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Sulfated poly(aspartic acid) coatings as next-generation biomimetic interfaces for blood-contacting devices 硫酸聚天冬氨酸涂层作为血液接触装置的下一代仿生界面
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-19 DOI: 10.1016/j.bioadv.2026.214723
Cuong Hung Luu , Akriti Nepal , Nam-Trung Nguyen , Hang Thu Ta
The increasing reliance on blood-contacting medical devices underscores the need for materials that minimise thrombosis and inflammation. Devices such as stents and dialysis membranes often face complications related to clot formation and microbial colonisation. To address these challenges, this study explored the development of sulfated poly(aspartic acid) (sPASP) coatings aimed at improving haemocompatibility and reducing infection risk. PASP, a biodegradable, biocompatible polymer, and calcium chelator, served as the base material, with sulfation introduced to enhance its antithrombotic, antibacterial, and anti-inflammatory properties. Sulfate groups mimic natural anticoagulants such as heparin, potentially promoting antithrombin activity and inhibiting clot development. The coatings were fabricated via a simplified one-pot process on polydopamine-modified substrates. The degree of sulfation was systematically varied from 10% to 80% to optimise the material's performance and thoroughly evaluated across multiple dimensions of blood compatibility. Assessments included surface physicochemical properties, protein adsorption, platelet adhesion, antithrombotic efficacy, cellular compatibility, and antibacterial activity, under static and dynamic conditions. Notably, sPASP with a sulfation degree of 40% exhibited the most favourable blood compatibility, demonstrating strong potential compared to heparin-mimicking polysaccharide coatings. In addition, the material exhibited excellent in vivo biocompatibility in implantation models, further underscoring its promise as a high-performance, multifunctional biomimetic interface for blood-contacting biomedical applications.
对血液接触医疗设备的日益依赖强调了对最小化血栓和炎症的材料的需求。支架和透析膜等设备经常面临与血栓形成和微生物定植有关的并发症。为了应对这些挑战,本研究探索了磺化聚天冬氨酸(sPASP)涂层的开发,旨在改善血液相容性并降低感染风险。PASP是一种可生物降解的、生物相容的聚合物和钙螯合剂,作为基础材料,引入硫酸化以增强其抗血栓、抗菌和抗炎性能。硫酸盐基团模拟天然抗凝血剂,如肝素,潜在地促进抗凝血酶活性和抑制凝块的发展。采用简化的一锅工艺在聚多巴胺修饰的基底上制备涂层。磺化程度系统地从10%到80%变化,以优化材料的性能,并在血液相容性的多个维度上进行全面评估。评估包括在静态和动态条件下的表面物理化学性质、蛋白质吸附、血小板粘附、抗血栓疗效、细胞相容性和抗菌活性。值得注意的是,磺化度为40%的sPASP具有最有利的血液相容性,与模拟肝素的多糖涂层相比,显示出强大的潜力。此外,该材料在植入模型中表现出良好的体内生物相容性,进一步强调了其作为血液接触生物医学应用的高性能,多功能仿生界面的前景。
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引用次数: 0
Theranostic platforms for skin tissue engineering: Bridging healing and real-time monitoring 皮肤组织工程的治疗平台:桥接愈合和实时监测
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-19 DOI: 10.1016/j.bioadv.2026.214724
Lidia Maeso , Mohammadsadegh Nadimifar , Saptarshi Biswas , Shounak Roy , Akhilesh K. Gaharwar , Alireza Dolatshahi-Pirouz , Gorka Orive
Chronic wounds are a major healthcare challenge, contributing to significant morbidity and reduced quality of life while imposing a substantial economic burden on healthcare systems. Traditional wound care approaches often fail to provide real-time feedback on treatment efficacy, limiting the ability to adapt therapeutic strategies dynamically. Theranostic platforms, which can integrate both diagnostic and therapeutic functionalities, have emerged as a promising solution to bridge this gap. These advanced systems enable continuous monitoring of key wound parameters, such as temperature, pH, oxygen levels, glucose, and reactive oxygen species (ROS), while simultaneously delivering targeted therapies, including drug release, gene and cell therapies, immunomodulation, and photothermal or photodynamic treatments. By incorporating both healing and monitoring capabilities into acellular scaffolds, hydrogel-based matrices, self-healing hydrogels, and 3D-bioprinted skin substitutes, researchers aim to optimize therapeutic efficacy and improve clinical outcomes. This review explores the different platforms available for skin tissue engineering that serve as the foundation for theranostic systems, alongside the most relevant diagnostic and therapeutic strategies for enhanced wound healing, and discusses future directions and challenges in this evolving field.
慢性伤口是一项重大的卫生保健挑战,导致显著发病率和生活质量下降,同时给卫生保健系统带来巨大的经济负担。传统的伤口护理方法往往不能提供治疗效果的实时反馈,限制了动态适应治疗策略的能力。可以整合诊断和治疗功能的治疗平台已经成为弥合这一差距的有希望的解决方案。这些先进的系统能够持续监测关键伤口参数,如温度、pH值、氧气水平、葡萄糖和活性氧(ROS),同时提供靶向治疗,包括药物释放、基因和细胞治疗、免疫调节、光热或光动力治疗。通过将愈合和监测功能结合到无细胞支架、水凝胶基质、自修复水凝胶和3d生物打印皮肤替代品中,研究人员旨在优化治疗效果并改善临床结果。这篇综述探讨了作为治疗系统基础的皮肤组织工程的不同平台,以及促进伤口愈合的最相关的诊断和治疗策略,并讨论了这一不断发展的领域的未来方向和挑战。
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引用次数: 0
Piezoelectric nanocomposite patch for self-powered bioelectrical stimulation for cardiac tissue engineering 用于心脏组织工程自供电生物电刺激的压电纳米复合贴片。
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-17 DOI: 10.1016/j.bioadv.2026.214717
Hyunjin Kim , Kannan Badri Narayanan , Vineet Kumar , Sung Soo Han , Rakesh Bhaskar
Cardiovascular diseases remain the leading cause of mortality worldwide, and myocardial infarction results in irreversible loss of functional myocardium with limited regenerative treatment options. Here, we report a self-responsive piezoelectric elastomeric patch designed for cardiac tissue engineering (CTE) by integrating dual nanofillers (TiC and MoS₂; 2 phr each) into a polydimethylsiloxane (PDMS) matrix and following a PLA/PDMS electrospun nanofiber coating as a temporary biointerface to promote early cell attachment. Composite patches (PDMS, PDMS+TiC, PDMS+MoS₂, and Hybrid) were fabricated by casting/curing and coated at a semi-cured stage to enable physical interlocking of the fiber layer. The materials were characterized by SEM, FTIR, XRD, XPS, wettability measurements, compressive testing, and TGA/DTGA. Electromechanical performance was assessed by cyclic compression (30% strain), and biological performance was evaluated using NIH3T3 fibroblasts (MTT, Live/Dead, and intracellular ROS assays) and H9c2 cardiomyoblasts on fiber-coated configurations under low-intensity agitation. The Hybrid patch exhibited balanced mechanical reinforcement and reproducible voltage generation (typically ±20–30 mV) under cyclic loading. All formulations maintained cytocompatibility, while the Hybrid group reduced intracellular ROS compared with single-filler composites and supported improved cell adhesion/spreading when combined with the nanofiber interface. These findings demonstrate a mechanically robust, electrically responsive, and cytocompatible PDMS-based hybrid scaffold with a degradable fibrous bio-interface, providing a foundation for self-powered, mechanically interactive cardiac patch platforms.
心血管疾病仍然是世界范围内死亡的主要原因,心肌梗死导致功能心肌的不可逆转丧失,再生治疗选择有限。在这里,我们报道了一种为心脏组织工程(CTE)设计的自响应压电弹性体贴片,通过将双纳米填料(TiC和MoS 2;每个2 phr)集成到聚二甲基硅氧烷(PDMS)基质中,并在PLA/PDMS电纺纳米纤维涂层下作为临时生物界面来促进早期细胞附着。复合贴片(PDMS、PDMS+TiC、PDMS+MoS 2和Hybrid)通过铸造/固化制成,并在半固化阶段涂覆,以实现纤维层的物理互锁。通过SEM、FTIR、XRD、XPS、润湿性测试、压缩测试和TGA/DTGA对材料进行表征。通过循环压缩(30%应变)评估机电性能,并使用NIH3T3成纤维细胞(MTT, Live/Dead和细胞内ROS测定)和H9c2成心肌细胞在低强度搅拌下对纤维包覆配置进行生物性能评估。混合贴片在循环加载下具有平衡的机械增强和可重复的电压产生(通常为±20-30 mV)。所有配方都保持了细胞相容性,而与单填料复合材料相比,Hybrid组减少了细胞内ROS,并在与纳米纤维界面结合时支持改善细胞粘附/扩散。这些发现证明了一种具有可降解纤维生物界面的机械坚固、电响应和细胞相容性的基于pdms的混合支架,为自供电、机械交互的心脏贴片平台提供了基础。
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引用次数: 0
Regulation of osteogenic differentiation of boronized Ti6Al4V/HA composite involving TRIP13-PI3K/Akt signaling pathway 通过TRIP13-PI3K/Akt信号通路调控硼化Ti6Al4V/HA复合物成骨分化
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-17 DOI: 10.1016/j.bioadv.2026.214720
Yihong Chen , Xiaojie Chen , Boyu Liu , Hengrong Xiong , Zhiwei Peng , Qian Peng
Titanium and its alloys are widely used in dental implants owing to their excellent biocompatibility and corrosion resistance, despite their elastic moduli mismatch with bone and insufficient interfacial bioactivity which often restrict their osseointegration performance, particularly in the early stage after implantation. To address these limitations, a boronized Ti6Al4V/hydroxyapatite (HA) composite with improved structural and biological performance was developed. Scanning electron microscopy and atomic force microscopy confirmed a micro/nanostructured surface with increased roughness. RNA sequencing of osteoblasts cultured on the composite identified 683 upregulated and 838 downregulated genes relative to Ti6Al4V. Gene ontology enrichment revealed biological processes related to cell adhesion, extracellular matrix remodeling, and integrin-mediated signaling, whereas KEGG pathway analysis indicated activation of cell cycle, PI3K/Akt, and calcium signaling pathways. Gene set variation analysis further highlighted eight key upregulated genes-CYP1A1, CRLF2, HBEGF, IRAK2, DLL1, CYP1B1, BLOC1S5-TXNDC5, and TRIP13. Functional validation demonstrated that the TRIP13 expression correlated positively with osteogenic differentiation, in conjunction with activation of the PI3K/Akt signaling pathway. Collectively, these findings proved a TRIP13-associated transcriptional response linked to osteogenic regulation on the boronized Ti6Al4V/HA composite surface, offering a mechanistic insight into the design of bioactive titanium-based implants with improved osseointegration.
钛及其合金由于其优异的生物相容性和耐腐蚀性被广泛应用于牙科种植体中,尽管其弹性模量与骨不匹配以及界面生物活性不足往往限制了其骨整合性能,特别是在种植后的早期。为了解决这些限制,开发了一种具有改进结构和生物性能的硼化Ti6Al4V/羟基磷灰石(HA)复合材料。扫描电子显微镜和原子力显微镜证实了微/纳米结构表面粗糙度增加。在复合材料上培养的成骨细胞的RNA测序鉴定出与Ti6Al4V相关的683个上调基因和838个下调基因。基因本体富集揭示了与细胞粘附、细胞外基质重塑和整合素介导的信号通路相关的生物学过程,而KEGG通路分析显示了细胞周期、PI3K/Akt和钙信号通路的激活。基因集变异分析进一步发现了8个关键的上调基因:cyp1a1、CRLF2、HBEGF、IRAK2、DLL1、CYP1B1、BLOC1S5-TXNDC5和TRIP13。功能验证表明,TRIP13的表达与成骨分化呈正相关,并与PI3K/Akt信号通路的激活有关。总的来说,这些发现证明了trip13相关的转录反应与硼化Ti6Al4V/HA复合材料表面的成骨调节有关,为设计具有改善骨整合性的生物活性钛基植入物提供了机制见解。
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引用次数: 0
Oral delivery of liraglutide using CPP/hyaluronic acid-modified mesoporous silica nanoparticles: A virus-inspired strategy for intestinal absorption 使用CPP/透明质酸修饰的介孔二氧化硅纳米颗粒口服利拉鲁肽:一种病毒激发的肠道吸收策略
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-14 DOI: 10.1016/j.bioadv.2026.214714
Narges Shams , Mehdi Esfandyari-Manesh , Mohammad Sharifzadeh , Mohsen Amini , Yousef Fatahi , Rassoul Dinarvand
Oral administration of peptide-based drugs offers improved patient compliance compared to injectable formulations. However, this route is hindered by several physiological barriers like enzymatic degradation, poor intestinal permeability, and low absorption in the gastrointestinal tract. To address these challenges, a novel virus-mimicking nanocarrier was developed for the oral delivery of liraglutide. Hollow mesoporous silica nanoparticles (HMSN) were synthesized via a co-condensation method and subsequently functionalized with a positively charged cell-penetrating peptide (CPP; KLPVM) to facilitate transcellular transport, and with negatively charged hyaluronic acid (HA) to enhance mucus penetration and enable receptor-mediated targeting. Liraglutide was efficiently encapsulated within HMSN matrix, achieving an encapsulation efficiency of 96.16% and a drug loading of 19.23%. In vitro release studies showed pH-responsive behavior, with limited release under acidic gastric conditions (7%) and sustained release at near-neutral intestinal pH (77% over 12 h). Cellular uptake studies revealed enhanced internalization of the HMSN-CPP@HA (98.1%), predominantly via caveolae-mediated endocytosis. Ex vivo intestinal permeability studies further confirmed improved transmucosal transport, with permeability increasing from 34.4% for MSNs to 97.6% for HMSN-CPP@HA. Pharmacodynamic evaluation in streptozotocin-induced diabetic rat models showed that oral administration of liraglutide-loaded virus-mimicking HMSNs resulted in a 50.98% reduction in fasting blood glucose and a 14.6% decrease in body weight over 28-day period. These outcomes were comparable to those achieved via subcutaneous liraglutide administration (62.7% and 19.2% respectively). These findings suggest that HMSN-CPP@HA preserve the biological activity of liraglutide during gastrointestinal transit, enhance intestinal absorption, and mimic viral translocation mechanisms, representing a promising platform for non-invasive oral delivery of peptide drugs.
与注射制剂相比,口服肽类药物可改善患者的依从性。然而,这一途径受到一些生理障碍的阻碍,如酶降解、肠道渗透性差和胃肠道吸收低。为了解决这些挑战,研究人员开发了一种用于口服利拉鲁肽的新型病毒模拟纳米载体。中空介孔二氧化硅纳米颗粒(HMSN)通过共缩合方法合成,随后与带正电荷的细胞穿透肽(CPP; KLPVM)功能化以促进跨细胞运输,并与带负电荷的透明质酸(HA)功能化以增强粘液渗透并实现受体介导的靶向。利拉鲁肽被高效地包封在HMSN基质中,包封率为96.16%,载药量为19.23%。体外释放研究显示出pH响应行为,在酸性胃条件下释放有限(7%),在接近中性的肠道pH下持续释放(超过12小时77%)。细胞摄取研究显示HMSN-CPP@HA(98.1%)的内化增强,主要通过小泡介导的内吞作用。体外肠通透性研究进一步证实了MSNs改善了粘膜运输,通透性从34.4%增加到HMSN-CPP@HA的97.6%。在链脲佐菌素诱导的糖尿病大鼠模型中进行的药效学评估显示,在28天的时间内,口服利拉鲁肽模拟病毒的HMSNs可使空腹血糖降低50.98%,体重降低14.6%。这些结果与皮下利拉鲁肽获得的结果相当(分别为62.7%和19.2%)。这些发现表明HMSN-CPP@HA在胃肠道转运过程中保留利拉鲁肽的生物活性,增强肠道吸收,并模拟病毒易位机制,代表了一个有前途的无创口服肽药物平台。
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引用次数: 0
Mesoporous polydopamine loaded with silver nanoparticles and quercetin for bacterial keratitis treatment through antibacterial and anti-angiogenic mechanisms 负载银纳米粒子和槲皮素的介孔聚多巴胺通过抗菌和抗血管生成机制治疗细菌性角膜炎。
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-14 DOI: 10.1016/j.bioadv.2026.214715
Meiliang Wu , Rong Liu , Weijin Nan , Can Meng , Wenxin Zhang , Qingyu Guo , Hong Wu
Bacterial keratitis (BK) is a serious blinding eye disease, with pathological features mainly including corneal stromal opacity, edema, inflammatory response, and corneal neovascularization (CoNV). Timely intervention and treatment are required in clinical practice. In this study, we successfully prepared mesoporous polydopamine (MPDA) using a soft-template method, and further introduced silver nanoparticles (Ag NPs) and quercetin (Que) onto its surface, resulting in the effective preparation of a Q/AMP nanocomposite with dual functions of anti-angiogenesis and antibacterial activity, which is expected to be applied in the prevention and treatment of BK. The experimental results demonstrated that Q/AMP, based on favorable in vitro and in vivo biocompatibility, effectively inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs), as well as markedly inhibited CoNV in rats. In the in vitro antibacterial experiment, Q/AMP exhibited broad-spectrum and highly efficient antibacterial activity. In the BK animal model, Q/AMP achieved a 97.0% antibacterial rate, higher than Levofloxacin (LVFX) eye drops (77.4%), and Q/AMP showed a greater therapeutic effect, reducing corneal opacity score from 2.5 with LVFX to 0.8 and effectively alleviating ocular symptoms. Therefore, this study presents a promising new strategy for the treatment of infectious keratitis. Q/AMP has demonstrated strong capabilities in antibacterial, anti-angiogenic, and anti-inflammatory aspects, which may attract more attention to the deeper integration of biomaterials and infectious keratitis research.
细菌性角膜炎(BK)是一种严重的致盲眼病,其病理特征主要包括角膜基质混浊、水肿、炎症反应和角膜新生血管(CoNV)。在临床实践中需要及时干预和治疗。在本研究中,我们采用软模板法成功制备了介孔聚多巴胺(MPDA),并在其表面进一步引入银纳米粒子(Ag NPs)和槲皮素(Que),从而有效制备了具有抗血管生成和抗菌双重功能的Q/AMP纳米复合材料,有望应用于BK的防治。基于良好的体外和体内生物相容性,有效抑制人脐静脉内皮细胞(HUVECs)的增殖、迁移和成管,并显著抑制大鼠体内的CoNV。在体外抗菌实验中,Q/AMP表现出广谱、高效的抗菌活性。在BK动物模型中,Q/AMP的抗菌率达到97.0%,高于左氧氟沙星(LVFX)滴眼液的77.4%,并且Q/AMP的治疗效果更明显,将角膜混浊评分从LVFX的2.5分降低到0.8分,有效缓解眼部症状。因此,本研究为感染性角膜炎的治疗提供了一个有希望的新策略。Q/AMP在抗菌、抗血管生成和抗炎方面表现出较强的能力,可能会引起人们对生物材料与感染性角膜炎研究更深层次结合的关注。
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引用次数: 0
Polymeric micelles for encapsulation of plant-derived bioactives: a decade of advances in antimicrobial, antitumor, and antioxidant applications 高分子胶束包封植物源性生物活性物质:抗菌、抗肿瘤和抗氧化应用的十年进展
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-11 DOI: 10.1016/j.bioadv.2026.214713
Astrid Corrales , James Villar , Ana Lívia de Carvalho Bovolato , Alberto Gomes Tavares Júnior , Rita de Cássia Lacerda Brambilla Rodrigues , Marlus Chorilli , Daniele Ribeiro de Araujo , André Moreni Lopes
This 10-year review provides a comprehensive overview of advances in the use of polymeric micelles (PMs) for the encapsulation of bioactive compounds derived from renewable green sources. PMs have emerged as highly versatile nanocarriers that capable of enhancing the solubility, stability, and bioavailability of poorly water-soluble compounds while enabling controlled and targeted release. Across the literature, PM formulations typically exhibit nanoscale sizes ranging from ∼10 to 200 nm, low polydispersity indices (generally <0.300), and high encapsulation efficiencies, commonly ranging from ∼70 to >95%. By protecting plant-derived bioactives from degradation and enabling sustained release profiles over hours to days, PMs significantly improve antimicrobial, antitumor, and antioxidant performance, frequently reducing effective concentrations compared to free compounds. The incorporation of green-source biomolecules adds further value through their natural origin, biocompatibility, low toxicity, and alignment with sustainability-driven pharmaceutical development. This review critically analyzes the physicochemical parameters governing PM performance, including particle size, surface charge, encapsulation efficiency, and release kinetics, and correlates these features with biological activity and therapeutic outcomes. Special emphasis is placed on key formulation strategies reported over the past decade, highlighting PMs as a rapidly evolving and high-performance platform for the development of safer, more efficient, and innovative nanomedicine.
这10年的回顾提供了一个全面的综述,在使用聚合物胶束(pm)包封生物活性化合物从可再生的绿色来源。pm已经成为高度通用的纳米载体,能够提高水溶性差化合物的溶解度、稳定性和生物利用度,同时实现控制和靶向释放。在文献中,PM配方通常具有纳米级尺寸范围为~ 10至200nm,低多分散性指数(通常为<;0.300)和高封装效率,通常范围为~ 70%至>;95%。通过保护植物源性生物活性免遭降解,并在数小时至数天内实现持续释放,pmms显著提高了抗菌、抗肿瘤和抗氧化性能,与游离化合物相比,pmms的有效浓度经常降低。绿色来源生物分子的结合通过其天然来源,生物相容性,低毒性以及与可持续驱动的药物开发相一致而增加了进一步的价值。这篇综述批判性地分析了控制PM性能的物理化学参数,包括粒径、表面电荷、包封效率和释放动力学,并将这些特征与生物活性和治疗结果联系起来。特别强调了过去十年中报告的关键配方策略,强调了pm作为开发更安全,更有效和创新的纳米药物的快速发展和高性能平台。
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引用次数: 0
A novel antimicrobial peptide AH-12 attenuates mitochondrial response to inflammatory stimuli and prevents periodontitis via antibacterial and anti-inflammatory effects 一种新型抗菌肽AH-12减弱线粒体对炎症刺激的反应,并通过抗菌和抗炎作用预防牙周炎
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-09 DOI: 10.1016/j.bioadv.2026.214711
Yuanchen Wang , Shuting Zhang , Jinrong Sun , Qian Zhang , Xi Zhang
Antibiotic-assisted periodontal therapy remains a primary clinical strategy, yet the rising prevalence of bacterial resistance severely compromises its therapeutic efficacy. To address this challenge, antimicrobial peptides (AMPs) have emerged as promising alternatives owing to their distinct antibacterial mechanisms. Here, we developed a novel antimicrobial peptide, AH-12, by systematically optimizing P-113—the minimal inhibitory fragment of human salivary Histatin 5—through N-terminal modification, amidation, and acetylation. In vitro evaluations demonstrated potent inhibitory effects of AH-12 against key oral pathogens (Fusobacterium nucleatum, Porphyromonas gingivalis, and Streptococcus gordonii), achieved via bacterial membrane lysis and suppression of FadA adhesin secretion in F. nucleatum. Beyond its antibacterial properties, AH-12 targeted inflammatory regulation by modulating mitochondrial function. Mitochondria, as early responders to inflammation, drive inflammatory cascades via Ca2+-dependent signaling. Remarkably, AH-12 stabilized mitochondrial Ca2+ levels, thereby attenuating mitochondrial reactive oxygen species (mtROS) overproduction and mitochondrial DNA (mtDNA) release, which collectively contributed to its robust anti-inflammatory effects. In order to minimize the loss of medication during administration and to better fit the shape of the periodontal pockets, a GelMA hydrogel (GelMA@AH-12) was engineered for controlled release applications. In vivo studies validated the outstanding efficacy of GelMA@AH-12, highlighting AH-12 as a transformative candidate for periodontitis treatment.
抗生素辅助牙周治疗仍然是一种主要的临床策略,但细菌耐药性的日益流行严重影响了其治疗效果。为了解决这一挑战,抗菌肽(AMPs)由于其独特的抗菌机制而成为有希望的替代品。在这里,我们通过n端修饰、酰胺化和乙酰化,系统地优化了人类唾液组蛋白5的最小抑制片段p -113,开发了一种新的抗菌肽AH-12。体外评估表明,AH-12对口腔主要病原体(核梭菌、牙龈卟啉单胞菌和戈登链球菌)有有效的抑制作用,这是通过细菌膜裂解和抑制核梭菌中FadA粘连素的分泌来实现的。除了抗菌特性,AH-12还通过调节线粒体功能来调节炎症。线粒体作为炎症的早期反应者,通过Ca2+依赖性信号驱动炎症级联反应。值得注意的是,AH-12稳定了线粒体Ca2+水平,从而减少了线粒体活性氧(mtROS)的过量产生和线粒体DNA (mtDNA)的释放,这共同促成了其强大的抗炎作用。为了最大限度地减少药物在给药过程中的损失,并更好地适应牙周袋的形状,GelMA水凝胶(GelMA@AH-12)被设计用于控释应用。体内研究证实了GelMA@AH-12的卓越功效,突出了AH-12作为牙周炎治疗的变革性候选药物。
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引用次数: 0
An antagomiR-loaded β-peptide hydrogel promotes functional recovery in mice post-ischaemic stroke 一种含有安他戈米的β肽水凝胶促进小鼠缺血性中风后的功能恢复。
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-09 DOI: 10.1016/j.bioadv.2026.214712
Yi-Kai Chen , Ketav Kulkarni , Marie-Isabel Aguilar , Brad R.S. Broughton , Mark P. Del Borgo
Ischaemic stroke is a leading cause of mortality and disability, arising from interrupted cerebral blood flow and subsequent neuronal death. MicroRNAs, particularly miR-181a, have emerged as promising therapeutic targets due to their roles in regulating apoptosis and oxidative stress. While miR-181a inhibition using antagomirs can improve neuronal survival, translation to clinical practice is hampered by inefficient delivery across the blood–brain barrier and poor pharmacokinetics. Here, we developed a series of novel β-peptide hydrogels as injectable delivery systems to encapsulate and release a miR-181a antagomir in a controlled manner within the infarct region. β-peptides were synthesised with varied incorporation of β-homolysine residues to modulate electrostatic interactions with nucleic acids. The resulting hydrogels demonstrated shear-thinning and self-healing properties, stiffness values within the physiological range of brain tissue and tunable nucleic acid release profiles extending over 3 weeks. Following photothrombotic stroke in mice, intracerebral injection of antagomir-loaded hydrogel achieved precise infarct delivery and sustained presence for at least 7 days. Although infarct size reduction was modest, functional recovery, measured by improved motor coordination in the hanging wire test, was significantly enhanced in the hydrogel-antagomir group compared with controls. These findings highlight β-peptide hydrogels as promising platforms for localised, sustained delivery of nucleic acid therapeutics. This work establishes proof-of-concept for hydrogel-mediated miRNA delivery in stroke and provides a foundation for further optimisation in clinically relevant models.
缺血性中风是死亡和残疾的主要原因,由脑血流中断和随后的神经元死亡引起。microrna,特别是miR-181a,由于其在调节细胞凋亡和氧化应激中的作用,已经成为有希望的治疗靶点。虽然使用安塔戈米抑制miR-181a可以改善神经元存活,但通过血脑屏障的低效递送和不良的药代动力学阻碍了转化为临床实践。在这里,我们开发了一系列新型β-肽水凝胶作为可注射递送系统,以控制方式在梗死区域内封装和释放miR-181a安塔戈莫。通过掺入不同的β-高赖氨酸残基来合成β-肽,以调节与核酸的静电相互作用。所得水凝胶表现出剪切变薄和自愈特性,在脑组织的生理范围内的刚度值和可调的核酸释放谱延长超过3周。在小鼠光血栓性中风后,脑内注射装有安他哥米的水凝胶实现了精确的梗死递送,并持续存在至少7天。尽管梗死面积减少幅度不大,但与对照组相比,水凝胶-安他戈米尔组的功能恢复(通过吊丝试验中运动协调性的改善来衡量)明显增强。这些发现突出了β-肽水凝胶作为有前途的平台,用于核酸治疗的局部持续递送。这项工作建立了脑卒中中水凝胶介导的miRNA传递的概念验证,并为进一步优化临床相关模型提供了基础。
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引用次数: 0
Superparamagnetic Fe3O4 nanoclusters for cancer therapy and metastasis prevention via synergistic chemotherapy and NETs degradation 超顺磁性Fe3O4纳米团簇通过协同化疗和NETs降解治疗癌症和预防转移。
IF 6 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2026-01-07 DOI: 10.1016/j.bioadv.2026.214709
Liqin Xie , Tianyi Zeng , Dan Li , Wenke Chang , Shenglu Ji , Zichun Hua
The overexpression of neutrophil extracellular traps (NETs) serves as a critical biomarker and mediator of tumorigenesis and metastasis. By inhibiting their formation or degrading existing structures, therapeutic strategies targeting NETs have shown promising potential in cancer treatment and metastasis prevention. Deoxyribonuclease I (DNase), while effective in NETs degradation, suffers from rapid plasma clearance, necessitating delivery vehicles to prolong its therapeutic activity. In this study, we developed superparamagnetic Fe3O4 nanoclusters via a one-step solvothermal method for co-delivery of doxorubicin (DOX) and DNase. The resulting nanoplatform demonstrated: (1) enhanced magnetic retention at tumor sites for improved local drug concentration and targeted delivery, and (2) synergistic therapeutic effects under alternating magnetic field (AMF) exposure, combining magnetic hyperthermia with chemotherapy while simultaneously remodeling the tumor microenvironment through NETs degradation. Comprehensive evaluations revealed that this combined approach significantly enhanced antitumor efficacy compared to monotherapies, with the additional benefit of metastasis prevention through tumor microenvironment modulation. This multifunctional nanoplatform thus represents a promising strategy for synergistic cancer therapy, addressing both primary tumor control and metastatic suppression.
中性粒细胞胞外陷阱(NETs)的过度表达是肿瘤发生和转移的关键生物标志物和中介。通过抑制其形成或降解现有结构,靶向NETs的治疗策略在癌症治疗和预防转移方面显示出良好的潜力。脱氧核糖核酸酶I (DNase)虽然对NETs降解有效,但血浆清除速度很快,因此需要递送载体来延长其治疗活性。在这项研究中,我们通过一步溶剂热法开发了超顺磁性的Fe3O4纳米团簇,用于共同递送阿霉素(DOX)和dna酶。由此产生的纳米平台证明:(1)增强了肿瘤部位的磁保留,提高了局部药物浓度和靶向递送;(2)在交变磁场(AMF)暴露下的协同治疗效果,将磁热疗与化疗结合起来,同时通过NETs降解重塑肿瘤微环境。综合评价显示,与单一疗法相比,这种联合疗法显著提高了抗肿瘤疗效,并通过调节肿瘤微环境预防转移。因此,这种多功能纳米平台代表了一种很有前途的协同癌症治疗策略,既能控制原发肿瘤,又能抑制转移性肿瘤。
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Materials Science & Engineering C-Materials for Biological Applications
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