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Adipose-Derived Stem Cell-Loaded Fish-GelMA/CMC Hydrogel Accelerates Wound Healing via Macrophage Polarization Suppression and Promoting Angiogenesis 脂肪来源干细胞装载的Fish-GelMA/CMC水凝胶通过抑制巨噬细胞极化和促进血管生成加速伤口愈合。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-28 DOI: 10.1002/jbm.a.38008
Xue Xue, Han Xue, Rong Lu, Jiahao Ji

Extensive cutaneous injuries with impaired regenerative capacity present substantial risks to both public health and socioeconomic systems. Current skin substitutes remain inadequate in fully replicating native tissue architecture and physiological functionality. While fish skin-derived gelatin-methacrylate (F-GelMA) serves as a principal scaffold material in vitro skin models, it has weak mechanical properties and limited mechanical strength, which necessitates supplementation with viscosity-enhancing additives. We created functional in vitro 3D extracellular matrix mimics with composite hydrogels based on F-GelMA and the thickener carboxymethyl cellulose (CMC). The physicochemical properties and bioactivity of the hydrogel scaffolds were assessed through testing their rheological properties, swelling behavior, degradation characteristics, and biocompatibility. It was discovered that the F-GelMA/CMC hydrogel bioscaffold loaded with adipose-derived stem cells (ADSCs) expedited wound healing by facilitating wound re-epithelialization, enhancing wound collagen formation, accelerating the deposition of myofibroblasts at the wound site, promoting angiogenesis, stimulating the proliferation and differentiation of keratinocytes, and suppressing skin wound inflammation.

大面积皮肤损伤伴再生能力受损,对公共卫生和社会经济系统构成重大风险。目前的皮肤替代品在完全复制天然组织结构和生理功能方面仍然不足。虽然鱼皮衍生明胶-甲基丙烯酸酯(F-GelMA)作为体外皮肤模型的主要支架材料,但它具有较弱的机械性能和有限的机械强度,这需要补充粘度增强添加剂。我们用基于F-GelMA和增稠剂羧甲基纤维素(CMC)的复合水凝胶构建了体外三维细胞外基质模拟物。通过测试水凝胶支架的流变性能、溶胀特性、降解特性和生物相容性来评价其理化性能和生物活性。研究发现,装载脂肪源性干细胞(ADSCs)的F-GelMA/CMC水凝胶生物支架通过促进创面再上皮化、促进创面胶原形成、加速肌成纤维细胞在创面部位的沉积、促进血管生成、刺激角质形成细胞的增殖和分化、抑制皮肤创面炎症来加速创面愈合。
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引用次数: 0
Flavonoid-Enriched Solanum mauritianum Leaf Extract/PU/PCL Composite Attenuates Ang II-Induced Inflammation in Cardiomyocytes and Enhances Cell Adhesion 富黄酮类化合物龙葵叶提取物/PU/PCL复合物可减轻angii诱导的心肌细胞炎症并增强细胞粘附。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-27 DOI: 10.1002/jbm.a.38009
Aswathy Karanath-Anilkumar, Muhammad Sadiq, Suganya Ganesan, Neeraja Bose, Kalaivizhi Rajappan, Ganesh Munuswamy-Ramanujam

Inflammatory disorders like cardiovascular diseases remain a major global health concern, with oxidative stress and chronic inflammation playing critical roles in disease progression. This study presents a PU/PCL composite functionalized with flavonoid-enriched Solanum mauritianum leaf extract (SL). Incorporation of SL into PU/PCL enhanced its hydrophilicity, oxidative stability, and anti-inflammatory properties, while enabling sustained drug release without adverse in vitro toxicity. PU/PCL/SL was fabricated using a phase inversion technique and characterized to confirm strong molecular interactions, improved thermal stability, and a porous structure that facilitated controlled release. The composite exhibited potent antioxidant and anti-inflammatory activity. PU/PCL/SL showed biocompatibility to H9c2 cardiomyocytes and Peripheral Blood Mononuclear Cells, while confocal imaging demonstrated enhanced cellular adhesion of H9c2 to PU/PCL/SL. Flow cytometry confirmed the ability of the biomaterial to reduce intracellular ROS. PU/PCL/SL was able to significantly downregulate TNF-α, IL-6, IL-1β, and TLR4 in AngII-activated cardiomyocytes. This highlighted the material's potential as an immunomodulator that can target inflammation. Collectively, these results demonstrate the successful fabrication of a flavonoid-functionalized PU/PCL composite with improved physicochemical properties, sustained release capability, and strong biological relevance through biocompatibility and immunomodulatory activity. Together, these findings position PU/PCL/SL as an advanced multifunctional biomaterial with promising applications in cardiovascular disease.

炎症性疾病如心血管疾病仍然是一个主要的全球健康问题,氧化应激和慢性炎症在疾病进展中起着关键作用。研究了以富黄酮类化合物龙葵叶提取物(SL)为功能化剂的PU/PCL复合材料。将SL掺入PU/PCL中,增强了其亲水性、氧化稳定性和抗炎性能,同时使药物持续释放,无不良的体外毒性。PU/PCL/SL采用相转化技术制备,并对其进行了表征,证实了强分子相互作用、改善的热稳定性和有利于控释的多孔结构。该复合物具有较强的抗氧化和抗炎活性。PU/PCL/SL对H9c2心肌细胞和外周血单核细胞表现出生物相容性,共聚焦成像显示PU/PCL/SL对H9c2的细胞粘附增强。流式细胞术证实了生物材料减少细胞内ROS的能力。PU/PCL/SL能够显著下调血管活化心肌细胞中的TNF-α、IL-6、IL-1β和TLR4。这凸显了这种材料作为免疫调节剂的潜力,可以靶向炎症。综上所述,这些结果证明了成功制备的类黄酮功能化PU/PCL复合材料具有更好的物理化学性能、缓释能力,并通过生物相容性和免疫调节活性具有很强的生物学相关性。总之,这些发现表明PU/PCL/SL是一种先进的多功能生物材料,在心血管疾病中具有广阔的应用前景。
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引用次数: 0
Silver (I) and Silver (II) Oxide Films for Biomedical Implants: Synthesis, Stability, Ion Release, and Antibacterial Efficacy 用于生物医学植入物的银(I)和银(II)氧化物薄膜:合成、稳定性、离子释放和抗菌功效。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-27 DOI: 10.1002/jbm.a.38006
Maxwell Akantibila, Hailey Maurer, Matthew Urban, Steven DiSpirito, John Torres, Arwa Muhamed, Janiyah Harris, Alex Bharath, Roxanne Green, Theodore H. Scabarozi, Gregory A. Caputo, Valerie J. Carabetta, Jeffrey D. Hettinger

Coatings of silver compounds with higher dissolution rates than metallic silver offer a promising approach for delivering Ag+ ions to prevent medical implant device-associated infections. In this study, we investigate the synthesis and characterization of single-phase, silver (I) oxide (Ag2O) and silver (II) oxide (AgO) for potential antimicrobial applications. The synthesis of these materials leverages the higher stability of Ag2O in comparison to AgO. The formation of AgO requires a low landing energy of the adatoms, achieved through gas phase scattering and rapid quenching when landing. Alternatively, higher landing energies cause re-sputtering of oxygen, which favors the formation of Ag2O. Higher chamber pressures during deposition increase the number of inelastic collisions, thereby reducing the energy of the adatoms influencing phase formation. A combination of energy dispersive spectroscopy, microstructural imaging, X-ray diffraction (XRD), and high-temperature XRD confirms this result. To evaluate antimicrobial potential, silver ion release (elution) was measured in water, Luria-Bertani broth, and tryptic soy broth. Elution rates were highest in water, but in all media, both oxides elute significantly more Ag+ ions than metallic silver coatings. Antimicrobial assays clearly show potent and broad-spectrum activity of silver oxides against both clinical and multidrug-resistant bacteria, confirming their potential as effective antimicrobial coatings for implanted devices.

银化合物涂层具有比金属银更高的溶解速率,为递送银离子以防止医疗植入装置相关感染提供了一种有前途的方法。在这项研究中,我们研究了单相氧化银(Ag2O)和氧化银(AgO)的合成和表征。与AgO相比,这些材料的合成利用了Ag2O更高的稳定性。AgO的形成需要附着原子的低着陆能量,这是通过气相散射和着陆时的快速淬火来实现的。或者,更高的着陆能量导致氧的重新溅射,这有利于Ag2O的形成。在沉积过程中,较高的腔室压力增加了非弹性碰撞的次数,从而降低了影响相形成的附原子的能量。能量色散光谱、显微结构成像、x射线衍射(XRD)和高温x射线衍射(XRD)的结合证实了这一结果。为了评价抗菌潜力,测定了水、Luria-Bertani肉汤和胰蛋白酶豆汤中银离子的释放(洗脱)。在水中的洗脱率最高,但在所有介质中,两种氧化物洗脱的Ag+离子明显多于金属银涂层。抗菌试验清楚地显示出氧化银对临床和多药耐药细菌的有效和广谱活性,证实了其作为植入装置有效抗菌涂层的潜力。
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引用次数: 0
Characterizing Piezoelectric-Blended Polydimethylsiloxane for Use as a Mechanoelectrical Responsive Cell Culture Substrate 压电混合聚二甲基硅氧烷作为机械电反应细胞培养基质的表征。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-23 DOI: 10.1002/jbm.a.38002
Alexis P. Applequist, Lance D. Cordes, Laís A. Ferreira, Kartik Balachandran

In this study, we developed a piezoelectric-polydimethylsiloxane (pz-PDMS) composite by blending poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) with PDMS to create a biocompatible, mechanoelectrical responsive material. The pz-PDMS was synthesized with varying piezoelectric concentrations (0%, 1%, 3%, and 5%) and characterized for visual properties, mechanical properties, mechanoelectrical sensitivity, and biocompatibility. Compression testing showed no significant change in mechanical strength with the addition of piezoelectric particles, while mechanolectrical sensitivity testing revealed a non-linear increase in voltage response, with 5% pz-PDMS producing the highest sensitivity. Fatigue testing demonstrated no change in sensitivity after 7 days of cyclic displacement. Additionally, microcantilever experiments demonstrated the high fidelity of the 5% pz-PDMS to mechanical deformation. In parallel, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes cultured on both 0% pz-PDMS and 5% pz-PDMS substrates exhibited comparable cell viability, attachment, and maturation, as confirmed by MTS assays and immunofluorescence imaging. The results suggest that 5% pz-PDMS offers a promising platform for bioelectronic applications, combining piezoelectric functionality with long-term biocompatibility.

在这项研究中,我们通过将聚偏氟乙烯-共三氟乙烯(P(VDF-TrFE))与PDMS混合,开发了一种压电-聚二甲基硅氧烷(pz-PDMS)复合材料,以创造一种生物相容性的机电响应材料。pz-PDMS以不同的压电浓度(0%、1%、3%和5%)合成,并对其视觉性能、机械性能、机电灵敏度和生物相容性进行了表征。压缩测试显示,压电颗粒的加入对机械强度没有显著影响,而机电灵敏度测试显示,电压响应呈非线性增加,5% pz-PDMS产生最高灵敏度。疲劳试验表明,经过7天的循环位移后,敏感性没有变化。此外,微悬臂实验证明了5% pz-PDMS对机械变形的高保真度。同时,MTS实验和免疫荧光成像证实,在0% pz-PDMS和5% pz-PDMS基质上培养的人诱导多能干细胞(hiPSC)来源的心肌细胞表现出相似的细胞活力、附着和成熟。结果表明,5% pz-PDMS结合了压电功能和长期生物相容性,为生物电子应用提供了一个很有前景的平台。
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引用次数: 0
Exogenous Extracellular Matrix in an Environmentally-Mediated In Vitro Model for Cardiac Fibrosis 外源性细胞外基质在环境介导的心脏纤维化体外模型中的应用。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-23 DOI: 10.1002/jbm.a.37994
Natalie Pachter, Kristen Allen, Tracy A. Hookway

Few clinical solutions exist for cardiac fibrosis, creating the need for a tunable in vitro model to better understand fibrotic disease mechanisms and screen potential therapeutic compounds. Here, we combined cardiomyocytes, cardiac fibroblasts, and exogenous extracellular matrix (ECM) proteins to create an environmentally mediated in vitro cardiac fibrosis model. Cells and ECM were combined into 2 types of cardiac tissues—aggregates and tissue rings. The addition of collagen I had a drastic negative impact on aggregate formation, but ring formation was not as drastically affected. In both tissue types, collagen and other ECM did not severely affect contractile function. Histological analysis showed direct incorporation of collagen into tissues, indicating that we can directly modulate the cells' ECM environment. This modulation affects tissue formation and distribution of cells, indicating that this model provides a useful platform for understanding how cells respond to changes in their extracellular environment and for potential therapeutic screening.

针对心脏纤维化的临床解决方案很少,因此需要一种可调节的体外模型来更好地了解纤维化疾病的机制并筛选潜在的治疗化合物。在这里,我们将心肌细胞、心脏成纤维细胞和外源性细胞外基质(ECM)蛋白结合在一起,创建了一个环境介导的体外心脏纤维化模型。细胞与ECM结合形成聚集体和组织环2种类型的心脏组织。胶原蛋白I的添加对聚集体的形成有明显的负面影响,但对环的形成没有明显的影响。在两种组织类型中,胶原蛋白和其他ECM均未严重影响收缩功能。组织学分析显示胶原蛋白直接进入组织,表明我们可以直接调节细胞的ECM环境。这种调节影响组织形成和细胞分布,表明该模型为理解细胞如何响应细胞外环境的变化和潜在的治疗筛选提供了一个有用的平台。
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引用次数: 0
In Vitro Oxidative Degradation of Hydroxyapatite Biopolymer Nanocomposites and the Resulting Consequences on Their Mechanical Performance 羟基磷灰石生物聚合物纳米复合材料的体外氧化降解及其对力学性能的影响。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-23 DOI: 10.1002/jbm.a.38003
Elizabeth V. Diederichs, Dibakar Mondal, Thomas L. Willett

Development of synthetic biomaterials for skeletal reconstruction has progressed rapidly, driven partly by demand to reduce dependency on allografts. One class of materials, biopolymer nanocomposites, has shown promise when combined with additive manufacturing for these applications. The driving goal for the development of 3D-printable biopolymer nanocomposites composed of methacrylated monomers (triglycerides and triethylene glycol) and hydroxyapatite (HA) is to produce structurally robust and degradable customizable grafts. These materials must be able to withstand the loading conditions found in vivo while allowing for degradation and remodeling processes. This study focused on the degradation potential of previously developed HA-containing biopolymer nanocomposites and the resulting consequences of degradation on their mechanical performance. One of the means to study a material's in vivo degradation performance is to assess its susceptibility to oxidative degradation, as oxidation is naturally occurring in cell metabolism, inflammatory responses, and osteoclast resorption. Two in vitro models of oxidative degradation were trialed: aqueous solutions of either hydrogen peroxide or neutral hypochlorous acid. Hypochlorous acid was shown to be a useful in vitro assessment for the degradation potential of biomaterials to different reactive oxygen species. The biopolymer nanocomposites were clearly susceptible to oxidative degradation, demonstrating significant changes in mass and surface morphology. Mechanical performance was reduced under these testing conditions. This was attributed to three main factors: swelling and water absorption effects, chemical modifications, and loss of structure. Overall, this study provides insights into the effects of oxidative degradation on biomaterial functionality and highlights the importance of exploring relevant physiological effects on mechanical properties when developing biomaterials.

用于骨骼重建的合成生物材料的发展进展迅速,部分原因是需求减少对同种异体移植物的依赖。一类材料,生物聚合物纳米复合材料,在与增材制造相结合的情况下,显示出了应用前景。由甲基丙烯酸酯单体(甘油三酯和三甘醇)和羟基磷灰石(HA)组成的3d打印生物聚合物纳米复合材料的发展驱动目标是生产结构坚固且可降解的定制接枝。这些材料必须能够承受在体内发现的加载条件,同时允许降解和重塑过程。本研究的重点是先前开发的含ha生物聚合物纳米复合材料的降解潜力,以及降解对其机械性能的影响。研究材料在体内降解性能的方法之一是评估其对氧化降解的易感性,因为氧化在细胞代谢、炎症反应和破骨细胞吸收中自然发生。两种体外氧化降解模型进行了试验:过氧化氢水溶液或中性次氯酸水溶液。次氯酸被证明是一个有用的体外评估生物材料对不同活性氧的降解潜力。生物聚合物纳米复合材料明显易受氧化降解,表现出质量和表面形貌的显著变化。在这些测试条件下,机械性能降低。这主要归因于三个因素:膨胀和吸水效应、化学修饰和结构损失。总的来说,这项研究提供了氧化降解对生物材料功能的影响的见解,并强调了在开发生物材料时探索相关生理效应对机械性能的重要性。
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引用次数: 0
Dynamic Loading Does Not Interfere With the Initial Repopulation of Decellularized Tendons: An Ex Vivo Study 动态载荷不影响脱细胞肌腱的初始再生:一项离体研究。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-14 DOI: 10.1002/jbm.a.38005
Janne Spierings, Florencia Abinzano, Elias Salzer, Jurgen Bulsink, Rob Janssen, Keita Ito, Jasper Foolen

Rupture of the anterior cruciate ligament (ACL) is a common injury resulting in joint instability. Tendon autografts, the gold standard to reconstruct a ruptured ACL, contain dead or dying cells upon implantation that can initiate early localized catabolic and inflammatory events. This is hypothesized to contribute to detrimental remodeling, which may compromise graft stability and increase the risk of rupture. To address this, we propose using decellularized grafts. However, the cells used to reseed decellularized tendons cannot be detected anymore in vivo, potentially due to the dynamic loading conditions. Therefore, the repopulation efficiency of decellularized tendons under dynamic load was investigated using a custom developed bioreactor. As a proof of concept, human gracilis tendons were decellularized and reseeded with human dermal fibroblasts and cultured for 7 days dynamically (2%–6% strain at 1 Hz for 7 h a day) or statically. Thereafter, the viability and infiltration ability of the reseeded cells were assessed. The loading protocol used in this study demonstrated that the bioreactor could measure the transient response of tendon mechanical behavior and could detect changes in mechanical properties over time. The application of dynamic load to reseeded decellularized tendons had no significant effect on cell adhesion, viability, cell metabolism, and infiltration. In both loading groups, cell infiltration was localized rather than globally observed. As bioreactors can serve as an in vitro or ex vivo model to potentially predict in vivo outcomes, this bioreactor shows promising potential for future ACL graft research.

前交叉韧带(ACL)断裂是一种常见的损伤导致关节不稳定。自体肌腱移植是重建断裂前交叉韧带的金标准,在植入时含有死亡或垂死的细胞,可引发早期局部分解代谢和炎症事件。据推测,这可能会导致有害的重塑,从而损害移植物的稳定性并增加破裂的风险。为了解决这个问题,我们建议使用脱细胞移植物。然而,可能由于动态加载条件的原因,体内无法再检测到用于再播种脱细胞肌腱的细胞。因此,采用自行开发的生物反应器研究了动态载荷下脱细胞肌腱的再生效率。为了证明这一概念,我们将人股薄肌腱脱细胞,用人皮肤成纤维细胞重新播种,并动态培养7天(2%-6%的应变,1 Hz,每天7小时)或静态培养7天。然后,评估再播种细胞的活力和浸润能力。本研究中使用的加载方案表明,生物反应器可以测量肌腱力学行为的瞬态响应,并可以检测力学性能随时间的变化。动态负荷对再播种脱细胞肌腱的细胞粘附、活力、细胞代谢和浸润均无显著影响。在两个加载组中,细胞浸润都是局部的,而不是全局的。由于生物反应器可以作为体外或离体模型来潜在地预测体内结果,因此该生物反应器在未来的ACL移植物研究中显示出良好的潜力。
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引用次数: 0
Electro-Actuation of a Smart Hydrogel Compatible With 3D Printing 与3D打印兼容的智能水凝胶的电动驱动。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-14 DOI: 10.1002/jbm.a.38004
Georgios Mikalef, Zoe Schofield, Samuel Robert Moxon, Thomas Edward Robinson, Hin On Chu, Peter Freddie Nugent, Daniele Baiocco, Patricia Perez Esteban, Liam Michael Grover

Hydrogels that can change shape on the application of an electric field are receiving increasing attention due to their potential to fulfill a range of functions in biomedicine, including the controlled release of therapeutic agents or the creation of replacements for contractile tissues. In this manuscript, a novel electroactive polymer was reported based on the copolymerisation of 2-acrylamido-2-methylpronane sulfonic acid and poly(ethylene glycol) diacrylate (AMPS-co-PEGDA), via free radical polymerization using UV light. It was shown that to enable curing and the production of a material that could repeatably actuate without cracking, 900 mJ/cm2 (at 365 nm−1) of UV exposure was optimal. Further increasing the curing time resulted in the production of a brittle material that cracked following actuation, preventing multiple actuations from occurring. The polymer that was cured for 900 mJ/cm2 was shown to be non-cytotoxic to dermal fibroblast cells, showing potential in biomedical applications. Furthermore, it was shown that the optimized polymer could be structured using a process of suspended 3D printing, allowing for the manufacture of complex, electro-actuatable geometries. Processing in an agarose supporting bed resulted in a reduction in the Young's modulus of the printed polymer and an associated greater degree of bending. These results demonstrate that the optimized (AMPS-co-PEGDA) polymer is a promising electroactive material with tuneable properties and complex geometries, suitable for advanced biomedical applications.

在电场作用下可以改变形状的水凝胶正受到越来越多的关注,因为它们在生物医学中具有实现一系列功能的潜力,包括控制治疗剂的释放或创造可收缩组织的替代品。本文报道了一种基于2-丙烯酰胺-2-甲基丙烷磺酸和聚乙二醇二丙烯酸酯(AMPS-co-PEGDA)的紫外自由基聚合的新型电活性聚合物。研究表明,为了使固化和生产一种可以重复驱动而不开裂的材料,900 mJ/cm2 (365 nm-1)的紫外线照射是最佳的。进一步增加固化时间导致脆性材料的产生,在驱动后开裂,防止多次驱动的发生。经900 mJ/cm2固化的聚合物对真皮成纤维细胞无细胞毒性,具有生物医学应用潜力。此外,研究表明,优化后的聚合物可以使用悬浮3D打印工艺进行构建,从而可以制造复杂的、可电致动的几何形状。在琼脂糖支撑床中处理导致打印聚合物的杨氏模量降低,并导致更大程度的弯曲。这些结果表明,优化后的(AMPS-co-PEGDA)聚合物是一种有前途的电活性材料,具有可调谐的性能和复杂的几何形状,适合先进的生物医学应用。
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引用次数: 0
In Vitro Assessment and Preliminary In Vivo Characterization of Innovative Hybrid Materials for Biomedical Applications 生物医学应用的新型混合材料的体外评估和初步体内表征。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-10 DOI: 10.1002/jbm.a.37959
Martina Todesco, Roberto Luisetto, Martina Casarin, Edi Simoni, Diego Penzo, Deborah Sandrin, Michele Modesti, Laura Astolfi, Giovanna Albertin, Filippo Romanato, Massimo Marchesan, Gino Gerosa, Chiara Giulia Fontanella, Andrea Bagno

Hybrid materials are gaining increasing attention for several applications since they properly combine biological and synthetic components, leveraging the advantages of both; thus, these materials can integrate with the host organism to support proper functions, offering new promising solutions, especially in the biomedical field. In this study, we developed hybrid membranes by combining decellularized porcine pericardium with a commercial polycarbonate urethane, available in two formulations: without (AR) and with microsilica particles (AR-LT). These membranes were characterized through chemical and physical analyses; their cytocompatibility was assessed in vitro via direct contact tests, and their biocompatibility was checked in vivo by implanting the materials in a subdermal pouch in a rat animal model. Three kinds of mechanical tests have been performed to check different mechanical features: tensile test to rupture, to measure the mechanical resistance in terms of elastic modulus, failure strain (FS), and ultimate tensile strength (UTS); cyclic tests to assess the effects of repetitive loadings on the mechanical resistance; and stress-relaxation tests to assess the time-dependent behavior. The physicochemical analyses demonstrated that the two components well adhere to each other, with traces of the polymer on the pericardial side of the membranes. Considering mechanical response, coupling pericardium with the polymer causes a reduction of FS and UTS compared to the individual components. Hybrid materials show a viscoelastic behavior while loading cycles do not cause significant changes in their tensile resistance. In vitro tests showed no cytotoxic effects, with cell proliferation observed for up to 7 days. In vivo, 8 weeks after implantation, the hybrid membranes exhibited better integration with host tissue compared to the polymer alone (control), and the polymeric component did not show any sign of degradation. The improved integration was demonstrated by increased neovascularization around the implant, reduced fibrotic capsule thickness, lower expression of interleukin-6 (IL-6), and stable body weight of the rats throughout the experiment. This study highlights the potential of the hybrid membranes for tissue engineering applications, combining favorable biocompatibility and adequate mechanical features.

混合材料在一些应用中越来越受到关注,因为它们适当地结合了生物和合成成分,充分利用了两者的优势;因此,这些材料可以与宿主生物结合以支持适当的功能,提供了新的有前途的解决方案,特别是在生物医学领域。在这项研究中,我们通过将脱细胞猪心包与商业聚碳酸酯氨基甲酸酯结合,开发了杂交膜,有两种配方:不含(AR)和含有微二氧化硅颗粒(AR- lt)。通过化学和物理分析对这些膜进行了表征;在体外通过直接接触试验评估了它们的细胞相容性,在体内通过植入大鼠动物模型的皮下袋来检查它们的生物相容性。为了检验不同的力学特性,进行了三种力学试验:拉伸断裂试验,以弹性模量、破坏应变(FS)和极限抗拉强度(UTS)来测量机械阻力;循环试验,评估重复载荷对机械阻力的影响;以及压力放松测试来评估时间依赖性行为。物理化学分析表明,这两种成分相互粘附良好,在膜的心包一侧有聚合物的痕迹。考虑到机械响应,与单个组件相比,心包与聚合物的耦合导致FS和UTS的降低。混合材料表现出粘弹性行为,而加载循环不会引起其抗拉性能的显著变化。体外试验显示无细胞毒性作用,细胞增殖观察长达7天。在体内,植入8周后,与单独的聚合物(对照组)相比,杂交膜与宿主组织的结合更好,聚合物成分没有出现任何降解迹象。在整个实验过程中,植入物周围的新生血管增加,纤维化囊厚度减少,白细胞介素-6 (IL-6)的表达降低,大鼠的体重稳定,证明了这种改善的整合。这项研究强调了混合膜在组织工程应用中的潜力,结合了良好的生物相容性和充分的机械特性。
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引用次数: 0
Modulating Hydrogel Stiffness Through Light-Based 3D Printing to Mimic Cardiac Fibrosis and Cardiomyocyte Dysfunction Using hiPSC-Derived Cells 利用hipsc衍生细胞通过光基3D打印模拟心脏纤维化和心肌细胞功能障碍来调节水凝胶硬度。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-10-07 DOI: 10.1002/jbm.a.37997
Sogu Sohn, Nima Momtahan, Lynn M. Stevens, Jiwan Han, Yutong Liu, Meghan T. Kiker, Elizabeth A. Recker, Zachariah A. Page, Janet Zoldan

The human heart's limited regenerative capacity is a significant barrier to addressing cardiovascular disease (CVD). This is particularly true for cardiac fibrosis, a form of CVD wherein the wound healing process has gone awry. In cardiac fibrosis, excessive scar tissue formation due to dysregulated remodeling of the heart's extracellular matrix (ECM) results in increased stiffness that reduces cardiac output and can lead to heart failure. This dysregulated ECM deposition is driven by activated cardiac fibroblasts, where cell substrate stiffness is known to play a role in cardiac fibroblast activation. New preclinical models that accurately recapitulate the behavior of activated cardiac fibroblasts are needed to better understand and treat cardiac fibrosis. To this end, we describe a model wherein human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts (HCFs) are cultured on 3D printed hydrogels of tunable stiffness, fabricated using dosage-controlled digital light processing (DLP). We demonstrate that our model can induce HCF activation in the absence of TGFβ, a key mediator of fibroblast activation, surpassing the activation levels seen with HCFs activated with TGFβ on protein-coated tissue culture plates. Furthermore, combining stiffer hydrogels with TGFβ recapitulates fibroblast activation similar to what is observed in native cardiac tissue. Lastly, by indirectly coculturing HCFs seeded and activated on these stiff hydrogels with hiPSC-derived cardiomyocytes, we demonstrate that the activated HCFs in our cardiac fibrosis model can impair cardiomyocyte function, mimicking the deleterious effects of cardiac fibrosis.

人类心脏有限的再生能力是解决心血管疾病(CVD)的重要障碍。对于心脏纤维化来说尤其如此,这是一种CVD,其中伤口愈合过程已经出错。在心脏纤维化中,由于心脏细胞外基质(ECM)重塑失调导致的过度瘢痕组织形成导致硬度增加,减少心输出量并导致心力衰竭。这种失调的ECM沉积是由活化的心脏成纤维细胞驱动的,其中细胞底物硬度已知在心脏成纤维细胞活化中起作用。为了更好地理解和治疗心脏纤维化,需要新的临床前模型准确地概括活化的心脏成纤维细胞的行为。为此,我们描述了一个模型,其中人类诱导多能干细胞(hiPSC)衍生的心脏成纤维细胞(hcf)在可调刚度的3D打印水凝胶上培养,使用剂量控制的数字光处理(DLP)制造。我们证明,我们的模型可以在没有tgf - β的情况下诱导HCF激活,tgf - β是成纤维细胞激活的关键介质,超过了在蛋白包被的组织培养板上用tgf - β激活的HCF的激活水平。此外,将更硬的水凝胶与TGFβ结合可以重现成纤维细胞的活化,类似于在天然心脏组织中观察到的情况。最后,通过间接地将HCFs与hipsc衍生的心肌细胞共培养,我们证明,在我们的心脏纤维化模型中,激活的HCFs可以损害心肌细胞功能,模拟心脏纤维化的有害影响。
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Journal of biomedical materials research. Part A
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