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Biphasic calcium phosphate doped with zirconia nanoparticles for reconstruction of induced mandibular defects in dogs: cone-beam computed tomographic and histopathologic evaluation 双相磷酸钙掺杂氧化锆纳米颗粒用于犬下颌缺损的重建:锥形束计算机断层扫描和组织病理学评估
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-19 DOI: 10.1007/s10856-023-06731-5
Said K. Taha, Elham A. Hassan, Sahar Mousa, Gehan T. El-Bassyouni, Heba N. Shalash, Mohamed A. Abdel Hamid

The present study aimed to evaluate osteogenic potential and biocompatibility of combining biphasic calcium phosphate with zirconia nanoparticles (4Zr TCP/HA) compared to biphasic calcium phosphate (TCP/HA) for reconstruction of induced mandibular defects in dog model. TCP/HA and 4Zr TCP/HA scaffolds were prepared. Morphological, physicochemical, antibacterial, cytocompatibility characterization were tested. In vivo application was performed in 12 dogs where three critical-sized mandibular defects were created in each dog. Bone defects were randomly allocated into: control, TCP/HA, and 4Zr TCP/HA groups. Bone density and bone area percentage were evaluated at 12 weeks using cone-beam computed tomographic, histopathologic, histomorphometric examination. Bone area density was statistically increased (p < 0.001) in TCP/HA and 4Zr TCP/HA groups compared to control group both in sagittal and coronal views. Comparing TCP/HA and 4Zr TCP/HA groups, the increase in bone area density was statistically significant in coronal view (p = 0.002) and sagittal view (p = 0.05). Histopathologic sections of TCP/HA group demonstrated incomplete filling of the defect with osteoid tissue. Doping with zirconia (4Zr TCP/HA group), resulted in statistically significant increase (p < 0.001) in bone formation (as indicated by bone area percentage) and maturation (as confirmed by Masson trichrome staining) compared to TCP/HA group. The newly formed bone was mature and organized with more trabecular thickness and less trabecular space in between. Physicochemical, morphological and bactericidal properties of combining zirconia and TCP/HA were improved. Combining zirconia and TCP/HA resulted in synergistic action with effective osteoinduction, osteoconduction and osteointegration suggesting its suitability to restore damaged bone in clinical practice.

Graphical Abstract

本研究旨在评价两相磷酸钙与氧化锆纳米颗粒(4Zr TCP/HA)联合修复犬下颌骨缺损的成骨潜力和生物相容性,并与两相磷酸钙(TCP/HA)进行比较。制备TCP/HA和4Zr TCP/HA支架。对其进行了形态、理化、抗菌、细胞相容性等方面的表征。在体内应用进行了12只狗,其中三个临界大小的下颌骨缺损在每只狗。骨缺损随机分为:对照组、TCP/HA组和4Zr TCP/HA组。12周时采用锥形束计算机断层扫描、组织病理学、组织形态学检查评估骨密度和骨面积百分比。在矢状面和冠状面上,TCP/HA和4Zr TCP/HA组的骨面积密度与对照组相比均有统计学增加(p < 0.001)。与TCP/HA和4Zr TCP/HA组比较,冠状面骨面积密度增加(p = 0.002),矢状面骨面积密度增加(p = 0.05)均有统计学意义。TCP/HA组组织病理切片显示骨样组织不完全填充缺损。与TCP/HA组相比,掺杂氧化锆(4Zr TCP/HA组)导致骨形成(骨面积百分比)和成熟(马松三色染色证实)有统计学意义(p < 0.001)的增加。新形成的骨成熟且有组织,骨小梁厚度增加,骨小梁之间的空间减少。氧化锆与TCP/HA复合材料的理化、形态和杀菌性能均得到改善。氧化锆与TCP/HA结合可产生协同作用,具有有效的骨诱导、骨传导和骨整合作用,适用于临床修复损伤骨。图形抽象
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引用次数: 1
Author Correction: Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats 作者更正:大鼠脊髓损伤模型中含氧化铈纳米纤维神经细胞再生的研究
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-16 DOI: 10.1007/s10856-023-06722-6
Behnaz Rahimi, Zahra Behroozi, Ali Motamednezhad, Maral Jafarpour, Michael R. Hamblin, Ali Moshiri, Atousa Janzadeh, Fatemeh Ramezani
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引用次数: 0
Electropolishing influence on biocompatibility of additively manufactured Ti-Nb-Ta-Zr: in vivo and in vitro 电抛光对增材制备Ti-Nb-Ta-Zr生物相容性的影响
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-14 DOI: 10.1007/s10856-023-06728-0
J. P. Luo, K. P. Lv, J. C. Tang, Z. Z. Wu, Y. L. Liu, J. T. Luo, Y. X. Lai, M. Yan

Balling defect of the additively manufactured titanium lattice implants easily leads to muscle tissue rejection, which might cause failure of implantation. Electropolishing is widely used in surface polishing of complex components and has potential to deal with the balling defect. However, a clad layer could be formed on the surface of titanium alloy after electropolishing, which may affect the biocompatibility of the metal implants. To manufacture lattice structured β-type Ti-Ni-Ta-Zr (TNTZ) for bio-medical applications, it is necessary to investigate the impact of electropolishing on material biocompatibility. In this study, animal experiments were conducted to investigate the in vivo biocompatibility of the as-printed TNTZ alloy with or without electropolishing; and proteomics technology was used to elaborate the results. The following conclusions were drawn: (a) a 30% oxalic acid electropolishing treatment was effective in solving balling defects, and ~21 nm amorphous clad layer would be formed on the surface of the material after polishing; (b) the electropolished TNTZ suggested decreased cell cytotoxicity and improved blood biocompatibility as compared to as-printed TNTZ; (c) the amorphous clad layer could make a barrier to prevent Ta and Zr ions from penetrating into the muscle tissue, and could form a good tissue regeneration at the implantation site during 4 weeks, indicating that the electropolished TNTZ has the potential as implants; and (d) the cells attached to the electropolished TNTZ showed higher antioxidant capacity but less proliferation than attached to as-printed TNTZ.

Graphical Abstract

增材制造的钛晶格植入物存在成球缺陷,容易引起肌肉组织排斥反应,导致植入失败。电抛光广泛应用于复杂零件的表面抛光,具有处理起球缺陷的潜力。然而,电解抛光后钛合金表面会形成包覆层,影响金属植入物的生物相容性。为了制造用于生物医学用途的晶格结构β型Ti-Ni-Ta-Zr (TNTZ),有必要研究电抛光对材料生物相容性的影响。本研究通过动物实验研究了经电抛光或不经电抛光后打印的TNTZ合金的体内生物相容性;并使用蛋白质组学技术来详细说明结果。得出以下结论:(a) 30%草酸电抛光处理能有效地解决起球缺陷,抛光后材料表面可形成~21 nm的非晶包层;(b)与打印的TNTZ相比,电抛光的TNTZ显示细胞毒性降低,血液生物相容性改善;(c)无定形包层能形成阻挡Ta和Zr离子渗入肌肉组织的屏障,并且在4周内能在植入部位形成良好的组织再生,表明电抛光TNTZ具有植入物的潜力;(d)电抛光TNTZ表面的细胞抗氧化能力比印刷TNTZ表面的细胞强,但增殖能力较差。图形抽象
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引用次数: 0
Effect of Chandler loop shear and tubing size on thrombus architecture 钱德勒环剪切和导管尺寸对血栓结构的影响
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-12 DOI: 10.1007/s10856-023-06721-7
Ziqian Zeng, Tanmaye Nallan Chakravarthula, Alexei Christodoulides, Abigail Hall, Nathan J. Alves

Thrombosis can lead to a wide variety of life-threatening circumstances. As current thrombolytic drug screening models often poorly predict drug profiles, leading to failure of thrombolytic therapy or clinical translation, more representative clot substrates are necessary for drug evaluation. Utilizing a Chandler loop device to form clot analogs at high shear has gained popularity in stroke societies. However, shear-dependent clot microstructure has not been fully addressed and low shear conditions are often overlooked. We herein characterized the impact of wall shear rate (126 to 951 s−1) on clot properties in the Chandler loop. Different revolutions (20–60) per minute and tubing sizes (3.2 to 7.9 mm) were employed to create different sized clots to mimic various thrombosis applications. Increased shear resulted in decreased RBC counts (76.9 ± 4.3% to 17.6 ± 0.9%) and increased fibrin (10 to 60%) based on clot histology. Increased fibrin sheet morphology and platelet aggregates were observed at higher shear under scanning electron microscope. These results show the significant impact of shear and tubing size on resulting clot properties and demonstrate the capability of forming a variety of reproducible in-vivo-like clot analogs in the Chandler loop device controlling for simple parameters to tune clot characteristics.

Graphical Abstract

血栓形成可导致多种危及生命的情况。由于目前的溶栓药物筛选模型往往不能很好地预测药物特征,导致溶栓治疗或临床转化的失败,因此需要更多具有代表性的凝块底物来进行药物评估。利用钱德勒环装置在高剪切下形成凝块类似物已在中风社会中得到普及。然而,剪切依赖的凝块微观结构尚未得到充分解决,低剪切条件往往被忽视。我们在此描述了壁剪切速率(126至951 s−1)对钱德勒环中凝块性质的影响。采用不同的转数(20-60)/分钟和不同的油管尺寸(3.2 - 7.9毫米)来创建不同大小的血栓,以模拟各种血栓形成应用。根据血块组织学,剪切增加导致红细胞计数减少(76.9±4.3%至17.6±0.9%),纤维蛋白增加(10%至60%)。在扫描电镜下观察到高剪切下纤维蛋白片形态和血小板聚集增加。这些结果表明,剪切和油管尺寸对产生的凝块特性有显著影响,并证明了在钱德勒环装置中形成各种可重复的体内样凝块类似物的能力,通过控制简单的参数来调整凝块特性。图形抽象
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引用次数: 1
Degree of conversion and residual monomer elution of 3D-printed, milled and self-cured resin-based composite materials for temporary dental crowns and bridges 用于临时牙冠和牙桥的3d打印、研磨和自固化树脂基复合材料的转化程度和剩余单体洗脱
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-05-12 DOI: 10.1007/s10856-023-06729-z
Eva Berghaus, Thorsten Klocke, Reinhard Maletz, Svea Petersen

The aim of this work was to investigate the elution of residual monomers as a function of the manufacturing process, which are CAD/CAM manufacturing, self-curing and 3D printing. The experimental materials used consisted of the base monomers TEGDMA, Bis-GMA and Bis-EMA and 50 wt.% fillers. Additionally, a 3D printing resin without fillers was tested. The elution of the base monomers into the different media (water, ethanol and ethanol/water (75/25 vol. %)) at 37 °C over a period of up to 120 d as well as the degree of conversion (DC) by FTIR were investigated. No monomer elution could be detected in water. Most residual monomers in both other media were released from the self-curing material whereas the 3D printing composite released relatively little. The CAD/CAM blanks released hardly any quantitatively detectable amounts of monomers. Relative to the base composition, TEGDMA eluted less than Bis-GMA and Bis-EMA. DC did not correlate with residual monomer release; thus, leaching was determined not only by the amount of residual monomers present but by further factors as possibly network density and structure. The CAD/CAM blanks and the 3D printing composite showed similar high DC but lower residual monomer release from the CAD/CAM blank, likewise the self-curing composite and the 3D printing resin exhibited similar DC but different monomer elution. In terms of residual monomer elution and DC, the 3D printing composite seems promising as a new material class for the use as temporary dental crowns and bridges.

Graphical Abstract

这项工作的目的是研究残余单体的洗脱作为制造过程的功能,这是CAD/CAM制造,自固化和3D打印。实验材料由基础单体TEGDMA、Bis-GMA和Bis-EMA和50%的填料组成。此外,还测试了一种不含填料的3D打印树脂。研究了碱单体在不同介质(水、乙醇和乙醇/水(75/25 vol. %))中在37°C下长达120 d的洗脱以及FTIR的转化率(DC)。水中未检出单体洗脱。其他两种介质中的大部分残留单体都是从自固化材料中释放出来的,而3D打印复合材料释放的相对较少。CAD/CAM毛坯几乎没有释放任何可定量检测的单体。相对于碱组成,TEGDMA洗脱量低于Bis-GMA和Bis-EMA。DC与单体残留释放量无相关性;因此,浸出不仅取决于存在的残余单体的数量,还取决于可能的网络密度和结构等其他因素。CAD/CAM毛坯和3D打印复合材料的DC相似,但单体残留量较低;自固化复合材料和3D打印树脂的DC相似,但单体洗脱量不同。在残余单体洗脱和DC方面,3D打印复合材料似乎很有希望作为一种新型材料用于临时牙冠和桥。图形抽象
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引用次数: 1
Bacterial response to Ti-35Nb-7Zr-5Ta alloy incorporated with calcium, phosphate and magnesium 细菌对加入钙、磷酸盐和镁的Ti-35Nb-7Zr-5Ta合金的反应
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-28 DOI: 10.1007/s10856-023-06717-3
Bárbara Araújo dos Reis, Natalia Da Ponte Leguizamón, Yumi Chokyu Del Rey, Leandro Fernandes, Cássio do Nascimento, Luis Geraldo Vaz

High implant survival rates have been achieved in recent decades due to continual modifications in implant design and surface topography, however there is still an ongoing quest to control peri-implant bone loss. The objective of this work was to develop Ti-35Nb-7Zr-5Ta (TNZT) alloys, perform physicochemical and morphological characterization of their surface modified by electrolytic oxidative plasma technique with ions related to osseointegration and lastly evaluate bacterial colonization in vitro. Three groups were evaluated: C group (polished TNZT), CaP group (sodium β glycerophosphate + calcium acetate) and Mg group (magnesium acetate). Before and after anodizing the surfaces, physicochemical and morphological analyses were performed: scanning electron microscopy with field emission gun (FEG-SEM), energy dispersion spectroscopy (EDS), X-ray diffraction (DRX), wettability (goniometer) and roughness (rugometer). Controlled and treated specimens were contaminated with unstimulated saliva collected from 10 healthy volunteers. Then, biofilm samples were collected and up to 35 microbial species, including commensal and pathogenic microorganisms, were identified and quantified by the Checkerboard DNA-DNA Hybridization method. The CaP group modified the surface morphology in the form of pores, while the Mg group modified it in the form of flakes. The contact angle was significantly smaller in the CaP group. The average roughness was higher in the CaP and Mg groups. A smaller total amount of bacteria was identified in the Mg group and relevant differences were found in the microbial profile associated with different surface treatments. Therefore, considering the microbiological profile and for the prevention of peri-implantitis, the Mg group presented more satisfactory and encouraging results for the manufacture of dental implants

Graphical Abstract

近几十年来,由于种植体设计和表面形貌的不断改进,种植体的成活率很高,然而,控制种植体周围骨丢失仍然是一个持续的探索。本工作的目的是开发Ti-35Nb-7Zr-5Ta (TNZT)合金,通过电解氧化等离子体技术对其表面进行与骨整合相关的离子修饰,进行物理化学和形态学表征,最后评估细菌在体外的定植。分为三组:C组(抛光TNZT)、CaP组(β甘油磷酸钠+醋酸钙)和Mg组(醋酸镁)。在阳极氧化前后,对表面进行了物理化学和形态分析:用场发射枪扫描电子显微镜(fg - sem)、能量色散光谱(EDS)、x射线衍射(DRX)、润湿性(角计)和粗糙度(粗糙度计)。对照和处理的标本被10名健康志愿者收集的未刺激唾液污染。然后,采集生物膜样品,采用棋盘DNA-DNA杂交法对35种微生物进行鉴定和定量,包括共生微生物和致病微生物。CaP组以孔隙形式修饰表面形貌,Mg组以薄片形式修饰表面形貌。CaP组接触角明显减小。CaP组和Mg组的平均粗糙度较高。Mg组的细菌总数较少,不同表面处理的微生物分布也存在相关差异。因此,从微生物学特征和预防种植周炎的角度考虑,Mg组在种植体的制造中表现出更令人满意和令人鼓舞的结果
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引用次数: 2
Microstructural, biocompatibility and mechanical investigation of MgHAp and AgHAp: Comparative report MgHAp和AgHAp的显微结构、生物相容性和力学研究:比较报告
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-28 DOI: 10.1007/s10856-023-06725-3
Anuradha Mahanty, Deep Shikha

It is imperative to investigate the effect of addition of different size metallic ions in HAp and study the changes in biocompatibility and mechanical properties. Silver and magnesium ions are two vital ions needed in our body. Silver ions are known to inhibit the microbes, while magnesium ions are known to increase the mechanical properties. The present study reports the comparative properties of MgHAp and AgHAp synthesised by sol-gel wet chemical method. Changes in the morphology, phase analysis, corrosion resistance, dielectric properties, hardness and the thrombus behaviour of HAp doped Ag and Mg ions has been investigated. In this work, we have presented a comparative study of both the metal doped ionsto find which of the ions and which weight percent of the ions can be best suited to be incorporated into the HAp matrix for hard tissue implants. All wt% AgHAp showed the better corrosion resistance than all the MgHAp samples. However, MgHAp showed higher value of hardness in comparison to AgHAp samples. The mechanical strength was found to increase with the increase in Mg wt% in MgHAp but for AgHAp the hardness value decreased with increase in the concentration. The impedance and dielectric loss decreased with increasing frequency for both the samples. Both the ion doped hydroxyapatite showed moderate clotting behaviour as compared to pure HAp. But 2 wt% MgHAp and 4 wt% AgHAp showed better thrombogenic behaviour.

研究不同尺寸金属离子的加入对HAp的影响,研究其生物相容性和力学性能的变化是十分必要的。银离子和镁离子是我们身体所需要的两种重要离子。众所周知,银离子可以抑制微生物,而镁离子可以提高机械性能。本研究报道了溶胶-凝胶湿化学法合成MgHAp和AgHAp的性能比较。研究了掺杂Ag和Mg离子的形貌、物相分析、耐蚀性、介电性能、硬度和血栓行为的变化。在这项工作中,我们提出了一种金属掺杂离子的比较研究,以发现哪种离子和哪种离子的重量百分比最适合纳入硬组织植入物的HAp基质中。所有wt% AgHAp样品的耐腐蚀性均优于所有MgHAp样品。然而,MgHAp样品的硬度值高于AgHAp样品。MgHAp的机械强度随Mg wt%的增加而增加,而AgHAp的硬度随Mg wt%的增加而降低。两种样品的阻抗和介电损耗均随频率的增加而减小。与纯羟基磷灰石相比,两种离子掺杂羟基磷灰石均表现出适度的凝血行为。但2 wt% MgHAp和4 wt% AgHAp表现出更好的血栓形成行为。
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引用次数: 1
An autologous blood-derived patch as a hemostatic agent: evidence from thromboelastography experiments and a porcine liver punch biopsy model 自体血源性贴片作为止血剂:来自血栓弹性成像实验和猪肝穿刺活检模型的证据
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-19 DOI: 10.1007/s10856-023-06726-2
Morten P. R. Eskildsen, Otto Kalliokoski, Marie Boennelycke, Rasmus Lundquist, Annette Settnes, Ellen Loekkegaard

Perioperative bleeding is a common complication in surgeries that increases morbidity, risk of mortality, and leads to increased socioeconomic costs. In this study we investigated a blood-derived autologous combined leukocyte, platelet, and fibrin patch as a new means of activating coagulation and maintaining hemostasis in a surgical setting. We evaluated the effects of an extract derived from the patch on the clotting of human blood in vitro, using thromboelastography (TEG). The autologous blood-derived patch activated hemostasis, seen as a reduced mean activation time compared to both non-activated controls, kaolin-activated samples, and fibrinogen/thrombin-patch-activated samples. The accelerated clotting was reproducible and did not compromise the quality or stability of the resulting blood clot. We also evaluated the patch in vivo in a porcine liver punch biopsy model. In this surgical model we saw 100% effective hemostasis and a significant reduction of the time-to-hemostasis, when compared to controls. These results were comparable to the hemostatic properties of a commercially available, xenogeneic fibrinogen/thrombin patch. Our findings suggest clinical potential for the autologous blood-derived patch as a hemostatic agent.

Graphical Abstract

围手术期出血是一种常见的手术并发症,它增加了发病率、死亡率风险,并导致社会经济成本的增加。在这项研究中,我们研究了血液来源的自体联合白细胞、血小板和纤维蛋白贴片作为一种在外科环境中激活凝血和维持止血的新手段。我们使用血栓弹性成像(TEG)评估了从贴片中提取的提取物对体外凝血的影响。自体血源性贴片激活止血,与未激活的对照、高岭土激活的样品和纤维蛋白原/凝血酶贴片激活的样品相比,平均激活时间缩短。加速凝血是可重复的,并且不会损害所产生的血凝块的质量或稳定性。我们还在猪肝穿刺活检模型中对该贴片进行了体内评估。在这个手术模型中,与对照组相比,我们看到100%的有效止血和明显缩短的止血时间。这些结果与市售的异种纤维蛋白原/凝血酶贴片的止血性能相当。我们的发现提示了自体血源性贴片作为止血剂的临床潜力。图形抽象
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引用次数: 0
Cyclic pressure induced decellularization of porcine descending aortas 循环压力诱导猪降主动脉脱细胞
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-19 DOI: 10.1007/s10856-023-06723-5
Barbara Messner, Maximilian Grab, Linda Grefen, Günther Laufer, Christian Hagl, Fabian König

The demand for decellularized xenogeneic tissues used in reconstructive heart surgery has increased over the last decades. Complete decellularization of longer and tubular aortic sections suitable for clinical application has not been achieved so far. The present study aims at analyzing the effect of pressure application on decellularization efficacy of porcine aortas using a device specifically designed for this purpose. Fresh porcine descending aortas of 8 cm length were decellularized using detergents. To increase decellularization efficacy, detergent treatment was combined with pressure application and different treatment schemes. Quantification of penetration depth as well as histological staining, scanning electron microscopy, and tensile strength tests were used to evaluate tissue structure. In general, application of pressure to aortic tissue does neither increase the decellularization success nor the penetration depth of detergents. However, it is of importance from which side of the aorta the pressure is applied. Application of intermittent pressure from the adventitial side does significantly increase the decellularization degree at the intimal side (compared to the reference group), but had no influence on the penetration depth of SDC/SDS at both sides. Although the present setup does not significantly improve the decellularization success of aortas, it is interesting that the application of pressure from the adventitial side leads to improved decellularization of the intimal side. As no adverse effects on tissue structure nor on mechanical properties were observed, optimization of the present protocol may potentially lead to complete decellularization of larger aortic segments.

Graphical Abstract

在过去的几十年里,心脏重建手术中对脱细胞异种组织的需求有所增加。适合临床应用的较长和管状主动脉切片的完全脱细胞尚未实现。本研究旨在使用专门设计的装置分析压力应用对猪主动脉脱细胞效果的影响。用洗涤剂对8厘米长的新鲜猪降主动脉进行脱细胞处理。为了提高脱细胞效果,将去污剂处理与压力施加和不同的处理方案相结合。通过穿刺深度定量、组织学染色、扫描电镜和拉伸强度测试来评估组织结构。一般来说,对主动脉组织施加压力既不能增加脱细胞的成功率,也不能增加洗涤剂的渗透深度。然而,从主动脉的哪一侧施加压力是很重要的。与对照组相比,外膜侧施加间歇性压力确实显著增加了内膜侧的脱细胞程度,但对两侧SDC/SDS的渗透深度没有影响。虽然目前的设置并不能显著提高主动脉的脱细胞成功率,但有趣的是,从动脉外侧施加压力可以改善动脉内膜侧的脱细胞。由于没有观察到对组织结构和力学性能的不利影响,因此本方案的优化可能会导致更大的主动脉段完全脱细胞。图形抽象
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引用次数: 0
RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy RGD肽修饰的红细胞膜功能化仿生纳米颗粒用于溶栓治疗
IF 3.7 3区 医学 Q1 Biochemistry, Genetics and Molecular Biology Pub Date : 2023-04-12 DOI: 10.1007/s10856-023-06719-1
Zichen Xu, Jinxia Huang, Tao Zhang, Wenfeng Xu, Xiaoling Liao, Yi Wang, Guixue Wang

In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a “core-shell” structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis.

Graphical Abstract

近年来,制备靶向治疗血栓的纳米给药系统已成为研究热点。在本研究中,我们打算构建一种靶向治疗血栓的仿生纳米药物。选择聚乳酸-羟基乙酸(PLGA)作为纳米载体材料。然后,采用双乳化溶剂蒸发法将尿激酶和全氟正戊烷(PFP)共负载到PLGA中,制备相变纳米PPUNPs。随后,将RGD肽修饰的红细胞膜(RBCM)涂覆在PPUNPs表面,制备仿生纳米药物载体(RGD-RBCM@PPUNPs)。制备的RGD-RBCM@PPUNPs具有“核-壳”结构,具有良好的分散性,继承了红细胞的膜蛋白组成。在超声刺激下,装载的尿激酶可以快速释放。体外细胞实验表明RGD-RBCM@PPUNPs具有良好的血液相容性和细胞相容性。由于包裹有RGD-RBC膜,RGD-RBCM@PPUNPs可以有效抑制巨噬细胞的摄取。此外,RGD-RBCM@PPUNPs在体外具有较好的溶栓功能。结果表明,这种仿生纳米药物为血栓形成的靶向治疗提供了一种很有前景的治疗策略。图形抽象
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Journal of Materials Science: Materials in Medicine
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