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LBL assembly of Ag@Ti3C2T X and chitosan on PLLA substrate to enhance antibacterial and biocompatibility 的LBL组件Ag@Ti3C2TX和壳聚糖在PLLA基质上增强抗菌性和生物相容性
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-31 DOI: 10.1088/1748-605X/ac62e7
Haibo Wang, A. Dong, K. Hu, Weiwei Sun, Jundong Wang, L. Han, L. Mo, Luhai Li, Wei Zhang, Yan Guo, Li Zhu, F. Cui, Yen Wei
Poly L-lactic acid (PLLA) is a non-toxic, biocompatible degradable polymer material with excellent mechanical properties after moulding. However, it faces challenges in the use of biomedical materials because of its intolerance to bacteria. Here, we use an easy-to-operate method to prepare a composite multilayer membrane: PLLA membrane was used as substrates to assemble positively charged chitosan and negatively charged Ag@MXene on the surface using the layer-by-layer (LBL) method. The assembly process was detected by fluorescein isothiocyanate-labelled chitosan and the thickness of the coating multilayer was also detected as 210.0 ± 12.1 nm for P-M membrane and 460.5 ± 26.5 nm for P-Ag@M membrane. The surface self-assembled multilayers exhibited 91.27% and 96.11% growth inhibition ratio against Escherichia coli and Staphylococcus aureus strains under 808 nm near-infrared laser radiation with a synergistic photothermal antibacterial effect. Furthermore, best biocompatibility of P-M and P-Ag@M membranes compare to PLLA membrane motivated us to further explore its application in biomedical materials.
聚L-乳酸(PLLA)是一种无毒、生物相容的可降解聚合物材料,成型后具有优异的力学性能。然而,由于其对细菌的不耐受性,它在生物医学材料的使用方面面临挑战。在这里,我们使用一种易于操作的方法来制备复合多层膜:以PLLA膜为基底组装带正电荷的壳聚糖和带负电荷的壳多糖Ag@MXene使用逐层(LBL)方法在表面上。用异硫氰酸荧光素标记的壳聚糖检测组装过程,P-M膜的多层涂层厚度为210.0±12.1nmP-Ag@M膜表面自组装多层膜在808nm近红外激光辐射下对大肠杆菌和金黄色葡萄球菌的生长抑制率分别为91.27%和96.11%,具有协同的光热抗菌作用。此外,P-M和P-Ag@M膜与PLLA膜的比较促使我们进一步探索其在生物医学材料中的应用。
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引用次数: 2
Graphene oxide encapsulated forsterite scaffolds to improve mechanical properties and antibacterial behavior 氧化石墨烯包裹镁橄榄石支架提高力学性能和抗菌性能
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-31 DOI: 10.1088/1748-605X/ac62e8
A. Najafinezhad, H. R. Bakhsheshi‐Rad, A. Saberi, A. Nourbakhsh, M. Daroonparvar, A. Ismail, S. Sharif, S. Ramakrishna, Yunqian Dai, F. Berto
It is very desirable to have good antibacterial properties and mechanical properties at the same time for bone scaffolds. Graphene oxide (GO) can increase the mechanical properties and antibacterial performance, while forsterite (Mg2SiO4) as the matrix can increase forsterite/GO scaffolds’ biological activity for bone tissue engineering. Interconnected porous forsterite scaffolds were developed by space holder processes for bone tissue engineering in this research. The forsterite/GO scaffolds had a porosity of 76%–78% with pore size of 300–450 μm. The mechanism of the mechanical strengthening, antibacterial activity, and cellular function of the forsterite/GO scaffold was evaluated. The findings show that the compressive strength of forsterite/1 wt.% GO scaffold (2.4 ± 0.1 MPa) was significantly increased, in comparison to forsterite scaffolds without GO (1.4 ± 0.1 MPa). Validation of the samples’ bioactivity was attained by forming a hydroxyapatite layer on the forsterite/GO surface within in vitro immersion test. The results of cell viability demonstrated that synthesized forsterite scaffolds with low GO did not show cytotoxicity and enhanced cell proliferation. Antibacterial tests showed that the antibacterial influence of forsterite/GO scaffold was strongly correlated with GO concentration from 0.5 to 2 wt.%. The scaffold encapsulated with 2 wt.% GO had the great antibacterial performance with bacterial inhibition rate around 90%. As results show, the produced forsterite/1 wt.% GO can be an attractive option for bone tissue engineering.
对于骨支架来说,同时具有良好的抗菌性能和力学性能是非常理想的。氧化石墨烯(GO)可以提高机械性能和抗菌性能,而forsterite (Mg2SiO4)作为基质可以提高forsterite/GO支架在骨组织工程中的生物活性。本研究采用空间支架工艺制备了用于骨组织工程的多孔forsterite支架。碳酸盐/氧化石墨烯支架的孔隙率为76% ~ 78%,孔径为300 ~ 450 μm。评估了forsterite/GO支架的机械强化、抗菌活性和细胞功能的机制。结果表明:与未添加氧化石墨烯的forforite支架(1.4±0.1 MPa)相比,forforite /1 wt.% GO支架的抗压强度(2.4±0.1 MPa)显著提高。在体外浸泡试验中,通过在forsterite/GO表面形成羟基磷灰石层来验证样品的生物活性。细胞活力结果表明,低氧化石墨烯合成的forsterite支架没有细胞毒性,细胞增殖能力增强。抑菌试验表明,在0.5 ~ 2 wt.%的氧化石墨烯浓度范围内,福斯特石/氧化石墨烯支架的抑菌效果与氧化石墨烯浓度密切相关。2 wt.%氧化石墨烯包封支架具有良好的抗菌性能,抑菌率在90%左右。结果表明,所制备的forsterite/1 wt.% GO可作为骨组织工程的一种有吸引力的选择。
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引用次数: 3
Three-dimensional culture and chondrogenic differentiation of mesenchymal stem cells in interconnected collagen scaffolds 胶原支架间充质干细胞的三维培养和软骨分化
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-29 DOI: 10.1088/1748-605X/ac61f9
Yan Xie, Linawati Sutrisno, Toru Yoshitomi, N. Kawazoe, Yingnan Yang, Guoping Chen
Interconnected scaffolds are useful for promoting the chondrogenic differentiation of stem cells. Collagen scaffolds with interconnected pore structures were fabricated with poly(lactic acid-co-glycolic acid) (PLGA) sponge templates. The PLGA-templated collagen scaffolds were used to culture human bone marrow-derived mesenchymal stem cells (hMSCs) to investigate their promotive effect on the chondrogenic differentiation of hMSCs. The cells adhered to the scaffolds with a homogeneous distribution and proliferated with culture time. The expression of chondrogenesis-related genes was upregulated, and abundant cartilaginous matrices were detected. After subcutaneous implantation, the PLGA-templated collagen scaffolds further enhanced the production of cartilaginous matrices and the mechanical properties of the implants. The good interconnectivity of the PLGA-templated collagen scaffolds promoted chondrogenic differentiation. In particular, the collagen scaffolds prepared with large pore-bearing PLGA sponge templates showed the highest promotive effect.
相互连接的支架可用于促进干细胞的软骨分化。用聚乳酸-乙醇酸(PLGA)海绵模板制备了具有互连孔结构的胶原支架。利用PLGA模板胶原支架培养人骨髓间充质干细胞(hMSCs),研究其对hMSCs向软骨分化的促进作用。细胞以均匀的分布粘附在支架上,并随着培养时间的推移而增殖。软骨生成相关基因的表达上调,并检测到丰富的软骨基质。皮下植入后,PLGA模板胶原支架进一步增强了软骨基质的产生和植入物的机械性能。PLGA模板胶原支架的良好互连性促进了软骨分化。特别是,用大孔PLGA海绵模板制备的胶原支架显示出最高的促进作用。
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引用次数: 5
Bioinspired TiO2/chitosan/HA coatings on Ti surfaces: biomedical improvement by intermediate hierarchical films 钛表面的仿生TiO2/壳聚糖/透明质酸涂层:中间分层膜的生物医学改善
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-29 DOI: 10.1088/1748-605X/ac61fc
S. Y. Rahnamaee, Shahab Ahmadi Seyedkhani, Aylar Eslami Saed, S. Sadrnezhaad, A. Seza
The most common reasons for hard-tissue implant failure are structural loosening and prosthetic infections. Hence, in this study, to overcome the first problem, different bioinspired coatings, including dual acid-etched, anodic TiO2 nanotubes array, anodic hierarchical titanium oxide (HO), micro- and nanostructured hydroxyapatite (HA) layers, and HA/chitosan (HA/CS) nanocomposite, were applied to the titanium alloy surfaces. X-ray diffraction and FTIR analysis demonstrated that the in situ HA/CS nanocomposite formed successfully. The MTT assay showed that all samples had excellent cell viability, with cell proliferation rates ranging from 120% to 150% after 10 days. The HO coating demonstrated superhydrophilicity (θ ≈ 0°) and increased the wettability of the metallic Ti surface by more than 120%. The friction coefficient of all fabricated surfaces was within the range of natural bone’s mechanical behavior. The intermediate HO layer increased the adhesion strength of the HA/CS coating by more than 60%. The HO layer caused the mechanical stability of HA/CS during the 1000 m of friction test. The microhardness of HA/CS (22.5 HV) and micro-HA (25.5 HV) coatings was comparable to that of human bone. A mechanism for improved adhesion strength of HA/CS coatings by intermediate oxide layer was proposed.
硬组织植入失败的最常见原因是结构松动和假体感染。因此,在本研究中,为了克服第一个问题,将不同的生物启发涂层应用于钛合金表面,包括双酸蚀刻的阳极TiO2纳米管阵列、阳极分级氧化钛(HO)、微结构和纳米结构羟基磷灰石(HA)层以及HA/壳聚糖(HA/CS)纳米复合材料。X射线衍射和FTIR分析表明,原位HA/CS纳米复合材料成功形成。MTT法显示,所有样品都具有良好的细胞活力,10天后细胞增殖率在120%至150%之间。HO涂层表现出超亲水性(θ≈0°),并使金属Ti表面的润湿性提高了120%以上。所有制造表面的摩擦系数都在自然骨骼力学行为的范围内。中间HO层使HA/CS涂层的粘合强度增加了60%以上。HO层在1000m的摩擦试验期间引起HA/CS的机械稳定性。HA/CS(22.5HV)和微HA(25.5HV)涂层的显微硬度与人骨的显微硬度相当。提出了中间氧化层提高HA/CS涂层结合强度的机理。
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引用次数: 8
Strontium-loaded titanium implant with rough surface modulates osseointegration by changing sfrp4 in canonical and noncanonical Wnt signaling pathways 表面粗糙的锶负载钛植入物通过改变经典和非经典Wnt信号通路中的sfrp4来调节骨整合
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-29 DOI: 10.1088/1748-605X/ac61fb
Xiaoyi Wang, He Xin, Xiaona Ning, Yubohan Zhang, Fuwei Liu, Zhouyang Zhang, Xuelian Jia, Weiwei Guo, Y. Hong, Wenquan Sui
A rough morphology and strontium (Sr) can activate the Wnt pathway to regulate bone mesenchymal stem cells (rBMSCs) osteogenic differentiation, but the mechanism remains unclear. We constructed smooth Ti (ST) surfaces, rough Ti (RT) surfaces subjected to hydrofluoric acid etching, strontium-loaded smooth Ti (ST-Sr) surfaces subjected to magnetron sputtering, and rough strontium-loaded Ti (RT-Sr) surfaces. We systematically studied the in vitro osteogenic differentiation of rBMSCs on these four surfaces by alkaline phosphatase measurement, Alizarin Red staining and polymerase chain reaction (PCR). We also investigated whether crosstalk of the canonical and noncanonical Wnt signaling pathways regulated by sfrp4, which is an inhibitor of canonical and noncanonical Wnt, is the underlying mechanism via PCR on rBMSCs in different stages of osteogenic differentiation. We confirmed the effect of sfrp4 through an in vivo sfrp4-siRNA test. The in vitro osteogenic differentiation of rBMSCs decreased in the order RT-Sr, RT, ST-Sr, and ST. Regarding the mechanism, rough morphology and Sr both enhanced the canonical Wnt pathway to promote osseointegration. Additionally, rough morphology can inhibit sfrp4 to activate the noncanonical Wnt pathway, and then, the activated noncanonical Wnt pathway can suppress the canonical Wnt pathway at the early stage of osteogenic differentiation. Sr continuously enhanced sfrp4 to inhibit the canonical Wnt pathway instead of activating the noncanonical Wnt pathway. Interestingly, the effect of rough morphology on sfrp4 changed from inhibition to enhancement, and the enhancing effect of Sr on sfrp4 was gradually attenuated. The results of the in vivo sfrp4-siRNA test showed that osseointegration decreased in the order RT-Sr, RT-Sr-siRNA, and ST. Our results suggest that the lack of sfrp4 could suppress osseointegration, indicating that sfrp4 acts as a crucial regulatory molecule for the canonical and noncanonical Wnt pathways during the response of rBMSCs to rough morphology and Sr.
粗糙的形态和锶(Sr)可以激活Wnt通路来调节骨髓间充质干细胞(rBMSCs)的成骨分化,但其机制尚不清楚。我们构建了光滑的Ti(ST)表面、经过氢氟酸蚀刻的粗糙的Ti(RT)表面、经磁控溅射的载有锶的光滑Ti(ST-Sr)表面和经过锶的粗糙Ti(RT-Str)表面。我们通过碱性磷酸酶测定、茜素红染色和聚合酶链式反应(PCR)系统地研究了rBMSCs在这四个表面上的体外成骨分化。我们还研究了由sfrp4调节的经典和非经典Wnt信号通路的串扰是否是在成骨分化的不同阶段通过PCR对rBMSCs的潜在机制。我们通过体内sfrp4-siRNA测试证实了sfrp4的作用。rBMSCs的体外成骨分化按RT-Sr、RT、ST-Sr和ST的顺序降低。在机制方面,粗糙形态和Sr都增强了促进骨整合的经典Wnt途径。此外,粗糙形态学可以抑制sfrp4激活非经典Wnt通路,然后,在成骨分化的早期阶段,激活的非经典Wnt通路可以抑制经典Wnt途径。Sr持续增强sfrp4以抑制经典Wnt途径,而不是激活非经典Wnt通路。有趣的是,粗糙形态对sfrp4的作用从抑制变为增强,Sr对sfrp4的增强作用逐渐减弱。体内sfrp4-siRNA测试结果显示,骨整合按RT-Sr、RT-Sr-siRNA和ST的顺序减少。我们的结果表明,缺乏sfrp4可以抑制骨整合,表明在rBMSCs对粗糙形态和Sr的反应过程中,sfrp4是经典和非经典Wnt途径的关键调节分子。
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引用次数: 1
Unravelling the effects of ibuprofen-acetaminophen infused copper-bioglass towards the creation of root canal sealant 揭示布洛芬-对乙酰氨基酚注入铜生物玻璃对根管密封剂产生的影响
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-08 DOI: 10.1088/1748-605X/ac5b83
C. S, Riju Chandran, Ramya R, D. D., B. S
Impact towards the tuneable characteristics of bioactive glasses (BAGs) has been explored; as there is no root canal sealant till date with ideal characteristics competent enough to manoeuvre the perplexing root canal architecture. Combeite, calcite and traces of cuprorivaite crystalline phases were validated for material formation, in which Cu 2P (XPS) peak authenticating the presence of copper in bioglass network (Cu-BAG). Spherical and platelet-like morphologies were observed and the grain size of Cu-BAG (∼100 nm) was lesser as compared to BAG (∼1 µm). These particle distributions impacted the porosity, and dominant non-bridging oxygens in Cu-BAG influences ionic dissolution, which subsequently enhanced the mineralization. These bioactive materials were loaded with acetaminophen and ibuprofen, corresponding organic moieties was confirmed through Fourier transform infra-red. These drugs loaded bioactive materials exhibited tremendous anti-inflammatory and anti-microbial behaviour with better sealing ability. Drug loaded bioglass paste filled in biomechanically prepared root canal was estimated for sealing potential, mineralization, micro leakage, and fracture resistance properties. Hydroxyl apatite growth was noted on the sealants, flower like protuberance confirmed the sealing potential of the prepared material. Bioglass exhibited promising characteristics required in a root canal sealant. This investigation is a step further towards tailoring the properties of bioactive materials as promising candidates in root canal obturation and thereof.
已经探索了对生物活性玻璃(BAG)的可调谐特性的影响;因为到目前为止,还没有具有理想特性的根管封闭剂能够操纵令人困惑的根管结构。对于材料的形成,验证了Combeite、方解石和痕量铜晶相,其中Cu2P(XPS)峰证实了生物玻璃网络(Cu-BAG)中存在铜。观察到球形和片状形态,与BAG(~1µm)相比,Cu BAG的晶粒尺寸(~100 nm)较小。这些颗粒分布影响了孔隙率,并且Cu BAG中的主要非桥接氧影响离子溶解,从而增强了矿化。这些生物活性材料负载了对乙酰氨基酚和布洛芬,通过傅立叶变换红外光谱确认了相应的有机部分。这些药物负载的生物活性材料表现出巨大的抗炎和抗微生物行为,具有更好的密封能力。在生物力学制备的根管中填充载药生物玻璃糊剂,评估其封闭潜力、矿化、微渗漏和抗断裂性能。在密封剂上观察到羟基磷灰石的生长,花状突起证实了所制备材料的密封潜力。生物玻璃显示出根管封闭剂所需的良好特性。这项研究是进一步调整生物活性材料的特性,使其成为根管充填及其应用的有前途的候选者。
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引用次数: 3
A review: potential application and outlook of photothermal therapy in oral cancer treatment 综述了光热疗法在口腔癌治疗中的潜在应用及展望
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-03-02 DOI: 10.1088/1748-605X/ac5a23
Liren Cao, Yongzhi Wu, Yue Shan, Bowen Tan, Jinfeng Liao
As one of the most common malignant tumors, oral cancer threatens people’s health worldwide. However, traditional therapies, including surgery, radiotherapy, and chemotherapy cannot meet the requirement of cancer cure. Photothermal therapy (PTT) has attracted widespread attentions for its advantages of the noninvasive process, few side effects, and promising tumor ablation. Up to now, three types of photothermal agents (PTAs) have been widely employed in oral cancer therapies, which involve metallic materials, carbon-based materials, and organic materials. Previous research mainly introduced hybrid materials due to benefits from the synergistic effect of multiple functions. In this review, we present the advancement of each type PTAs for oral cancer treatment in recent years. In each part, we introduce the properties and synthesis of each PTA, summarize the current studies, and analyze their potential applications. Furthermore, we discuss the status quo and the deficiencies hindering the clinical application of PTT, based on which gives the perspective of its future developing directions.
口腔癌作为最常见的恶性肿瘤之一,威胁着全世界人民的健康。然而,传统的治疗方法,包括手术、放疗和化疗,不能满足癌症治愈的要求。光热疗法(PTT)因其无创、副作用小、治疗肿瘤有前景等优点而受到广泛关注。目前在口腔癌治疗中广泛应用的光热剂有金属材料、碳基材料和有机材料三种。由于多种功能的协同效应,以往的研究主要是引入杂化材料。本文就近年来各类pta在口腔癌治疗中的应用进展作一综述。在每个部分,我们介绍了各种PTA的性质和合成方法,总结了目前的研究现状,并分析了它们的应用前景。在此基础上,讨论了PTT临床应用的现状及存在的不足,并对其未来的发展方向进行了展望。
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引用次数: 6
In vitro and in vivo study of magnesium containing bioactive glass nanoparticles modified gelatin scaffolds for bone repair 含镁生物活性玻璃纳米粒子修饰明胶骨修复支架的体内外研究
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-02-28 DOI: 10.1088/1748-605X/ac5949
Yi Sun, Jie Lin, Leilei Li, K. Jia, Wen Xia, Chao Deng
Magnesium containing bioactive glass nanoparticles modified gelatin scaffolds (MBGNs/Gel scaffolds) have shown recently the potential for bone regeneration due to its good biocompatibility, bioresorbability and bioactivity. Nevertheless, its use is limited by its complicated manufacturing process and a relatively expensive price. In this study, MBGNs were prepared by sol–gel process. The MBGNs/Gel was synthesized by a simple immersion method. SEM, transmission electron microscopy and dynamic light scattering analysis showed that the particles had spherical morphology with mean particle size of 100 nm. The MBGNs/Gel scaffolds were observed by SEM. The scaffolds showed connected pore structure with pore size ranging from 100 to 300 μm. SEM images with high magnification showed the existence of MBGNs on the surface of micro-pores. The ion release results revealed the release of Mg, Ca and Si elements from the MBGNs. MTT assay and cytotoxicity studies indicated that, the scaffolds provide a suitable ion related micro-environment for cell attachment and spreading. The Reverse Transcription-Polymerase Chain Reaction (RT-PCR) results showed the scaffolds could promote the osteogenesis of MC3T3-E1. The in vivo study also showed higher amount of new bone and trabecular bone which indicated excellent bone induction and conduction property of modified scaffolds. So, the developed MBGNs/Gel scaffolds are a potential candidate for bone regeneration applications.
含镁生物活性玻璃纳米颗粒改性明胶支架(MBGNs/Gel支架)由于其良好的生物相容性、生物可吸收性和生物活性,近年来显示出骨再生的潜力。然而,它的使用受到其复杂的制造工艺和相对昂贵的价格的限制。本研究采用溶胶-凝胶法制备MBGNs。采用简单的浸渍法合成了MBGNs/Gel。SEM、透射电子显微镜和动态光散射分析表明,颗粒呈球形,平均粒径为100nm。用扫描电镜观察了MBGNs/Gel支架的结构,结果表明,MBGNs/Gel支架具有连通的孔结构,孔径在100~300μm之间。高放大率的SEM图像显示微孔表面存在MBGNs。离子释放结果揭示了Mg、Ca和Si元素从MBGNs中的释放。MTT法和细胞毒性研究表明,该支架为细胞的附着和扩散提供了合适的离子相关微环境。逆转录聚合酶链反应(RT-PCR)结果表明,支架能促进MC3T3-E1的成骨。体内研究还显示了更高数量的新骨和小梁骨,这表明改性支架具有良好的骨诱导和传导性能。因此,所开发的MBGNs/Gel支架是骨再生应用的潜在候选者。
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引用次数: 1
Promoting in-vivo bone regeneration using facile engineered load-bearing 3D bioactive scaffold 利用简易工程负重3D生物活性支架促进体内骨再生
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-02-25 DOI: 10.1088/1748-605X/ac58d6
Saumya Dash, Pinky, Varun Arora, Kunj Sachdeva, Harshita Sharma, A. Dinda, A. Agrawal, M. Jassal, S. Mohanty
The worldwide incidence of bone disorders has trended steeply upward and is expected to get doubled by 2030. The biological mechanism of bone repair involves both osteoconductivity and osteoinductivity. Despite the self-healing functionality after injury, bone tissue faces a multitude of pathological challenges. Several innovative approaches have been developed to prepare biomaterial-based bone grafts. To design a suitable bone material, the freeze-drying technique has achieved significant importance among the other conventional methods. However, the functionality of the polymeric freeze-dried scaffold in in-vivo osteogenesis is in a nascent stage. In this study facile, freeze-dried, biomaterial-based load-bearing three-dimensional porous composite scaffolds have been prepared. The biocompatible scaffolds have been made by using chitosan (C), polycaprolactone (P), hydroxyapatite (H), glass ionomer (G), and graphene (gr). Scaffolds of eight different groups (C, P, CP, CPH, CPHG, CPHGgr1, CPHGgr2, CPHGgr3) have been designed and characterized to evaluate their applicability in orthopedics. To evaluate the efficacy of the scaffolds a series of physio-chemical, morphological, and in-vitro and in-vivo biological experiments have been performed. From the obtained results it was observed that the CPHGgr1 is the ideal compatible material for Wharton’s jelly-derived mesenchymal stem cells (MSCs) and the blood cells. The in-vitro bone-specific gene expression study revealed that the scaffold assists MSCs osteogenic differentiation. Additionally, the in-vivo study on the mice model was also performed for a period of four and eight weeks. The subcutaneous implantation of the designed scaffolds did not show any altered physiological condition in the animals, which indicated the in-vivo biocompatibility of the designed material. The histopathological study revealed that after eight weeks of implantation, the CPHGgr1 scaffold supported significantly better collagen deposition and calcification. The facile designing of the CPHGgr1 multicomponent nanocomposite provided an osteo-regenerative biomaterial with desired mechanical strength as an ideal regenerative material for cancellous bone tissue regeneration.
全球骨疾病发病率呈急剧上升趋势,预计到2030年将翻一番。骨修复的生物学机制包括骨传导和骨诱导。尽管骨组织在损伤后具有自愈功能,但骨组织面临着许多病理挑战。已经开发了几种创新的方法来制备基于生物材料的骨移植物。为了设计合适的骨材料,冷冻干燥技术在其他常规方法中具有重要意义。然而,聚合物冻干支架在体内成骨中的功能尚处于初级阶段。在这项研究中,制备了易于使用的、冷冻干燥的、基于生物材料的三维多孔复合材料承重支架。采用壳聚糖(C)、聚己内酯(P)、羟基磷灰石(H)、玻璃离聚体(G)和石墨烯(gr)制备了生物相容性支架。设计并表征了8种不同类型的支架(C、P、CP、CPH、CPHG、CPHGgr1、CPHGgr2、CPHGgr3),以评价其在骨科中的适用性。为了评估支架的功效,我们进行了一系列的理化、形态学、体外和体内生物学实验。结果表明,CPHGgr1是沃顿氏凝胶源间充质干细胞(MSCs)和血细胞的理想相容性材料。体外骨特异性基因表达研究表明,该支架有助于MSCs成骨分化。此外,还对小鼠模型进行了为期4周和8周的体内研究。所设计的支架皮下植入后,动物的生理状况未发生任何改变,表明所设计材料具有良好的体内生物相容性。组织病理学研究显示,植入8周后,CPHGgr1支架支持的胶原沉积和钙化明显改善。CPHGgr1多组分纳米复合材料的简单设计提供了一种具有理想机械强度的骨再生生物材料,是一种理想的松质骨组织再生材料。
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引用次数: 2
Aptamer-functionalized targeted siRNA delivery system for tumor immunotherapy. 用于肿瘤免疫治疗的适体功能化靶向siRNA递送系统。
IF 4 3区 医学 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2022-02-09 DOI: 10.1088/1748-605X/ac5382
Haiyin Lv, Tengfei Wang, F. Ma, Kunchi Zhang, Tian Gao, R. Pei, Ye Zhang
Programmed death ligand 1 (PD-L1) overexpressed on the surface of tumor cells is one of the reasons for tumor immune escape. Reducing PD-L1 expression has been proved to be an effective strategy to facilitate immune system activation and inhibit tumor progression. RNA interference (RNAi) is a promising technology for gene regulation in tumor therapy. In this study, we constructed a targeted siRNA delivery system NPs@apt to transfect PD-L1 siRNA into human non-small-cell lung carcinoma cell line (A549) for inhibiting tumor immune evasion. NPs@apt was prepared by compressing PD-L1 siRNA with cationic Lipofectamine 2000, fusing with erythrocyte membrane-derived nanovesicles, and further modifying with targeting AS1411 aptamer. The introduction of erythrocyte membrane endows the siRNA delivery system with lower cytotoxicity and the ability to escape from the phagocytosis of macrophages. The stability of NPs@apt and the protection to loaded siRNA were confirmed. In vitro studies after NPs@apt treatment demonstrated that PD-L1 siRNA was selectively delivered into A549 cells, and further resulted in PD-L1 gene knockdown, T cell activation and tumor cell growth inhibition. This study offers an alternative strategy for specific siRNA transfection for improving anti-tumor immunity.
程序性死亡配体1 (Programmed death ligand 1, PD-L1)在肿瘤细胞表面过表达是肿瘤免疫逃逸的原因之一。降低PD-L1的表达已被证明是促进免疫系统激活和抑制肿瘤进展的有效策略。RNA干扰(RNAi)是一种很有前途的肿瘤基因调控技术。本研究构建靶向siRNA传递系统NPs@apt,将PD-L1 siRNA转染人非小细胞肺癌细胞系(A549),抑制肿瘤免疫逃逸。用阳离子Lipofectamine 2000压缩PD-L1 siRNA,与红细胞膜源性纳米囊泡融合,并进一步靶向AS1411适配体修饰,制备NPs@apt。红细胞膜的引入使siRNA传递系统具有较低的细胞毒性和逃避巨噬细胞吞噬的能力。证实了NPs@apt的稳定性和对负载siRNA的保护作用。NPs@apt处理后的体外研究表明,PD-L1 siRNA被选择性地递送到A549细胞中,并进一步导致PD-L1基因敲低、T细胞活化和肿瘤细胞生长抑制。本研究为特异性siRNA转染提高抗肿瘤免疫提供了一种替代策略。
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引用次数: 4
期刊
Biomedical materials
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