0 WeGo nylon suture (49% vs. 37%, p = 0.0215). This study was successful in using 3D printing technology to manufacture suture material and provided insight into its usability when compared to standard suture material.

利用三维(3D)打印技术生产缝合材料的能力可应用于无法快速补给物资的偏远医疗机构。这是一项可行性研究,旨在评估三维打印缝合线与标准缝合材料相比在修复撕裂伤口中的可用性。三维打印缝合材料是使用熔融沉积建模三维打印机和尼龙三维打印长丝制造的。研究参与者的任务是在猪脚上进行撕裂伤修复,首先使用3-0 WeGo尼龙缝合材料,然后使用3D打印尼龙缝合材料。共有 26 人参加了这项研究。调查数据显示,三维缝合材料的打结效果具有统计学意义,8.9 对 7.5(p = 0.0018)。与 3-0 Novafil 缝线相比,三维打印缝线的极限拉伸强度具有统计学意义(274.8 对 199.8 兆帕,p = 0.0096)。与商用 3-0 WeGo 尼龙缝合线相比,3D 打印缝合线的极限延伸率也具有统计学意义(49% 对 37%,p = 0.0215)。这项研究成功地利用 3D 打印技术制造了缝合材料,并深入了解了其与标准缝合材料相比的可用性。
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引用次数: 0
3D-printed electrospun fibres for wound healing. 3D打印的用于伤口愈合的电纺纤维。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-10-10 DOI: 10.1111/wrr.13119
Xilin Ye, Enshuo Zhang, Yaqin Huang, Feng Tian, Jiajia Xue

Wound management for acute and chronic wounds has become a serious clinical problem worldwide, placing considerable pressure on public health systems. Owing to the high-precision, adjustable pore structure, and repeatable manufacturing process, 3D-printed electrospun fibre (3DP-ESF) has attracted widespread attention for fabricating wound dressing. In addition, in comparison with 2D electrospun fibre membranes fabricated by traditional electrospinning, the 3D structures provide additional guidance on cell behaviour. In this perspective article, we first summarise the basic manufacturing principles and methods to fabricate 3DP-ESF. Then, we discuss the function of 3DP-ESF in manipulating the different stages of wound healing, including anti-bacteria, anti-inflammation, and promotion of cell migration and proliferation, as well as the construction of tissue-engineered scaffolds. In the end, we provide the current challenge faced by 3DP-ESF in the application of skin wound regeneration and its promising future directions.

急性和慢性伤口的伤口管理已成为世界范围内一个严重的临床问题,给公共卫生系统带来了相当大的压力。3D打印电纺纤维(3DP-ESF)由于其高精度、可调节的孔结构和可重复的制造工艺,在制造伤口敷料方面引起了广泛关注。此外,与通过传统电纺制备的2D电纺纤维膜相比,3D结构为细胞行为提供了额外的指导。在这篇前瞻性的文章中,我们首先总结了3DP-ESF的基本制造原理和方法。然后,我们讨论了3DP-ESF在操纵伤口愈合不同阶段的作用,包括抗菌、抗炎、促进细胞迁移和增殖,以及组织工程支架的构建。最后,我们提出了3DP-ESF在皮肤伤口再生应用中面临的当前挑战及其有前景的未来方向。
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引用次数: 0
Film-forming polymer solutions containing cholesterol myristate and berberine mediate pressure ulcer repair via the Wnt/β-catenin pathway. 含有胆固醇肉豆蔻酸酯和小檗碱的成膜聚合物溶液通过 Wnt/β-catenin 通路介导褥疮修复。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-02-14 DOI: 10.1111/wrr.13158
Yu Li, Haiting Huang, Cuijin Gu, Wenyi Huang, Xianxian Chen, Xiaoting Lu, Aijia You, Sen Ye, Jun Zhong, Yao Zhao, Yu Yan, Chun Li

Pressure ulcer (PU) is a worldwide problem that is difficult to address because of the related inflammatory response, local hypoxia, and repeated ischaemia/reperfusion, causing great suffering and financial burden to patients. Traditional Chinese medicine turtle plate powder can treat skin trauma, but its composition is complex and inconvenient to use. Here, we combined cholesterol myristate (S8) with berberine (BBR), with anti-inflammatory and antibacterial effects, as a drug and used hydroxypropyl methylcellulose and polyvinylpyrrolidone K30 as carriers to construct a novel film-forming polymeric solution (S8 + BBR FFPS), comprehensively study its reparative effect on PU and explore the potential mechanism in rat PU models. The results showed that S8 + BBR FFPS inhibits excessive inflammatory response, promotes re-epithelialization, and promotes hair follicle growth during the healing process of PU, which may be related to the activation of the Wnt/β-catenin signalling pathway by S8 + BBR FFPS to mediate hair follicle stem cell proliferation and maintain skin homeostasis. Therefore, S8 + BBR FFPS may be a potential candidate for the treatment of chronic skin injury, and its association with the Wnt/β-catenin signalling pathway may provide new ideas to guide the design of biomaterial-based wound dressings for chronic wound repair.

褥疮(PU)是一个难以解决的世界性难题,因为相关的炎症反应、局部缺氧和反复缺血/再灌注,给患者造成了巨大的痛苦和经济负担。传统中药龟板散可治疗皮肤创伤,但其成分复杂,使用不便。在此,我们将胆固醇肉豆蔻酸酯(S8)与具有消炎抗菌作用的小檗碱(BBR)作为药物,以羟丙基甲基纤维素和聚乙烯吡咯烷酮 K30 为载体,构建了一种新型成膜聚合物溶液(S8 + BBR FFPS),全面研究了其对 PU 的修复作用,并在大鼠 PU 模型中探索了其潜在机制。结果表明,S8 + BBR FFPS 在 PU 愈合过程中可抑制过度炎症反应,促进上皮重建,促进毛囊生长,这可能与 S8 + BBR FFPS 激活 Wnt/β-catenin 信号通路,介导毛囊干细胞增殖,维持皮肤稳态有关。因此,S8 + BBR FFPS 可能是治疗慢性皮肤损伤的潜在候选药物,它与 Wnt/β-catenin 信号通路的关联可能为指导设计用于慢性伤口修复的生物材料伤口敷料提供了新思路。
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引用次数: 0
Human keratin matrices promote wound healing by modulating skin cell expression of cytokines and growth factors. 人类角蛋白基质通过调节皮肤细胞对细胞因子和生长因子的表达,促进伤口愈合。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-01-02 DOI: 10.1111/wrr.13137
Allison N Ramey-Ward, Howard P Walthall, Shakesia Smith, Thomas H Barrows

A wide variety of biomaterials has been developed to assist in wound healing, including acellular animal and human-derived protein matrices. However, millions of patients worldwide still suffer from non-healing chronic wounds, demonstrating a need for further innovation in wound care. To address this need, a novel biomaterial, the human keratin matrix (HKM), was developed, characterised, and tested in vitro and in vivo. HKM was found to be degradation-resistant, and a proteomics analysis showed it to be greater than 99% human keratin proteins. PCR revealed adult human epidermal keratinocytes (HEKa) grown in contact with HKM showed increased gene expression of keratinocyte activations markers such as Epidermal Growth Factor (EGF). Additionally, a cytokine microarray demonstrated culture on HKM increased the release of cytokines involved in wound inflammatory modulation by both HEKa cells and adult human dermal fibroblasts (HDFa). Finally, in a murine chronic wound model, full-thickness wounds treated weekly with HKM were smaller through the healing process than those treated with human amniotic membrane (AM), bovine dermis (BD), or porcine decellularized small intestinal submucosa (SIS). HKM-treated wounds also closed significantly faster than AM- and SIS-treated wounds. These data suggest that HKM is an effective novel treatment for chronic wounds.

目前已开发出多种有助于伤口愈合的生物材料,包括无细胞动物和人源蛋白基质。然而,全球仍有数百万患者的慢性伤口无法愈合,这表明伤口护理需要进一步创新。为了满足这一需求,我们开发了一种新型生物材料--人角蛋白基质(HKM),并对其进行了表征和体内外测试。研究发现 HKM 具有抗降解性,蛋白质组学分析表明它含有 99% 以上的人类角蛋白。PCR 显示,与 HKM 接触生长的成人表皮角质细胞(HEKa)显示,表皮生长因子(EGF)等角质细胞活化标志物的基因表达增加。此外,细胞因子芯片显示,在 HKM 上培养的 HEKa 细胞和成人真皮成纤维细胞(HDFa)释放的细胞因子参与了伤口炎症调节。最后,在小鼠慢性伤口模型中,与使用人羊膜(AM)、牛真皮(BD)或猪脱细胞小肠粘膜(SIS)处理的伤口相比,每周使用 HKM 处理的全厚伤口在愈合过程中更小。经 HKM 处理的伤口闭合速度也明显快于经 AM 和 SIS 处理的伤口。这些数据表明,HKM 是一种有效的慢性伤口新疗法。本文受版权保护。保留所有权利。
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引用次数: 0
Progress in copper-based materials for wound healing. 用于伤口愈合的铜基材料的进展。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-10-21 DOI: 10.1111/wrr.13122
Wuliang Diao, Peiting Li, Xilin Jiang, Jianda Zhou, Songbo Yang

Chronic wounds have become the leading cause of death, particularly among diabetic patients. Chronic wounds affect ~6.5 million patients each year, according to statistics, and wound care and management incur significant financial costs. The rising prevalence of chronic wounds, combined with the limitations of current treatments, necessitates the development of new and innovative approaches to accelerate wound healing. Copper has been extensively studied for its antibacterial and anti-inflammatory activities. Copper in its nanoparticle form could have better biological properties and many applications in health care.

慢性伤口已成为死亡的主要原因,尤其是在糖尿病患者中。据统计,慢性伤口每年影响约650万名患者,伤口护理和管理产生了巨大的经济成本。慢性伤口的患病率不断上升,再加上目前治疗方法的局限性,需要开发新的创新方法来加速伤口愈合。铜因其抗菌和抗炎活性而被广泛研究。纳米颗粒形式的铜可能具有更好的生物特性,并在医疗保健中有许多应用。这篇文章受版权保护。保留所有权利。
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引用次数: 0
Development of a double-layer electrospun patch as a potential prenatal treatment for myelomeningocele. 双层电纺丝贴片的发展作为一种潜在的产前治疗脊髓脊膜膨出。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2023-12-04 DOI: 10.1111/wrr.13123
K Benabdderrahmane, J Stirnemann, S Ramtani, C Falentin-Daudré

Myelomeningocele (MMC) is a congenital defect of the spine characterised by meningeal and spinal cord protrusion through the open vertebral arches. This defect causes progressive prenatal damage of the spinal cord, leading to lifelong handicap. Although mid-trimester surgical repair may reduce part of the handicap, an earlier and less invasive approach would further improve the prognosis, possibly minimising maternal and foetal risks. Several studies have proposed an alternative approach to surgical repair by covering the defect with a patch and protecting the exposed neural tissue. Our study aims to elaborate on a waterproof and biodegradable bioactive patch for MMC prenatal foetal repair. We developed a double-layer patch that can provide a waterproof coverage for the spinal cord, with a bioactive side, conducive to cell proliferation, and an antiadhesive side to avoid its attachment to the medulla.

脊髓脊膜膨出(MMC)是一种先天性脊柱缺陷,其特征是脑膜和脊髓通过开放的椎弓突出。这种缺陷会导致脊髓进行性产前损伤,导致终生残疾。虽然中期手术修复可能会减少部分障碍,但更早和更小的侵入性方法将进一步改善预后,可能最大限度地减少产妇和胎儿的风险。一些研究提出了一种手术修复的替代方法,即用贴片覆盖缺损并保护暴露的神经组织。本研究旨在研制一种防水、可生物降解的MMC产前胎儿修复生物活性贴片。我们开发了一种双层贴片,可以为脊髓提供防水覆盖,具有生物活性的一面,有利于细胞增殖,以及抗粘附的一面,以避免其附着在髓质上。这篇文章受版权保护。版权所有。
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引用次数: 0
Utilizing multiscale engineered biomaterials to examine TGF-β-mediated myofibroblastic differentiation. 利用多尺度工程生物材料研究 TGF-β 介导的肌成纤维细胞分化。
IF 3.8 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-01 Epub Date: 2024-03-09 DOI: 10.1111/wrr.13168
Aryssa Simpson, Abhichart Krissanaprasit, Daniel Chester, Cynthia Koehler, Thomas H LaBean, Ashley C Brown

Cells integrate many mechanical and chemical cues to drive cell signalling responses. Because of the complex nature and interdependency of alterations in extracellular matrix (ECM) composition, ligand density, mechanics, and cellular responses it is difficult to tease out individual and combinatorial contributions of these various factors in driving cell behavior in homeostasis and disease. Tuning of material viscous and elastic properties, and ligand densities, in combinatorial fashions would enhance our understanding of how cells process complex signals. For example, it is known that increased ECM mechanics and transforming growth factor beta (TGF-β) receptor (TGF-β-R) spacing/clustering independently drive TGF-β signalling and associated myofibroblastic differentiation. However, it remains unknown how these inputs orthogonally contribute to cellular outcomes. Here, we describe the development of a novel material platform that combines microgel thin films with controllable viscoelastic properties and DNA origami to probe how viscoelastic properties and nanoscale spacing of TGF-β-Rs contribute to TGF-β signalling and myofibroblastic differentiation. We found that highly viscous materials with non-fixed TGF-β-R spacing promoted increased TGF-β signalling and myofibroblastic differentiation. This is likely due to the ability of cells to better cluster receptors on these surfaces. These results provide insight into the contribution of substrate properties and receptor localisation on downstream signalling. Future studies allow for exploration into other receptor-mediated processes.

细胞整合了许多机械和化学线索来驱动细胞信号反应。由于细胞外基质(ECM)成分、配体密度、力学和细胞反应的变化性质复杂且相互依存,因此很难分清这些不同因素在驱动细胞平衡和疾病行为中的单独和组合作用。以组合方式调整材料的粘性和弹性特性以及配体密度,将有助于我们更好地了解细胞如何处理复杂信号。例如,已知 ECM 力学和转化生长因子 beta(TGF-β)受体(TGF-β-R)间距/集群的增加可独立驱动 TGF-β 信号和相关的肌成纤维细胞分化。然而,这些输入如何正交作用于细胞结果仍是未知数。在此,我们介绍了一种新型材料平台的开发情况,该平台结合了具有可控粘弹性的微凝胶薄膜和 DNA 折纸,以探究粘弹性特性和 TGF-β-R 的纳米级间距如何促进 TGF-β 信号传导和肌成纤维细胞分化。我们发现,具有非固定 TGF-β-R 间距的高粘度材料可促进 TGF-β 信号传导和肌成纤维细胞分化。这可能是由于细胞能更好地将受体聚集在这些表面上。这些结果让我们深入了解了底物特性和受体定位对下游信号传导的贡献。未来的研究还将探索其他受体介导的过程。
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引用次数: 0
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Wound Repair and Regeneration
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