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Hemostatic Shape Memory Polymer Foams With Improved Survival in a Lethal Traumatic Hemorrhage Model 止血形状记忆聚合物泡沫提高致死性创伤出血模型的存活率
Pub Date : 2021-10-01 DOI: 10.2139/ssrn.3864497
Henry T. Beaman, Ellen Shepherd, J. Satalin, S. Blair, H. Ramcharran, S. Serinelli, L. Gitto, Katheryn Shi Dong, David Fikhman, G. Nieman, S. Schauer, M. B. Monroe
Although there are many hemostatic agents available for use on the battlefield, uncontrolled hemorrhage is still the primary cause of preventable death. Current hemostatic dressings include QuikClot® Combat Gauze (QCCG) and XStat®, which have inadequate success in reducing mortality. To address this need, a new hemostatic material was developed using shape memory polymer (SMP) foams, which demonstrate biocompatibility, rapid clotting, and shape recovery to fill the wound site. SMP foam hemostatic efficacy was examined in a lethal, noncompressible porcine liver injury model over 6 hours following injury. Wounds were packed with SMP foams, XStat, or QCCG and compared in terms of time to bleeding cessation, total blood loss, and animal survival. The hemostatic material properties and in vitro blood interactions were also characterized. SMP foams decreased blood loss and active bleeding time in comparison with XStat and QCCG. Most importantly, SMP foams increased the 6-hour survival rate by 50% and 37% (vs. XStat and QCCG, respectively) with significant increases in survival times. Based upon in vitro characterizations, this result is attributed to the low stiffness and shape filling capabilities of SMP foams. This study demonstrates that SMP foams have promise for improving upon current clinically available hemostatic dressings and that hemostatic material properties are important to consider in designing devices for noncompressible bleeding control.
虽然有许多止血剂可用于战场,但不受控制的出血仍然是可预防死亡的主要原因。目前的止血敷料包括QuikClot®战斗纱布(QCCG)和XStat®,它们在降低死亡率方面没有足够的成功。为了满足这一需求,一种使用形状记忆聚合物(SMP)泡沫的新型止血材料被开发出来,这种材料具有生物相容性、快速凝血和形状恢复能力,可以填充伤口部位。在致死性、不可压缩性猪肝损伤模型中观察SMP泡沫止血效果。伤口用SMP泡沫、XStat或QCCG填充,并比较止血时间、总失血量和动物存活率。止血材料的性能和体外血液相互作用也进行了表征。与XStat和QCCG相比,SMP泡沫减少了失血量和活动出血时间。最重要的是,SMP泡沫使6小时存活率提高了50%和37%(分别与XStat和QCCG相比),存活时间显著增加。基于体外表征,这一结果归因于SMP泡沫的低刚度和形状填充能力。这项研究表明,SMP泡沫有望改善目前临床可用的止血敷料,并且在设计不可压缩出血控制装置时,止血材料的性能是重要的考虑因素。
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引用次数: 30
Cochlear Implant-Based Electric-Acoustic Stimulation Modulates Neural Stem Cell-Derived Neural Regeneration 基于人工耳蜗的电声刺激调节神经干细胞衍生的神经再生
Pub Date : 2021-09-29 DOI: 10.2139/ssrn.3762217
Rongrong Guo, Menghui Liao, Xiaofeng Ma, Yangnan Hu, X. Qian, M. Xiao, Xia Gao, R. Chai, Mingliang Tang
Cochlear implantation is considered to be the best therapeutic method for profound sensorineural hearing loss, but insufficient numbers of functional spiral ganglion neurons hinder the clinical effects of cochlear implantation. Stem cell transplantation has the potential to provide novel strategies for spiral ganglion neuron regeneration after injury. However, some obstacles still need to be overcome, such as low survival and uncontrolled differentiation. Several novel technologies show promise for modulating neural stem cell behaviors to address these issues. Here, a device capable of electrical stimulation was designed by combining a cochlear implant with a graphene substrate. Neural stem cells (NSCs) were cultured on the graphene substrate and subjected to electrical stimulation transduced from sound waves detected by the cochlear implant. Cell behaviors were studied, and this device showed good biocompatibility for NSCs. More importantly, electric-acoustic stimulation with higher frequencies and amplitudes induced NSC death and apoptosis, and electric-acoustic stimulation could promote NSCs to proliferate and differentiate into neurons only when low-frequency stimulation was supplied. The present study provides experimental evidence for understanding the regulatory role of electric-acoustic stimulation on NSCs and highlights the potentials of the above-mentioned device in stem cell therapy for hearing loss treatment.
人工耳蜗植入术被认为是治疗重度感音神经性听力损失的最佳方法,但功能性螺旋神经节神经元数量不足阻碍了人工耳蜗植入术的临床效果。干细胞移植有可能为损伤后螺旋神经节神经元的再生提供新的策略。然而,仍有一些障碍需要克服,如低存活率和不受控制的分化。一些新技术显示了调节神经干细胞行为来解决这些问题的希望。本研究通过将人工耳蜗与石墨烯衬底结合,设计了一种能够进行电刺激的装置。神经干细胞(NSCs)在石墨烯基质上培养,并接受由人工耳蜗检测到的声波传导的电刺激。实验结果表明,该装置具有良好的生物相容性。更重要的是,更高频率和振幅的电声刺激可诱导NSC死亡和凋亡,并且只有在低频刺激下,电声刺激才能促进NSCs增殖并向神经元分化。本研究为理解电声刺激对NSCs的调控作用提供了实验依据,并突出了上述装置在听力损失干细胞治疗中的潜力。
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引用次数: 9
Magnetic Mesoporous Embolic Microspheres in Transcatheter Arterial Chemoembolization for Liver Cancer 磁性介孔栓塞微球在肝癌经导管动脉化疗栓塞中的应用
Pub Date : 2021-05-31 DOI: 10.2139/ssrn.3757902
Li Liu, Xianxian Liang, Xiangxian Xu, Xiang Zhang, Jun Wen, Kun Chen, Xiaodan Su, Zhaogang Teng, Guangming Lu, Jian Xu
Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug loading, and imaging properties have not yet been constructed. Herein, we report a new magnetic mesoporous embolic microsphere that can simultaneously be loaded with doxorubicin (Dox), block vessels, and be observed by magnetic resonance imaging (MRI). The microspheres were prepared by decorating magnetic polystyrene/Fe3O4 particles with mesoporous organosilica microparticles (denoted as PS/Fe3O4@MONs). The PS/Fe3O4@MONs were uniformly spherical and large (50 μm), with a high specific surface area, uniform mesopores, and a Dox loading capacity of 460.8 μg mg-1. Dox-loaded PS/Fe3O4@MONs (PS/Fe3O4@MON@Dox) effectively inhibited liver cancer cell growth. A VX2 rabbit liver tumor model was constructed to study the efficacy of TACE with PS/Fe3O4@MON@Dox. In vivo, PS/Fe3O4@MON@Dox could be smoothly delivered through an arterial catheter to achieve chemoembolization. Moreover, PS/Fe3O4@MON@Dox and residual tumor parenchyma could be distinguished on MRI, which is of great significance for evaluating the efficacy of TACE. Histopathology showed that PS/Fe3O4@MON@Dox could be deposited in the tumor vessels, completely blocking the blood supply. Overall, PS/Fe3O4@MON@Dox showed good drug loading, embolization and imaging performance as well as potential for use in TACE. STATEMENT OF SIGNIFICANCE: : Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug-loading, and imaging properties have not yet been constructed. In this work, we prepared magnetic mesoporous microspheres as a new embolic agent that can simultaneously load doxorubicin (Dox), block blood vessels and enable magnetic resonance imaging. Overall, this new embolic microsphere-mediated TACE strategy for liver cancer showed good therapeutic effects, and the PS/Fe3O4@MON@Dox embolic microspheres provide a new avenue for improving the efficacy of TACE for liver cancer and postoperative evaluation.
经导管动脉化疗栓塞(TACE)是肝癌的主要治疗方法。虽然许多栓塞剂已被用于TACE,但结合栓塞、载药和成像特性的栓塞剂尚未构建。在此,我们报道了一种新的磁性介孔栓塞微球,它可以同时装载阿霉素(Dox),阻塞血管,并通过磁共振成像(MRI)观察。用介孔有机二氧化硅微粒(PS/Fe3O4@MONs)修饰磁性聚苯乙烯/Fe3O4颗粒制备微球。PS/Fe3O4@MONs呈均匀球形,尺寸大(50 μm),比表面积高,介孔均匀,载Dox能力为460.8 μg mg-1。负载dox的PS/Fe3O4@MONs (PS/Fe3O4@MON@Dox)有效抑制肝癌细胞生长。建立VX2兔肝肿瘤模型,研究PS/Fe3O4@MON@Dox对TACE的作用。在体内,PS/Fe3O4@MON@Dox可以通过动脉导管顺利输送,实现化疗栓塞。MRI可区分PS/Fe3O4@MON@Dox和残余肿瘤实质,对评价TACE疗效具有重要意义。组织病理学显示,PS/Fe3O4@MON@Dox可沉积在肿瘤血管中,完全阻断血液供应。总体而言,PS/Fe3O4@MON@Dox表现出良好的载药、栓塞和成像性能,以及在TACE中的应用潜力。意义声明:经导管动脉化疗栓塞(TACE)是肝癌的主要治疗方法。虽然许多栓塞剂已被用于TACE,但结合栓塞、载药和成像特性的栓塞剂尚未构建。在这项工作中,我们制备了磁性介孔微球作为一种新的栓塞剂,可以同时加载阿霉素(Dox),阻塞血管并实现磁共振成像。总的来说,这种新的栓塞微球介导肝癌TACE策略显示出良好的治疗效果,PS/Fe3O4@MON@Dox栓塞微球为提高肝癌TACE疗效和术后评价提供了新的途径。
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引用次数: 11
Examining How Different Carbon Entry Point Affects Recombinant Protein Production from Ethylene Glycol in Bacillus Subtilis 探讨枯草芽孢杆菌中不同碳入口点对乙二醇生产重组蛋白的影响
Pub Date : 2021-03-29 DOI: 10.2139/ssrn.3814484
Wenfa Ng
Recombinant protein production is the first application task for nascent genetic engineering efforts in 1970s. Since then, a variety of basic science and process engineering approaches have been used in improving recombinant protein production. Given that protein production could serve as marker for how well rewired metabolism is functioning, possibility exists in using it to highlight the most suitable pathway for assimilating a particular unconventional substrate. To this end, different pathways with different carbon entry point in central carbon metabolism could be constructed, with fluorescence of a green fluorescent protein as readout. Good carbon entry point should ideally lead to even distribution of substrate flux to all precursors feeding amino acid synthesis, and should result in strong fluorescence intensity and high protein production. This perspective critically examines the literature for prior work on the above hypothesis in relation to utilization of ethylene glycol by Bacillus subtilis. A literature review suggests that the hypothesis is novel, and provides additional information that modulation of global regulatory protein (transcription factor) may serve as ancillary factors promoting high recombinant protein production.
重组蛋白的生产是20世纪70年代新生的基因工程努力的第一个应用任务。从那时起,各种基础科学和工艺工程方法被用于改善重组蛋白的生产。考虑到蛋白质的产生可以作为重新连接代谢功能的标志,利用它来突出吸收特定非常规底物的最合适途径是存在可能性的。为此,可以构建中心碳代谢不同碳入口点的不同途径,以绿色荧光蛋白的荧光为读出。理想情况下,良好的碳入口点应导致底物通量均匀分布到所有用于氨基酸合成的前体,并应导致强荧光强度和高蛋白质产量。这一观点批判性地检查了文献先前的工作对上述假设有关利用乙二醇的枯草芽孢杆菌。文献综述表明,这一假设是新颖的,并提供了额外的信息,即全局调节蛋白(转录因子)的调节可能是促进高重组蛋白生产的辅助因素。
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引用次数: 0
Printable Smart 3D Architectures of Regenerated Silk on Poly(3- Hydroxybutyrate-Co-3-Hydroxyvalerate) 聚(3-羟丁酸酯- co -3-羟戊酸酯)再生丝可打印的智能3D结构
Pub Date : 2021-03-15 DOI: 10.2139/ssrn.3805241
S. B. Bon, Irene Chiesa, D. Morselli, M. D. Esposti, P. Fabbri, C. De Maria, Tommaso Foggi Viligiardi, A. Morabito, G. Giorgi, L. Valentini
In this study, we report the fabrication of two different three-dimensional (3D) architectures of regenerated silk (RS) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with embedded functionalities. 3D printed cylinders with an internal layer of PHBV and an external of calcium ions (Ca++) or potassium nitrate (KNO3) modified RS were designed to control the radial shrinkage, water uptake and compression strength. Such cylinders were then used as sutureless thermoresponsive clips, measuring the bursting resistance once applied on an anastomized porcine intestine. Experimental data are supported by finite element simulations that model the tube contraction, demonstrating the possibility to program the shape-changing behavior of 3D printed structures. Printing RS on PHBV, we obtained responsive 3D grids to external force with self-powering properties. The synergic effect obtained by combining materials on appropriate architectures paves the way to potential clinical applications ranging from monitoring of vital signs to sutureless sealant patches.
在这项研究中,我们报道了再生丝(RS)和具有嵌入功能的聚(3-羟基丁酸-co-3-羟基戊酸酯)(PHBV)的两种不同的三维(3D)结构的制备。设计了3D打印圆柱体,内层为PHBV,外部为钙离子(Ca++)或硝酸钾(KNO3)改性RS,以控制径向收缩率、吸水率和抗压强度。然后将这些圆柱体用作无缝合线的热响应夹,测量一旦应用于吻合的猪肠上的破裂阻力。实验数据由模拟管收缩的有限元模拟支持,证明了对3D打印结构的形状变化行为进行编程的可能性。在PHBV上打印RS,我们获得了具有自供电特性的对外力响应的3D网格。通过在适当的结构上组合材料获得的协同效应为潜在的临床应用铺平了道路,从监测生命体征到无缝合线的密封剂贴片。
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引用次数: 0
Efficacy of Graphene Nanosheets on the Plasma Sprayed Hydroxyapatite Coating: Improved Strength, Toughness and In-Vitro Bioperformance With Osteoblast 石墨烯纳米片在等离子喷涂羟基磷灰石涂层上的效果:提高成骨细胞的强度、韧性和体外生物性能
Pub Date : 2021-02-14 DOI: 10.2139/ssrn.3805229
Yao Chen, Jia Ren, Yufeng Sun, Weiwei Liu, Xiaolong Lu, S. Guan
Abstract Graphene nanosheet (GNS) reinforced HA coating on Ti6Al4V substrate, fabricated using plasma spray, was developed for biomedical applications. Microstructural observation corroborated that the adding GNSs homogeneously distributed in the GNS/HA coating with typical lamellar structure featured by GNSs acting as binder between the discrete HA splats. Meanwhile, GNSs were observed to get in direct contact with HA matrix and form a clean GNS-HA interface without interfacial product. Results of various indentation tests showed simultaneous improvement in both indentation yield strength (~379 MPa) and fracture toughness (0.78 ± 0.17 MPam1/2), mainly attributing to synergetic toughening and strengthening mechanisms associated with the adding GNSs such as load transfer, GNS pull-out, inter-layer sliding of a GNS, crack branching, GNS bridging and crack deflection. In addition, the GNS/HA coating exhibited improved biocompatible with MG-63 cell in terms of its attachment, adhesion strength, proliferation and differentiation. Hence, the GNS/HA composite coating with improved strength, toughness and enhanced biocompatibility makes it a promising candidate for bone regeneration and implantation.
采用等离子喷涂技术在Ti6Al4V基体上制备了石墨烯纳米片增强羟基磷灰石涂层,并将其应用于生物医学领域。显微组织观察证实,添加的GNSs均匀分布在GNS/HA涂层中,具有典型的片层结构,GNSs在分散的HA薄片之间起到粘结剂作用。同时,观察到GNSs与HA矩阵直接接触,形成干净的GNS-HA界面,无界面产物。压痕屈服强度(~379 MPa)和断裂韧性(0.78 ± 0.17 MPam1/2)同时提高,这主要是由于添加GNS的载荷传递、GNS拉出、GNS层间滑动、裂纹分支、GNS桥接和裂纹偏转等协同增韧强化机制所致。此外,GNS/HA涂层与MG-63细胞在附着、粘附强度、增殖和分化等方面均表现出较好的生物相容性。因此,GNS/HA复合涂层具有较好的强度、韧性和生物相容性,是骨再生和骨植入的理想材料。
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引用次数: 9
Damage Tolerance and Toughness of Elderly Human Femora 老年人股骨的损伤容忍度和韧性
Pub Date : 2021-01-14 DOI: 10.2139/ssrn.3726342
S. Martelli, M. Giorgi, Enrico Dall' Ara, E. Perilli
Observations of elastic instability of trabecular bone cores supported the analysis of cortical thickness for predicting bone fragility of the hip in people over 60 years of age. Here, we falsified the hypothesis that elastic instability causes minimal energy fracture by analyzing with a micrometric resolution the deformation and fracture behavior of entire femora. Femur specimens were obtained from elderly women aged between 66 - 80 years. Microstructural images of the proximal femur where obtained under 3 - 5 progressively increased loading steps and after fracture. Bone displacements, strain, load bearing and energy absorption capacity were analyzed. Elastic instability of the cortex appeared at early loading stages in regions of peak compression. No elastic instability of trabecular bone was observed. The subchondral bone displayed local crushing in compression at early loading steps and progressed to 8 - 16% compression before fracture. The energy absorption capacity was proportional to the displacement. Stiffness decreased to near-zero values before fracture. Three-fourth of the fracture energy (10.2 - 20.2 J) was dissipated in the final 25% force increment. Fracture occurred in regions of peak tension and shear, adjacent to the location of peak compression, appearing immediately before fracture. Minimal permanent deformation was visible along the fracture surface. Elastic instability modulates the interaction between cortical and trabecular bone promoting an elastically stable fracture behavior of the femur organ, load bearing capacity, toughness, and damage tolerance. These findings will advance current methods for predicting hip fragility.
对骨小梁核心弹性不稳定性的观察支持了皮质厚度预测60岁以上人群髋部骨脆弱性的分析。在这里,我们通过微观分辨率分析整个股骨的变形和骨折行为,证伪了弹性不稳定性导致最小能量骨折的假设。股骨标本取自66 - 80岁的老年妇女。股骨近端显微结构图像是在3 - 5加载步骤逐渐增加和骨折后获得的。分析了骨位移、应变、承载和能量吸收能力。皮质弹性失稳出现在加载初期的峰值压缩区。未见骨小梁弹性失稳。软骨下骨在早期加载阶段表现为局部挤压,并在骨折前发展到8 - 16%的压缩。能量吸收能力与位移成正比。断裂前刚度降至接近零值。四分之三的断裂能(10.2 - 20.2 J)在最后25%的力增量中耗散。断裂发生在张力和剪切峰值区域,与压缩峰值位置相邻,在断裂前立即出现。沿断裂面可见最小的永久变形。弹性不稳定性调节皮质骨和骨小梁之间的相互作用,促进股骨器官的弹性稳定骨折行为、承载能力、韧性和损伤容忍度。这些发现将推动目前预测髋关节脆弱性的方法。
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引用次数: 8
Effects of Modified Starch on Morphology, Properties and Biodegradation of Thermoplastic Cassava Starch and Pbat Blown Films for Food Packaging 变性淀粉对热塑性木薯淀粉及食品包装用Pbat吹膜形态、性能及生物降解的影响
Pub Date : 2021-01-01 DOI: 10.2139/ssrn.3936308
Phanwipa Wongphan, Theeraphorn Panrong, N. Harnkarnsujarit
Modified starch enhanced the compatibility and modified the properties of thermoplastic starch (TPS) and polybutylene adipate terephthalate (PBAT) biodegradable films. Native (NS), acetylated (AS), octenyl-succinated (OS) and hydroxypropylated (HS) starch were compounded with PBAT via extrusion. PBAT/TPS (40/60 and 50/50 ratios) blend films were produced by blown-film extrusion and characterized for morphology, crystallinity, thermomechanical properties, mechanical and barrier properties. Topographic and scanning electron micrographs showed diverse dispersion and morphologies of starch granules depending on hydrophobicity that governed interface exposure between incompatible polymers. Hydrophilic starch formed phase separated fibrous-like networks entangled in PBAT at higher TPS ratios. Hydrophobic OS starch improved compatibility and interaction with PBAT, greatly modifying mechanical and barrier properties (82-89%). TPS slightly increased α-relaxation temperature and modified arrangements of aromatic structures in PBAT, involving C-H and C-O bonding, subsequently influencing crystallinity of PBAT and the starch phase. Biodegradation of the blend films was dependent on hydrophilicity of starch, giving the fastest degradation in NS and HS. Findings indicated that hydrophobically modified starch improved compatibility with PBAT for biodegradable packaging, while film properties were highly dependent on the morphology of blend matrices.
改性淀粉增强了热塑性淀粉(TPS)与聚己二酸丁二酯(PBAT)生物降解膜的相容性,并对其性能进行了改性。采用挤压法制备了天然淀粉(NS)、乙酰化淀粉(AS)、辛烯基琥珀化淀粉(OS)和羟丙基淀粉(HS)。采用吹膜挤出法制备了PBAT/TPS(40/60和50/50)共混薄膜,并对其形貌、结晶度、热机械性能、力学性能和阻隔性能进行了表征。形貌和扫描电镜显示淀粉颗粒的分散和形态不同,这取决于不相容聚合物之间的界面暴露的疏水性。在较高的TPS比率下,亲水淀粉在PBAT中形成相分离的纤维状网络。疏水OS淀粉改善了与PBAT的相容性和相互作用,极大地改变了力学和屏障性能(82-89%)。TPS略微提高了PBAT的α-弛豫温度,并改变了PBAT中芳香族结构的排列,包括C-H和C-O键,从而影响了PBAT和淀粉相的结晶度。共混膜的生物降解取决于淀粉的亲水性,在NS和HS中降解速度最快。研究结果表明,疏水改性淀粉改善了与PBAT的相容性,可用于生物降解包装,而膜的性能高度依赖于共混基质的形态。
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引用次数: 0
Insights into Oxidative Stress in Bone Tissue and Novel Challenges for Biomaterials 洞察骨组织氧化应激和生物材料的新挑战
Pub Date : 2020-12-18 DOI: 10.2139/ssrn.3751572
G. Cerqueni, A. Scalzone, C. Licini, P. Gentile, M. Mattioli-Belmonte
The presence of Reactive Oxygen Species (ROS) in bone can influence resident cells behaviour as well as the extra-cellular matrix composition and the tissue architecture. Aging, in addition to excessive overloads, unbalanced diet, smoking, predisposing genetic factors, lead to an increase of ROS and, if it is accompanied with an inappropriate production of scavengers, promotes the generation of oxidative stress that encourages bone catabolism. Furthermore, bone injuries can be triggered by numerous events such as road and sports accidents or tumour resection. Although bone tissue possesses a well-known repair and regeneration capacity, these mechanisms are inefficient in repairing large size defects and bone grafts are often necessary. ROS play a fundamental role in response after the implant introduction and can influence its success. This review provides insights on the mechanisms of oxidative stress generated by an implant in vivo and suitable ways for its modulation. The local delivery of active molecules, such as polyphenols, enhanced bone biomaterial integration evidencing that the management of the oxidative stress is a target for the effectiveness of an implant. Polyphenols have been widely used in medicine for cardiovascular, neurodegenerative, bone disorders and cancer, thanks to their antioxidant and anti-inflammatory properties. In addition, the perspective of new smart biomaterials and molecular medicine for the oxidative stress modulation in a programmable way, by the use of ROS responsive materials or by the targeting of selective molecular pathways involved in ROS generation, will be analysed and discussed critically.
活性氧(ROS)在骨中的存在可以影响驻留细胞的行为以及细胞外基质组成和组织结构。衰老,再加上过度负荷、不平衡的饮食、吸烟、易感的遗传因素,都会导致活性氧增加,如果伴随着不适当的清除剂产生,就会促进氧化应激的产生,从而促进骨分解代谢。此外,骨损伤可由许多事件引发,如道路和运动事故或肿瘤切除。尽管骨组织具有众所周知的修复和再生能力,但这些机制在修复大尺寸缺陷时效率低下,骨移植往往是必要的。活性氧在植入物引入后的反应中起着至关重要的作用,并影响植入物的成功。本文综述了体内植入物产生氧化应激的机制及其调节方法。活性分子(如多酚)的局部传递增强了骨生物材料的整合,证明氧化应激的管理是植入物有效性的目标。由于其抗氧化和抗炎特性,多酚已广泛应用于心血管、神经退行性疾病、骨骼疾病和癌症的医学中。此外,新的智能生物材料和分子医学的观点,以可编程的方式进行氧化应激调节,通过使用ROS反应材料或通过选择性分子途径参与ROS的产生,将进行批判性的分析和讨论。
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引用次数: 32
Proangiogenic Collagen Binding Glycan Therapeutic Promotes Endothelial Cell Health: Potential Application for the Treatment of Ischemic Wounds 促血管生成胶原结合聚糖治疗促进内皮细胞健康:在缺血性伤口治疗中的潜在应用
Pub Date : 2020-12-11 DOI: 10.2139/ssrn.3746791
Tanaya Walimbe, Tima Dehghani, A. Casella, Jenny B. Lin, Aijun Wang, A. Panitch
Peripheral artery disease and endothelial cell dysfunction due to diabetes contribute to impaired neovascularization and poor healing of ischemic wounds. Treatments addressing this underlying ischemia that remain effective in the highly proteolytic diabetic wound environment are urgently needed to increase the rate of wound healing and reduce diabetes-related lower-limb amputations. Our lab has previously designed a collagen-targeted glycan therapeutic (DS-SILY) capable of protecting collagen-based scaffolds from matrix metalloproteinase (MMP) mediated degradation. Building upon this targeted technology, we designed the next generation glycan therapy, termed LXW7-DS-SILY (LDS), to also contain proangiogenic capabilities. By exploiting αvβ3 integrin-mediated VEGF signaling using our previously identified αvβ3 integrin targeted peptide (LXW7), we propose an alternative strategy to overcome shortcomings of traditional growth factor therapy. In this study, we describe the synthesis and optimization of LDS variants and evaluate their angiogenic potential in vitro and in vivo. LDS displayed binding to collagen and endothelial cells. In vitro, the LDS variant with 6 LXW7 peptides increased endothelial cell proliferation, migration, and tubule formation through increased VEGFR2 phosphorylation compared to non-treated controls. In vivo in a chick chorioallantoic membrane (CAM) assay, LDS laden collagen hydrogels increased blood vessel formation by 43% in comparison to organism matched blank hydrogels. Overall, these findings demonstrate the potential of a robust proangiogenic targeted therapeutic for the treatment of ischemic diabetic wounds.
糖尿病引起的外周动脉疾病和内皮细胞功能障碍导致新生血管受损和缺血性伤口愈合不良。迫切需要在高度蛋白水解的糖尿病伤口环境中有效地治疗这种潜在的缺血,以提高伤口愈合率并减少糖尿病相关的下肢截肢。我们的实验室之前设计了一种胶原靶向聚糖治疗(ds - sicy),能够保护胶原基支架免受基质金属蛋白酶(MMP)介导的降解。基于这种靶向技术,我们设计了下一代多糖疗法,称为LXW7-DS-SILY (LDS),它也具有促进血管生成的能力。利用αvβ3整合素靶向肽(LXW7),利用αvβ3整合素介导的VEGF信号,我们提出了一种替代策略,以克服传统生长因子治疗的缺点。在这项研究中,我们描述了LDS变体的合成和优化,并评估了它们在体外和体内的血管生成潜力。LDS与胶原蛋白和内皮细胞结合。在体外,与未处理的对照组相比,具有6个LXW7肽的LDS变体通过增加VEGFR2磷酸化增加了内皮细胞的增殖、迁移和小管的形成。在鸡绒毛膜尿囊膜(CAM)实验中,与生物匹配的空白水凝胶相比,LDS填充的胶原水凝胶使血管形成增加了43%。总的来说,这些发现证明了一种强大的促血管生成靶向治疗缺血性糖尿病伤口的潜力。
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引用次数: 1
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Biomaterials eJournal
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