首页 > 最新文献

Journal of biomedical materials research. Part A最新文献

英文 中文
Injectable Nano-Micron AKBA Delivery Platform for Treatment of Tendinopathy in a Rat Model 纳米微米AKBA注射给药平台治疗大鼠肌腱病变模型。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-13 DOI: 10.1002/jbm.a.37844
Qibin Han, Yinhua Qian, Lang Bai, Jing Zhou, Yuefeng Hao, Dan Hu, Zhouzhou Zhang, Xing Yang

Tendinopathy is a disorder characterized by pain and reduced function due to a series of changes in injured or diseased tendons. Inflammation and collagen degeneration are key contributors to the onset and chronic nature of tendinopathy. Acetyl-11-keto-β-boswellic acid (AKBA) is an effective anti-inflammatory agent widely used in chronic inflammatory disorders and holds potential for tendinopathy treatment; however, its therapeutic efficacy is limited by poor aqueous solubility. Here, we fabricated AKBA-encapsulated cationic liposome-gelatin methacrylamide (GelMA) microspheres (GM-Lipo-AKBA) using thin-film hydration and microfluidic technology for drug delivery therapy. GM-Lipo-AKBA exhibited high encapsulation efficiency, extended AKBA release for over 4 weeks, and prolonged degradation. In vitro and in vivo experiments demonstrated its effectiveness in improving inflammation and ECM remodeling in tendinopathy. In summary, the injectable nano-micron drug delivery platform provides a promising strategy for the sustained and localized delivery of AKBA for tendinopathy treatment.

肌腱病是一种因受伤或患病肌腱发生一系列变化而导致疼痛和功能减退的疾病。炎症和胶原蛋白变性是导致肌腱病发病和慢性化的主要原因。乙酰基-11-酮-β-乳香酸(AKBA)是一种有效的抗炎药物,被广泛用于慢性炎症性疾病的治疗,并具有治疗肌腱病的潜力;然而,由于其水溶性较差,其疗效受到了限制。在此,我们利用薄膜水合和微流控技术制备了阳离子脂质体-明胶甲基丙烯酰胺(Gelatin methacrylamide,GelMA)包封微球(GM-Lipo-AKBA),用于给药治疗。GM-Lipo-AKBA 具有封装效率高、AKBA 释放时间长达 4 周以上、降解时间长等特点。体外和体内实验证明,它能有效改善肌腱病的炎症和 ECM 重塑。总之,这种可注射的纳米微米给药平台为 AKBA 持续、局部给药治疗肌腱病提供了一种前景广阔的策略。
{"title":"Injectable Nano-Micron AKBA Delivery Platform for Treatment of Tendinopathy in a Rat Model","authors":"Qibin Han,&nbsp;Yinhua Qian,&nbsp;Lang Bai,&nbsp;Jing Zhou,&nbsp;Yuefeng Hao,&nbsp;Dan Hu,&nbsp;Zhouzhou Zhang,&nbsp;Xing Yang","doi":"10.1002/jbm.a.37844","DOIUrl":"10.1002/jbm.a.37844","url":null,"abstract":"<div>\u0000 \u0000 <p>Tendinopathy is a disorder characterized by pain and reduced function due to a series of changes in injured or diseased tendons. Inflammation and collagen degeneration are key contributors to the onset and chronic nature of tendinopathy. Acetyl-11-keto-β-boswellic acid (AKBA) is an effective anti-inflammatory agent widely used in chronic inflammatory disorders and holds potential for tendinopathy treatment; however, its therapeutic efficacy is limited by poor aqueous solubility. Here, we fabricated AKBA-encapsulated cationic liposome-gelatin methacrylamide (GelMA) microspheres (GM-Lipo-AKBA) using thin-film hydration and microfluidic technology for drug delivery therapy. GM-Lipo-AKBA exhibited high encapsulation efficiency, extended AKBA release for over 4 weeks, and prolonged degradation. In vitro and in vivo experiments demonstrated its effectiveness in improving inflammation and ECM remodeling in tendinopathy. In summary, the injectable nano-micron drug delivery platform provides a promising strategy for the sustained and localized delivery of AKBA for tendinopathy treatment.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Gamma Irradiation on Structural, Chemical, Bioactivity and Biocompatibility Characteristics of Bioactive Glass–Polymer Composite Film γ辐照对生物活性玻璃-聚合物复合膜结构、化学、生物活性及生物相容性的影响
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-13 DOI: 10.1002/jbm.a.37842
Mamun Khan Sujon, Siti Fatimah Samsurrijal, Ruzalina Baharin, Naurah Mat Isa, Muhammad Azrul Zabidi, Siti Noor Fazliah Mohd Noor

Gamma irradiation is an effective technique for biocomposite films intended for application in tissue engineering (TE) to ensure sterility and patient safety prior to clinical applications. This study proposed a biocomposite film composed of natural polymer chitosan (CS) and synthetic polymer poly-Ɛ-caprolactone (PCL) reinforced with sol–gel-derived bioactive glass (BG) for potential application in TE. The BG/PCL/CS biocomposite film was sterilized using 25 kGy gamma rays, and subsequent changes in its characteristics were analyzed through mechanical and physical assessment, bioactivity evaluation via immersion in simulated body fluid (SBF) and biocompatibility examination using human primary dermal fibroblasts (HPDFs). Results indicated a homogeneous distribution of BG particles within the BG/PCL/CS polymer matrix which enhanced bioactivity, and the polymer blend provide a structurally stable film. Gamma irradiation induced an increase in the film's surface roughness due to photo-oxidative degradation; however, this did not adversely affect the integrity of glass particles and polymer chains. In vitro assessments demonstrated hydroxyapatite formation on the film's surface, suggesting bioactivity. Biocompatibility testing confirmed enhanced cell adhesion and proliferation. These multifunctional properties highlight the potential of the fabricated BG/PCL/CS biocomposite film for TE and regenerative medicine applications.

伽马辐照是应用于组织工程(TE)的生物复合膜的有效技术,可确保临床应用前的无菌性和患者安全。本研究提出了一种由天然聚合物壳聚糖(CS)和合成聚合物聚己内酯(PCL)以及溶胶凝胶衍生生物活性玻璃(BG)增强的生物复合膜,有望应用于组织工程(TE)。使用 25 kGy 伽马射线对 BG/PCL/CS 生物复合薄膜进行灭菌,并通过机械和物理评估、浸泡在模拟体液 (SBF) 中进行生物活性评估以及使用人类原生真皮成纤维细胞 (HPDF) 进行生物相容性检查,分析其随后的特性变化。结果表明,BG 颗粒在 BG/PCL/CS 聚合物基质中分布均匀,增强了生物活性,而且聚合物混合物提供了结构稳定的薄膜。由于光氧化降解,伽马射线照射导致薄膜表面粗糙度增加;但这并没有对玻璃微粒和聚合物链的完整性产生不利影响。体外评估显示,薄膜表面形成了羟基磷灰石,这表明薄膜具有生物活性。生物相容性测试证实,细胞粘附和增殖能力增强。这些多功能特性凸显了所制造的 BG/PCL/CS 生物复合薄膜在 TE 和再生医学应用方面的潜力。
{"title":"Effects of Gamma Irradiation on Structural, Chemical, Bioactivity and Biocompatibility Characteristics of Bioactive Glass–Polymer Composite Film","authors":"Mamun Khan Sujon,&nbsp;Siti Fatimah Samsurrijal,&nbsp;Ruzalina Baharin,&nbsp;Naurah Mat Isa,&nbsp;Muhammad Azrul Zabidi,&nbsp;Siti Noor Fazliah Mohd Noor","doi":"10.1002/jbm.a.37842","DOIUrl":"10.1002/jbm.a.37842","url":null,"abstract":"<div>\u0000 \u0000 <p>Gamma irradiation is an effective technique for biocomposite films intended for application in tissue engineering (TE) to ensure sterility and patient safety prior to clinical applications. This study proposed a biocomposite film composed of natural polymer chitosan (CS) and synthetic polymer poly-Ɛ-caprolactone (PCL) reinforced with sol–gel-derived bioactive glass (BG) for potential application in TE. The BG/PCL/CS biocomposite film was sterilized using 25 kGy gamma rays, and subsequent changes in its characteristics were analyzed through mechanical and physical assessment, bioactivity evaluation via immersion in simulated body fluid (SBF) and biocompatibility examination using human primary dermal fibroblasts (HPDFs). Results indicated a homogeneous distribution of BG particles within the BG/PCL/CS polymer matrix which enhanced bioactivity, and the polymer blend provide a structurally stable film. Gamma irradiation induced an increase in the film's surface roughness due to photo-oxidative degradation; however, this did not adversely affect the integrity of glass particles and polymer chains. In vitro assessments demonstrated hydroxyapatite formation on the film's surface, suggesting bioactivity. Biocompatibility testing confirmed enhanced cell adhesion and proliferation. These multifunctional properties highlight the potential of the fabricated BG/PCL/CS biocomposite film for TE and regenerative medicine applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tuning Surface Chemistry Impacts on Cardiac Endothelial and Smooth Muscle Cell Development 调节表面化学对心脏内皮细胞和平滑肌细胞发育的影响。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-13 DOI: 10.1002/jbm.a.37846
Yasemin Acar, Amy Managh, Eric James Hill, Paul Roach

Cardiovascular diseases (CVDs) are the leading causes of death worldwide, with approx. Twenty million deaths in 2021. Cardiovascular implants are among the most used biomaterials in the clinical world. However, poor endothelialisation and rapid thrombosis remains a challenge. Simple chemical surface modification techniques can be used to steer biological interactions without affecting the bioimplants' overall bulk characteristics such as radiopacity and flexibility. Although silanes are well studied for protein and cell interactions, the methodical investigation of cardiac endothelial cell (EC) alongside smooth muscle cell (SMC) to mimic natural arterial environments has been limited. In this study, these cells have been investigated on surfaces functionalized with methyl, amine, thiol, methacrylate, and fluorine organosilane groups. Cardiac EC and SMC growth was investigated with metabolic activity, time lapse imaging, and immunofluorescent staining techniques. The results demonstrated that the surfaces tested are able to selectively regulate the viability and growth of the cells. Aminosilane modified surfaces displayed 2-fold higher metabolic activity with HUVEC and 2-fold less metabolic activity with HCASMC cell lines, compared to tissue culture plastic controls. The amino-modification outperformed all other chemistries tested in terms of ability to promote the proliferation of ECs, while importantly reducing the activity of SMCs. This report demonstrates that aminosilane modified surfaces have the potential to be utilized in novel cardiovascular implants, which could improve biological integration in the short and possibly longer-term. The findings of this study suggest that specific chemical modifications of the surface can enhance endothelial cell activity while minimizing the proliferation of smooth muscle cells, which are often associated with thrombosis. This highlights the potential of carefully engineered surface chemistries to improve the clinical outcomes of cardiovascular implants.

心血管疾病(CVD)是导致全球死亡的主要原因,2021 年将有约 2000 万人死于此病。心血管植入物是临床上使用最多的生物材料之一。然而,内皮化不良和快速血栓形成仍然是一个挑战。简单的化学表面改性技术可用于引导生物相互作用,而不影响生物植入物的整体体积特性,如辐射性和柔韧性。虽然硅烷对蛋白质和细胞的相互作用研究得很透彻,但对心脏内皮细胞(EC)和平滑肌细胞(SMC)模拟自然动脉环境的方法研究还很有限。在这项研究中,研究人员在具有甲基、胺、硫醇、甲基丙烯酸酯和氟有机硅烷基团功能化的表面上对这些细胞进行了研究。通过新陈代谢活动、延时成像和免疫荧光染色技术对心脏 EC 和 SMC 的生长进行了研究。结果表明,所测试的表面能够选择性地调节细胞的活力和生长。与组织培养塑料对照组相比,氨基硅烷修饰表面对 HUVEC 的代谢活性高 2 倍,对 HCASMC 细胞株的代谢活性低 2 倍。就促进 EC 增殖的能力而言,氨基修饰的效果优于所有其他测试过的化学物质,但重要的是,它降低了 SMC 的活性。本报告表明,氨基硅烷改性表面有可能用于新型心血管植入物,从而在短期甚至长期内改善生物整合。这项研究的结果表明,对表面进行特定的化学修饰可以增强内皮细胞的活性,同时最大限度地减少平滑肌细胞的增殖,而平滑肌细胞的增殖往往与血栓形成有关。这凸显了精心设计的表面化学物质在改善心血管植入物临床效果方面的潜力。
{"title":"Tuning Surface Chemistry Impacts on Cardiac Endothelial and Smooth Muscle Cell Development","authors":"Yasemin Acar,&nbsp;Amy Managh,&nbsp;Eric James Hill,&nbsp;Paul Roach","doi":"10.1002/jbm.a.37846","DOIUrl":"10.1002/jbm.a.37846","url":null,"abstract":"<p>Cardiovascular diseases (CVDs) are the leading causes of death worldwide, with approx. Twenty million deaths in 2021. Cardiovascular implants are among the most used biomaterials in the clinical world. However, poor endothelialisation and rapid thrombosis remains a challenge. Simple chemical surface modification techniques can be used to steer biological interactions without affecting the bioimplants' overall bulk characteristics such as radiopacity and flexibility. Although silanes are well studied for protein and cell interactions, the methodical investigation of cardiac endothelial cell (EC) alongside smooth muscle cell (SMC) to mimic natural arterial environments has been limited. In this study, these cells have been investigated on surfaces functionalized with methyl, amine, thiol, methacrylate, and fluorine organosilane groups. Cardiac EC and SMC growth was investigated with metabolic activity, time lapse imaging, and immunofluorescent staining techniques. The results demonstrated that the surfaces tested are able to selectively regulate the viability and growth of the cells. Aminosilane modified surfaces displayed 2-fold higher metabolic activity with HUVEC and 2-fold less metabolic activity with HCASMC cell lines, compared to tissue culture plastic controls. The amino-modification outperformed all other chemistries tested in terms of ability to promote the proliferation of ECs, while importantly reducing the activity of SMCs. This report demonstrates that aminosilane modified surfaces have the potential to be utilized in novel cardiovascular implants, which could improve biological integration in the short and possibly longer-term. The findings of this study suggest that specific chemical modifications of the surface can enhance endothelial cell activity while minimizing the proliferation of smooth muscle cells, which are often associated with thrombosis. This highlights the potential of carefully engineered surface chemistries to improve the clinical outcomes of cardiovascular implants.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37846","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Decellularized Extracellular Matrix and Polyurethane Vascular Grafts Have Positive Effects on the Inflammatory and Pro-Thrombotic State of Aged Endothelial Cells 脱细胞细胞外基质和聚氨酯血管移植物对衰老内皮细胞的炎症和促血栓状态有积极影响。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-29 DOI: 10.1002/jbm.a.37830
Sophie J. Specht, Sabrina Rohringer, Pia Hager, Christian Grasl, Anna-Maria Schmitt, Virginia J. C. Pach, Katharina Ehrmann, Stefan Baudis, Robert Liska, Herbert Kiss, Karl H. Schneider, Bruno K. Podesser, Helga Bergmeister

In vitro assessment of small-diameter synthetic vascular grafts usually uses standard cell culture conditions with early-passage cells. However, these conduits are mainly implanted in elderly patients and are subject to complex cellular interactions influenced by age and inflammation. Understanding these factors is central to the development of vascular grafts tailored to the specific needs of patients. In this study, the effects of aged endothelial cells subjected to pro- and anti-inflammatory agents and cultivated on a newly developed biodegradable electrospun thermoplastic polyurethane/poly(urethane-urea) blend (TPU/TPUU), on clinically available expanded polytetrafluorethylene (ePTFE), and on decellularized extracellular matrix (dECM) grafts were investigated. Young and aged endothelial cells were exposed to pro- and anti-inflammatory agents and characterized by morphology, migration capacity, and gene expression. In addition, the cells were seeded onto the various graft materials and examined microscopically alongside gene expression analyses. When exposed to pro-inflammatory cytokines, young and aged cells demonstrated signs of endothelial activation. Cells seeded on ePTFE showed reduced attachment and increased expression of pro-inflammatory genes compared with the other materials. dECM and TPU/TPUU substrates provided better support for endothelialization with aged cells under inflammatory conditions compared with ePTFE. Moreover, TPU/TPUU showed positive effects on reducing pro-thrombotic and pro-inflammatory gene expression in endothelial cells. Our results thus emphasize the importance of developing new synthetic graft materials as an alternative for clinically used ePTFE.

体外评估小直径合成血管移植物通常采用早期传代细胞的标准细胞培养条件。然而,这些导管主要植入老年患者,并且受到年龄和炎症影响的复杂细胞相互作用的影响。了解这些因素对于开发适合患者特定需求的血管移植至关重要。在这项研究中,老化的内皮细胞受到抗炎剂和抗炎剂的影响,并在新开发的可生物降解的静电纺热塑性聚氨酯/聚(聚氨酯-尿素)共混物(TPU/TPUU)上培养,对临床可用的膨胀聚四氟乙烯(ePTFE)和脱细胞细胞外基质(dECM)移植物进行了研究。年轻和年老的内皮细胞暴露于促炎剂和抗炎剂中,并以形态学、迁移能力和基因表达为特征。此外,将细胞播种到各种移植材料上,并在显微镜下检查基因表达分析。当暴露于促炎细胞因子时,年轻和年老的细胞表现出内皮活化的迹象。与其他材料相比,ePTFE上的细胞附着减少,促炎基因表达增加。与ePTFE相比,dECM和TPU/TPUU底物对炎症条件下老化细胞的内皮化提供了更好的支持。此外,TPU/TPUU对降低内皮细胞促血栓和促炎症基因表达有积极作用。因此,我们的结果强调了开发新的合成移植物材料作为临床使用ePTFE的替代品的重要性。
{"title":"Decellularized Extracellular Matrix and Polyurethane Vascular Grafts Have Positive Effects on the Inflammatory and Pro-Thrombotic State of Aged Endothelial Cells","authors":"Sophie J. Specht,&nbsp;Sabrina Rohringer,&nbsp;Pia Hager,&nbsp;Christian Grasl,&nbsp;Anna-Maria Schmitt,&nbsp;Virginia J. C. Pach,&nbsp;Katharina Ehrmann,&nbsp;Stefan Baudis,&nbsp;Robert Liska,&nbsp;Herbert Kiss,&nbsp;Karl H. Schneider,&nbsp;Bruno K. Podesser,&nbsp;Helga Bergmeister","doi":"10.1002/jbm.a.37830","DOIUrl":"10.1002/jbm.a.37830","url":null,"abstract":"<p>In vitro assessment of small-diameter synthetic vascular grafts usually uses standard cell culture conditions with early-passage cells. However, these conduits are mainly implanted in elderly patients and are subject to complex cellular interactions influenced by age and inflammation. Understanding these factors is central to the development of vascular grafts tailored to the specific needs of patients. In this study, the effects of aged endothelial cells subjected to pro- and anti-inflammatory agents and cultivated on a newly developed biodegradable electrospun thermoplastic polyurethane/poly(urethane-urea) blend (TPU/TPUU), on clinically available expanded polytetrafluorethylene (ePTFE), and on decellularized extracellular matrix (dECM) grafts were investigated. Young and aged endothelial cells were exposed to pro- and anti-inflammatory agents and characterized by morphology, migration capacity, and gene expression. In addition, the cells were seeded onto the various graft materials and examined microscopically alongside gene expression analyses. When exposed to pro-inflammatory cytokines, young and aged cells demonstrated signs of endothelial activation. Cells seeded on ePTFE showed reduced attachment and increased expression of pro-inflammatory genes compared with the other materials. dECM and TPU/TPUU substrates provided better support for endothelialization with aged cells under inflammatory conditions compared with ePTFE. Moreover, TPU/TPUU showed positive effects on reducing pro-thrombotic and pro-inflammatory gene expression in endothelial cells. Our results thus emphasize the importance of developing new synthetic graft materials as an alternative for clinically used ePTFE.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
In Vitro Osteogenic Response to Copper-Doped Eggshell-Derived Hyroxyapatite With Macrophage Supplements 巨噬细胞补充铜掺杂蛋壳衍生羟基磷灰石的体外成骨反应
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-29 DOI: 10.1002/jbm.a.37838
Tejal V. Patil, Dinesh K. Patel, Ki-Taek Lim

The high bioactivity and biocompatibility of hydroxyapatite (HAP) make it a useful bone graft material for bone tissue engineering. However, the development superior osteoconductive and osteoinductive materials for bone regeneration remains a challenge. To overcome these constraints, Cu-doped hydroxyapatite (HAP(Cu)) from waste eggshells has been produced for bone tissue engineering. The materials produced were characterized using Fourier transform infrared spectroscopy, x-ray diffraction, and photoelectron spectroscopy. The scanning microscopy images revealed that the developed HAP was a rod-like crystalline structure with a typical 80–150 nm diameter. Energy-dispersive x-ray spectroscopy showed that the generated HAP was mostly composed of calcium, oxygen, and phosphorus. The Ca/P molar ratios in eggshell-derived and copper-doped HAP were 1.61 and 1.67, respectively, similar to the commercially available HAP ratio (1.67). The WST-8 assay was used to assess the biocompatibility of HAPs with hBMSCs. HAP(Cu) in the media significantly altered the cytotoxicity of biocompatible HAP(Cu). The osteogenic potential of HAP(Cu) was demonstrated by greater mineralization than that of pure HAP or the control. HAP(Cu) showed higher osteogenic gene expression than pure HAP and the control, indicating its stronger osteogenic potential. Furthermore, we assessed the effects of sample-treated macrophage-derived conditioned medium (CM) on hBMSCs' osteogenesis. CM-treated HAP(Cu) demonstrated a significantly higher osteogenic potential vis-à-vis pure HAP(Cu). These findings revealed that HAP(Cu) with CM significantly improved osteogenesis in hBMSCs and can be explored as a bone graft in bone tissue engineering.

羟基磷灰石(HAP)具有较高的生物活性和生物相容性,是骨组织工程中有用的骨移植材料。然而,开发优良的骨传导和骨诱导材料用于骨再生仍然是一个挑战。为了克服这些限制,从废蛋壳中制备出掺铜羟基磷灰石(HAP(Cu))用于骨组织工程。利用傅里叶变换红外光谱、x射线衍射和光电子能谱对所制备的材料进行了表征。扫描显微镜图像显示,发育的HAP为典型的80 ~ 150nm直径的棒状晶体结构。能量色散x射线光谱分析表明,生成的HAP主要由钙、氧和磷组成。蛋壳衍生HAP和铜掺杂HAP的Ca/P摩尔比分别为1.61和1.67,与市售HAP的摩尔比(1.67)相似。采用WST-8法评价hap与hBMSCs的生物相容性。培养基中的HAP(Cu)显著改变了生物相容性HAP(Cu)的细胞毒性。与纯HAP或对照相比,HAP(Cu)的矿化程度更高,表明HAP(Cu)具有成骨潜能。HAP(Cu)的成骨基因表达量高于纯HAP和对照,表明其具有更强的成骨潜能。此外,我们评估了样品处理的巨噬细胞衍生条件培养基(CM)对hBMSCs成骨的影响。与-à-vis纯HAP(Cu)相比,cm处理的HAP(Cu)表现出明显更高的成骨潜能。这些结果表明,含CM的HAP(Cu)可显著促进hBMSCs的成骨,可作为骨组织工程中的骨移植物进行探索。
{"title":"In Vitro Osteogenic Response to Copper-Doped Eggshell-Derived Hyroxyapatite With Macrophage Supplements","authors":"Tejal V. Patil,&nbsp;Dinesh K. Patel,&nbsp;Ki-Taek Lim","doi":"10.1002/jbm.a.37838","DOIUrl":"https://doi.org/10.1002/jbm.a.37838","url":null,"abstract":"<div>\u0000 \u0000 <p>The high bioactivity and biocompatibility of hydroxyapatite (HAP) make it a useful bone graft material for bone tissue engineering. However, the development superior osteoconductive and osteoinductive materials for bone regeneration remains a challenge. To overcome these constraints, Cu-doped hydroxyapatite (HAP(Cu)) from waste eggshells has been produced for bone tissue engineering. The materials produced were characterized using Fourier transform infrared spectroscopy, x-ray diffraction, and photoelectron spectroscopy. The scanning microscopy images revealed that the developed HAP was a rod-like crystalline structure with a typical 80–150 nm diameter. Energy-dispersive x-ray spectroscopy showed that the generated HAP was mostly composed of calcium, oxygen, and phosphorus. The Ca/P molar ratios in eggshell-derived and copper-doped HAP were 1.61 and 1.67, respectively, similar to the commercially available HAP ratio (1.67). The WST-8 assay was used to assess the biocompatibility of HAPs with hBMSCs. HAP(Cu) in the media significantly altered the cytotoxicity of biocompatible HAP(Cu). The osteogenic potential of HAP(Cu) was demonstrated by greater mineralization than that of pure HAP or the control. HAP(Cu) showed higher osteogenic gene expression than pure HAP and the control, indicating its stronger osteogenic potential. Furthermore, we assessed the effects of sample-treated macrophage-derived conditioned medium (CM) on hBMSCs' osteogenesis. CM-treated HAP(Cu) demonstrated a significantly higher osteogenic potential vis-à-vis pure HAP(Cu). These findings revealed that HAP(Cu) with CM significantly improved osteogenesis in hBMSCs and can be explored as a bone graft in bone tissue engineering.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Albumin/Hyaluronic Acid Nanoparticle-Laden Contact Lenses for the Ocular Delivery of 5-Fluorouracil 携带白蛋白/透明质酸纳米颗粒的隐形眼镜用于眼部给药5-氟尿嘧啶
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-29 DOI: 10.1002/jbm.a.37839
Sara F. M. Senra, Sérgio R. S. Veloso, Madalena Lira, Elisabete M. S. Castanheira

Nanoparticle-laden contact lenses are a formidable strategy for ocular drug delivery. However, incorporating nanoparticles to achieve sustained drug release without affecting the contact lenses' properties remains a challenging task. In this work, daily and monthly replacement silicone-hydrogel contact lenses laden with bovine serum albumin/hyaluronic acid (BSA/HA) nanoparticles are presented. These nanoparticle-laden contact lenses enable the sustained release of 5-fluorouracil (5-FU) in mimetic physiological conditions. The nanoparticle-laden contact lenses display properties similar to neat contact lenses, including refractive index, water content, UV/visible transmittance and chemical structure. Noteworthy attributes include the BSA/HA nanoparticles' low polydispersity, negative surface charge and a hydrodynamic size of ~210 nm, as well as the high nanoparticle loading efficiency (~ 30%) of the contact lenses. Thereby, the BSA/HA nanoparticles are a promising strategy for developing nanoparticle-laden contact lenses for therapeutic applications, namely for sustained drug delivery.

携带纳米粒子的隐形眼镜是一种强大的眼部药物输送策略。然而,结合纳米颗粒在不影响隐形眼镜性能的情况下实现持续的药物释放仍然是一项具有挑战性的任务。在这项工作中,介绍了每天和每月更换含有牛血清白蛋白/透明质酸(BSA/HA)纳米颗粒的硅水凝胶隐形眼镜。这些纳米颗粒负载的隐形眼镜能够在模拟生理条件下持续释放5-氟尿嘧啶(5-FU)。纳米颗粒隐形眼镜显示出与普通隐形眼镜相似的性能,包括折射率、含水量、紫外线/可见光透过率和化学结构。值得注意的是,BSA/HA纳米颗粒的多分散性低,表面带负电荷,水动力尺寸为~210 nm,并且隐形眼镜的纳米颗粒负载效率高(~ 30%)。因此,BSA/HA纳米颗粒是一种很有前途的策略,用于开发用于治疗应用的纳米颗粒负载隐形眼镜,即持续给药。
{"title":"Albumin/Hyaluronic Acid Nanoparticle-Laden Contact Lenses for the Ocular Delivery of 5-Fluorouracil","authors":"Sara F. M. Senra,&nbsp;Sérgio R. S. Veloso,&nbsp;Madalena Lira,&nbsp;Elisabete M. S. Castanheira","doi":"10.1002/jbm.a.37839","DOIUrl":"https://doi.org/10.1002/jbm.a.37839","url":null,"abstract":"<div>\u0000 \u0000 <p>Nanoparticle-laden contact lenses are a formidable strategy for ocular drug delivery. However, incorporating nanoparticles to achieve sustained drug release without affecting the contact lenses' properties remains a challenging task. In this work, daily and monthly replacement silicone-hydrogel contact lenses laden with bovine serum albumin/hyaluronic acid (BSA/HA) nanoparticles are presented. These nanoparticle-laden contact lenses enable the sustained release of 5-fluorouracil (5-FU) in mimetic physiological conditions. The nanoparticle-laden contact lenses display properties similar to neat contact lenses, including refractive index, water content, UV/visible transmittance and chemical structure. Noteworthy attributes include the BSA/HA nanoparticles' low polydispersity, negative surface charge and a hydrodynamic size of ~210 nm, as well as the high nanoparticle loading efficiency (~ 30%) of the contact lenses. Thereby, the BSA/HA nanoparticles are a promising strategy for developing nanoparticle-laden contact lenses for therapeutic applications, namely for sustained drug delivery.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Graphene Oxide Functionalized GelMA Platform Loaded With BFP-1 for Osteogenic Differentiation of BMSCs 负载BFP-1的氧化石墨烯功能化GelMA平台用于骨髓间充质干细胞成骨分化
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-29 DOI: 10.1002/jbm.a.37829
Taowen Guo, Shifan Lin, Le Zou, Guoliang Zhang, Jiaqi Long, Zhiping Zhang, Shan Wang

Spinal fusion is the ultimate choice for most patients with severe disc degeneration, and bone tissue engineering offers novel strategies to improve intervertebral bone growth and fusion. In this study, we utilized graphene oxide (GO) and methacrylated gelatin (GelMA) to prepare GelMA/GO composite hydrogel scaffolds with different GO concentrations. By characterizing the various properties of the scaffolds, it was learned that the composite scaffold containing 1.2 mg/mL GO possessed the best overall performance, and we used it for subsequent experiments. GelMA/GO composite scaffolds containing different bone-forming peptide-1 (BFP-1) concentrations were constructed and cocultured with bone marrow mesenchymal stem cells (BMSCs), and the results showed that GelMA/GO composite scaffolds containing 0.4 mg/mL BFP-1 induced the cells to produce more ALP and mineralized matrix. The above scaffold was further investigated as a GelMA/GO@BFP-1 composite, and the results showed that it promoted the production of ALP and mineralized matrix in BMSCs, and significantly enhanced the expression of osteogenesis-related genes (ALP, Runx-2, OCN, OPN) and proteins (Runx-2, OCN). It suggests that the GelMA/GO@BFP-1 complex promotes osteogenic differentiation of BMSCs and has the potential tobe used as a bone implant for improving intervertebral bone fusion.

脊柱融合是大多数严重椎间盘退变患者的最终选择,骨组织工程为改善椎间骨生长和融合提供了新的策略。在本研究中,我们利用氧化石墨烯(GO)和甲基丙烯酸明胶(GelMA)制备了不同氧化石墨烯浓度的GelMA/GO复合水凝胶支架。通过对支架各项性能的表征,得知含1.2 mg/mL氧化石墨烯的复合支架综合性能最好,我们将其用于后续实验。构建不同骨形成肽-1 (BFP-1)浓度的GelMA/GO复合支架,并与骨髓间充质干细胞共培养,结果表明,含有0.4 mg/mL BFP-1的GelMA/GO复合支架可诱导细胞产生更多的ALP和矿化基质。进一步将上述支架作为GelMA/GO@BFP-1复合材料进行研究,结果表明其促进了BMSCs中ALP和矿化基质的生成,并显著增强了成骨相关基因(ALP、Runx-2、OCN、OPN)和蛋白(Runx-2、OCN)的表达。这表明GelMA/GO@BFP-1复合物促进骨髓间充质干细胞的成骨分化,并有潜力用作骨植入物以改善椎间骨融合。
{"title":"Graphene Oxide Functionalized GelMA Platform Loaded With BFP-1 for Osteogenic Differentiation of BMSCs","authors":"Taowen Guo,&nbsp;Shifan Lin,&nbsp;Le Zou,&nbsp;Guoliang Zhang,&nbsp;Jiaqi Long,&nbsp;Zhiping Zhang,&nbsp;Shan Wang","doi":"10.1002/jbm.a.37829","DOIUrl":"https://doi.org/10.1002/jbm.a.37829","url":null,"abstract":"<p>Spinal fusion is the ultimate choice for most patients with severe disc degeneration, and bone tissue engineering offers novel strategies to improve intervertebral bone growth and fusion. In this study, we utilized graphene oxide (GO) and methacrylated gelatin (GelMA) to prepare GelMA/GO composite hydrogel scaffolds with different GO concentrations. By characterizing the various properties of the scaffolds, it was learned that the composite scaffold containing 1.2 mg/mL GO possessed the best overall performance, and we used it for subsequent experiments. GelMA/GO composite scaffolds containing different bone-forming peptide-1 (BFP-1) concentrations were constructed and cocultured with bone marrow mesenchymal stem cells (BMSCs), and the results showed that GelMA/GO composite scaffolds containing 0.4 mg/mL BFP-1 induced the cells to produce more ALP and mineralized matrix. The above scaffold was further investigated as a GelMA/GO@BFP-1 composite, and the results showed that it promoted the production of ALP and mineralized matrix in BMSCs, and significantly enhanced the expression of osteogenesis-related genes (ALP, Runx-2, OCN, OPN) and proteins (Runx-2, OCN). It suggests that the GelMA/GO@BFP-1 complex promotes osteogenic differentiation of BMSCs and has the potential tobe used as a bone implant for improving intervertebral bone fusion.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37829","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design of PEG-Based Hydrogels as Soft Ionic Conductors 设计作为软离子导体的 PEG 基水凝胶。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-23 DOI: 10.1002/jbm.a.37840
Gabriel J. Rodriguez-Rivera, Fei Xu, Madeline Laude, Vani Shah, Abbey Nkansah, Derek Bashe, Ziyang Lan, Malgorzata Chwatko, Elizabeth Cosgriff-Hernandez

Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical properties in previous studies, our investigation aimed to understand the pivotal structural factors that impact the conductivity and mechanical behavior of polyethylene glycol (PEG)-based hydrogels with ionic conductivity. Polyether urethane diacrylamide (PEUDAm), a functionalized long-chain macromer based on PEG, was used to synthesize hydrogels with ionic conductivity conferred by incorporating ions into the liquid phase of the hydrogel. The impact of salt concentration, water content, temperature, and gel formation on both mechanical properties and conductivity was characterized to establish parameters for tuning hydrogel properties. To further expand the range of conductivity available in these ionic hydrogels, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was incorporated as a single copolymer network or double network configuration. As expected, conductivity in these ionic gels was primarily driven by ion diffusivity and charge density, which were dependent on hydrogel network formation and swelling. Copolymer network structure had minimal effect on the conductivity, which was primarily driven by counter-ion equilibrium; however, the mechanical properties and equilibrium swelling were strongly dependent on network structure. The structure–property relationships elucidated here enable the rationale design of this new double network hydrogel to achieve target properties for a broad range of biomedical applications.

导电水凝胶在生物医学应用和软电子学领域备受关注。为了解决以往研究中离子水凝胶无法达到理想机械性能的难题,我们的研究旨在了解影响具有离子导电性的聚乙二醇(PEG)基水凝胶的导电性和机械行为的关键结构因素。聚醚聚氨酯二丙烯酰胺(PEUDAm)是一种基于 PEG 的官能化长链大单体,我们用它来合成具有离子导电性的水凝胶,方法是在水凝胶的液相中加入离子。研究表征了盐浓度、水含量、温度和凝胶形成对机械性能和电导率的影响,从而确定了调整水凝胶性能的参数。为了进一步扩大这些离子水凝胶的电导率范围,2-丙烯酰胺基-2-甲基-1-丙磺酸(AMPS)以单共聚物网络或双网络配置的形式加入其中。不出所料,这些离子凝胶的导电性主要受离子扩散率和电荷密度的影响,而离子扩散率和电荷密度取决于水凝胶网络的形成和溶胀。共聚物网络结构对电导率的影响很小,电导率主要由反离子平衡驱动;然而,机械性能和平衡溶胀在很大程度上取决于网络结构。本文所阐明的结构-性能关系有助于合理设计这种新型双网络水凝胶,使其在广泛的生物医学应用中实现目标性能。
{"title":"Design of PEG-Based Hydrogels as Soft Ionic Conductors","authors":"Gabriel J. Rodriguez-Rivera,&nbsp;Fei Xu,&nbsp;Madeline Laude,&nbsp;Vani Shah,&nbsp;Abbey Nkansah,&nbsp;Derek Bashe,&nbsp;Ziyang Lan,&nbsp;Malgorzata Chwatko,&nbsp;Elizabeth Cosgriff-Hernandez","doi":"10.1002/jbm.a.37840","DOIUrl":"10.1002/jbm.a.37840","url":null,"abstract":"<div>\u0000 \u0000 <p>Conductive hydrogels have gained interest in biomedical applications and soft electronics. To tackle the challenge of ionic hydrogels falling short of desired mechanical properties in previous studies, our investigation aimed to understand the pivotal structural factors that impact the conductivity and mechanical behavior of polyethylene glycol (PEG)-based hydrogels with ionic conductivity. Polyether urethane diacrylamide (PEUDAm), a functionalized long-chain macromer based on PEG, was used to synthesize hydrogels with ionic conductivity conferred by incorporating ions into the liquid phase of the hydrogel. The impact of salt concentration, water content, temperature, and gel formation on both mechanical properties and conductivity was characterized to establish parameters for tuning hydrogel properties. To further expand the range of conductivity available in these ionic hydrogels, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) was incorporated as a single copolymer network or double network configuration. As expected, conductivity in these ionic gels was primarily driven by ion diffusivity and charge density, which were dependent on hydrogel network formation and swelling. Copolymer network structure had minimal effect on the conductivity, which was primarily driven by counter-ion equilibrium; however, the mechanical properties and equilibrium swelling were strongly dependent on network structure. The structure–property relationships elucidated here enable the rationale design of this new double network hydrogel to achieve target properties for a broad range of biomedical applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance 将聚乳酸(PLLA)多孔支架作为研究抗药性的三维乳腺癌模型
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-16 DOI: 10.1002/jbm.a.37836
Camilla Carbone, Salvatrice Rigogliuso, Valerio Maria Bartolo Brucato, Alessandra Cusimano, Manuela Labbozzetta, Vincenzo La Carrubba, Paola Poma, Monica Notarbartolo, Francesco Carfì Pavia

Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-l-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC50 values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC50 was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC50, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.

多药耐药性仍是乳腺癌研究的主要挑战之一,往往导致治疗失败。为了更好地了解这一机制,有必要建立复杂的三维(3D)肿瘤模型,因为与传统的二维(2D)培养相比,三维(3D)肿瘤模型具有多种优势。本研究采用热诱导相分离技术制备了聚乳酸多孔支架,并将其用作乳腺癌细胞系的三维模型:MDA-MB-231、MCF-7 及其耐多药变体 MCF-7R。MTS 检测法用于比较二维和三维多柔比星处理后的生长抑制情况。值得注意的是,与二维培养相比,三维培养的 IC50 值有所增加:MDA-MB-231(445 vs. 54.5 ng/mL)、MCF-7(7.45 vs. 0.75 μg/mL)和 MCF-7R(165 vs. 39 μg/mL)。MCF-7R通常在2D中表现出更强的抗药性,但在3D中表现出更强的抗药性。事实上,它并不像其他模型那样在 3 天内达到 IC50,而是在 6 天后才达到。细胞形态也起着至关重要的作用。当处理浓度高于 IC50 时,MDA-MB-231 细胞失去了生理性的三维团状结构,而 MCF-7 及其抗性变体则表现出层状破坏。三维结构中的所有细胞株都表现出更高的化疗耐受性,这表明它们的空间结构更具生物仿生性。我们的研究填补了单层模型和动物模型之间的空白,凸显了聚合物三维支架在乳腺癌研究中的潜力。
{"title":"PLLA Porous Scaffold as a 3D Breast Cancer Model to Investigate Drug Resistance","authors":"Camilla Carbone,&nbsp;Salvatrice Rigogliuso,&nbsp;Valerio Maria Bartolo Brucato,&nbsp;Alessandra Cusimano,&nbsp;Manuela Labbozzetta,&nbsp;Vincenzo La Carrubba,&nbsp;Paola Poma,&nbsp;Monica Notarbartolo,&nbsp;Francesco Carfì Pavia","doi":"10.1002/jbm.a.37836","DOIUrl":"10.1002/jbm.a.37836","url":null,"abstract":"<div>\u0000 \u0000 <p>Multidrug resistance remains one of the major challenges in breast cancer research, often leading to treatment failure. To better understand this mechanism, sophisticated three-dimensional (3D) tumor models are necessary, as they offer several advantages over traditional bidimensional (2D) cultures. In this study, poly-<span>l</span>-lactic-acid porous scaffolds were produced using a thermally induced phase separation technique and employed as 3D models for breast cancer cell lines: MDA-MB-231, MCF-7, and its multidrug-resistant variant, MCF-7R. The MTS assay was used to compare growth inhibition following doxorubicin treatment in 2D and 3D. Remarkably, the IC<sub>50</sub> values increased in 3D cultures compared to 2D: MDA-MB-231 (445 vs. 54.5 ng/mL), MCF-7 (7.45 vs. 0.75 μg/mL), and MCF-7R (165 vs. 39 μg/mL). MCF-7R, which usually shows greater resistance in 2D, demonstrated even higher resistance in 3D. In fact, IC<sub>50</sub> was not reached within 3 days as with the other models, but only after 6 days. Cellular morphology also played a crucial role. When treated with concentrations higher than the IC<sub>50</sub>, MDA-MB-231 cells lost their physiological 3D clustered structure, while MCF-7 and its resistant variant exhibited disrupted layers. All cell lines in 3D showed higher chemoresistance, suggesting a more biomimetic spatial architecture. Our work bridges the gap between monolayer and animal models, highlighting the potential of polymeric 3D scaffolds in breast cancer research.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Topography-Mediated Induction of Epithelial Mesenchymal Transition via Alumina Textiles for Potential Wound Healing Applications 通过氧化铝纺织品诱导上皮间充质转化的拓扑结构,实现潜在的伤口愈合应用。
IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-11 DOI: 10.1002/jbm.a.37826
Deepanjalee Dutta, Titinun Nuntapramote, Maren Rehders, Klaudia Brix, Dorothea Brüggemann

Substrate topography is vital in determining cell growth and fate of cellular behavior. Although current in vitro studies of the underlying cellular signaling pathways mostly rely on their induction by specific growth factors or chemicals, the influence of substrate topography on specific changes in cells has been explored less often. This study explores the impact of substrate topography, specifically the tricot knit microfibrous structure of alumina textiles, on cell behavior, focusing on fibroblasts and keratinocytes for potential wound healing applications. The textiles, studied for the first time as in vitro substrates, demonstrated support for keratinocyte adhesion, leading to alterations in cell morphology and the expression of E-cadherin and fibronectin. These topography-induced changes resembled the epithelial-to-mesenchymal transition (EMT), crucial for wound healing, and were specific to keratinocytes and absent in identically treated fibroblasts. Biochemically induced EMT in keratinocytes cultured on flat alumina substrates mirrored the changes seen with alumina textiles alone, suggesting the tricot knit microfibrous topography could serve as an in vitro model system to induce EMT-like mechanisms. These results enhance our understanding of how substrate topography influences EMT-related processes in wound healing, paving the way for further evaluation of microfibrous alumina textiles as innovative wound dressings.

基底地形在决定细胞生长和细胞行为命运方面至关重要。尽管目前对潜在细胞信号通路的体外研究大多依赖于特定生长因子或化学物质的诱导,但较少探讨基底形貌对细胞特定变化的影响。本研究探讨了基底拓扑结构(特别是氧化铝纺织品的经编微纤维结构)对细胞行为的影响,重点研究了成纤维细胞和角质细胞在伤口愈合方面的潜在应用。首次将纺织品作为体外基质进行研究,结果表明,纺织品支持角质形成细胞的粘附,从而导致细胞形态以及 E 黏附因子和纤连蛋白的表达发生变化。这些地形诱导的变化类似于上皮细胞向间质转化(EMT),对伤口愈合至关重要,而且对角质形成细胞具有特异性,同样处理的成纤维细胞则没有这种变化。在平整的氧化铝基底上培养的角质形成细胞中,生化诱导的 EMT 与单独使用氧化铝纺织品时看到的变化相同,这表明经编微纤维拓扑可作为体外模型系统来诱导类似 EMT 的机制。这些结果加深了我们对基底拓扑如何影响伤口愈合中 EMT 相关过程的理解,为进一步评估氧化铝微纤维纺织品作为创新型伤口敷料铺平了道路。
{"title":"Topography-Mediated Induction of Epithelial Mesenchymal Transition via Alumina Textiles for Potential Wound Healing Applications","authors":"Deepanjalee Dutta,&nbsp;Titinun Nuntapramote,&nbsp;Maren Rehders,&nbsp;Klaudia Brix,&nbsp;Dorothea Brüggemann","doi":"10.1002/jbm.a.37826","DOIUrl":"10.1002/jbm.a.37826","url":null,"abstract":"<p>Substrate topography is vital in determining cell growth and fate of cellular behavior. Although current in vitro studies of the underlying cellular signaling pathways mostly rely on their induction by specific growth factors or chemicals, the influence of substrate topography on specific changes in cells has been explored less often. This study explores the impact of substrate topography, specifically the tricot knit microfibrous structure of alumina textiles, on cell behavior, focusing on fibroblasts and keratinocytes for potential wound healing applications. The textiles, studied for the first time as in vitro substrates, demonstrated support for keratinocyte adhesion, leading to alterations in cell morphology and the expression of E-cadherin and fibronectin. These topography-induced changes resembled the epithelial-to-mesenchymal transition (EMT), crucial for wound healing, and were specific to keratinocytes and absent in identically treated fibroblasts. Biochemically induced EMT in keratinocytes cultured on flat alumina substrates mirrored the changes seen with alumina textiles alone, suggesting the tricot knit microfibrous topography could serve as an in vitro model system to induce EMT-like mechanisms. These results enhance our understanding of how substrate topography influences EMT-related processes in wound healing, paving the way for further evaluation of microfibrous alumina textiles as innovative wound dressings.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Journal of biomedical materials research. Part A
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1