• 【在藻酸盐水凝胶中培养的间充质基质细胞成骨分化过程中的超微结构变化。】 复制标题 收藏 收藏
    DOI:10.1186/s13578-016-0128-0 复制DOI
    作者列表:Grzesiak J,Śmieszek A,Marycz K
    BACKGROUND & AIMS: BACKGROUND:Osteogenic differentiation of mesenchymal stem cells has been extensively investigated with regards to different aspects, including the analysis of cell intracellular and extracellular proteome, cell gene expression pattern, and morphology. During the osteogenic differentiation, osteoblasts produce and release specific proteins, like osteocalcin and osteopontin. Simultaneously, cells produce the extracellular matrix (ECM) that resembles the bone ECM, with high quantity of calcium and phosphorus. We focused on the ultrastructural changes occurring during the osteogenic differentiation of MSC cultured in alginate hydrogel. RESULTS:The analysis revealed that during the osteogenic differentiation the most of cells become dead, and these dead cells contain large quantities of calcium and deposition is strictly connected with the cellular death and small membrane vesicles released by cells. Cell organelles were not present within differentiated cells, while in cells from non-osteogenic group the cellular ultrastructure was proper, with single nuclei, endoplasmic reticulum and numerous mitochondria. CONCLUSION:The ECM synthesis and deposition during the osteogenic differentiation of MSC involves cellular programmed death. The small membrane vesicles become the mineralization sites of formed bone ECM.
    背景与目标:
  • 【生物相容性水凝胶前体与磷灰质磷酸钙水泥 (CPC) 的结合: 原位水凝胶网状对CPC性能的影响。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.b.34685 复制DOI
    作者列表:Ramirez Caballero SS,Ferri-Angulo D,Debret R,Granier F,Marie S,Lefèvre FX,Bouler JM,Despas C,Sohier J,Bujoli B
    BACKGROUND & AIMS: :In the field of bone regenerative medicine, injectable calcium phosphate cements (CPCs) are used for decades in clinics, as bone void fillers. Most often preformed polymers (e.g., hyaluronic acid, collagen, chitosan, cellulose ethers…) are introduced in the CPC formulation to make it injectable and improve its cohesion. Once the cement has hardened, the polymer is simply trapped in the CPC structure and no organic subnetwork is present. By contrast, in this work a CPC was combined with organic monomers that reticulated in situ so that a continuous biocompatible 3D polymeric subnetwork was formed in the CPC microstructure, resulting in a higher permeability of the CPC, which might allow to accelerate its in vivo degradation. Two options were investigated depending on whether the polymer was formed before the apatitic inorganic network or concomitantly. In the former case, conditions were found to reach a suitable rheology for easy injection of the composite. In addition, the in situ formed polymer was shown to strongly affect the size, density, and arrangement of the apatite crystals formed during the setting reaction, thereby offering an original route to modulate the microstructure and porosity of apatitic cements.
    背景与目标: : 在骨再生医学领域,可注射的磷酸钙水泥 (cpc) 在临床上使用了数十年,作为骨空隙填充剂。在CPC配方中引入最常见的预制聚合物 (例如,透明质酸,胶原蛋白,壳聚糖,纤维素醚……),以使其可注射并改善其凝聚力。水泥硬化后,聚合物仅被困在CPC结构中,不存在有机子网。相比之下,在这项工作中,CPC与原位网状的有机单体结合,从而在CPC微结构中形成了连续的生物相容性3D聚合物子网络,从而导致CPC的渗透性更高,这可能会加速其体内降解。根据聚合物是在磷灰质无机网络之前形成还是同时形成,研究了两种选择。在前一种情况下,发现条件达到了易于注入复合材料的合适流变学。此外,原位形成的聚合物显示出强烈影响凝固反应过程中形成的磷灰石晶体的尺寸,密度和排列,从而提供了调节磷灰石水泥的微观结构和孔隙率的原始途径。
  • 【辐射合成用于芦丁控释的聚 (淀粉/丙烯酸) pH敏感水凝胶。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijbiomac.2016.07.079 复制DOI
    作者列表:Abdel Ghaffar AM,Radwan RR,Ali HE
    BACKGROUND & AIMS: :The copolymerization of starch with acrylic acid AAc using direct gamma radiation technique was performed. The effect of AAc concentrations on the gel (%) and swelling behavior were investigated. It is found that as AAc concentrations increase both gel(%) and swelling behavior increase. The Poly(starch/acrylic acid) (1:10wt%) hydrogel were selected due to its high swelling properties. From the in-vitro release study of the rutin-loaded hydrogel it is observed that it is strong pH-dependent release behavior, thus offering a maximum release as pH increased. The dextran sulphate sodium (DSS)-induced rat colitis model was treated with rutin-loaded Poly(starch/acrylic acid) (1:10wt%) hydrogel and free rutin solution by oral administration. Colitic control group showed a significant elevation in colon/body weight ratio, myeloperoxgidase activity, tumor necrosis factor, nitric oxide and malondialdehyde levels. However, glutathione level was reduced. It was found that the rutin-loaded hydrogel was more efficient than free rutin as evidenced by improvement of all measured parameters. These effects were confirmed histopathologically and may be attributed to its ability to control delivery of rutin to colon with minor early release of rutin before colon. The Poly(starch/acrylic acid) (1:10wt%) can represent a pivotal anti-inflammatory approach for patients with inflammatory bowel disease in order to increase efficacy and reduce toxicity.
    背景与目标: : 使用直接伽马辐射技术进行了淀粉与丙烯酸AAc的共聚。研究了AAc浓度对凝胶 (%) 和溶胀行为的影响。发现随着AAc浓度的增加,凝胶 (%) 和溶胀行为均增加。选择聚 (淀粉/丙烯酸) (1:10wt %) 水凝胶,因为它具有高溶胀性能。从负载芦丁的水凝胶的体外释放研究中可以看出,它具有很强的pH依赖性释放行为,因此随着pH的增加而提供最大的释放。用芦丁负载的聚 (淀粉/丙烯酸) (1:10wt %) 水凝胶和游离芦丁溶液口服处理葡聚糖硫酸钠 (DSS) 诱导的大鼠结肠炎模型。结肠对照组的结肠/体重比,髓过氧化物酶活性,肿瘤坏死因子,一氧化氮和丙二醛水平显着升高。然而,谷胱甘肽水平降低。已发现,装载芦丁的水凝胶比游离芦丁更有效,这可以通过改善所有测量参数来证明。这些作用已在组织病理学上得到证实,可能归因于其控制芦丁向结肠的递送的能力,而在结肠前少量早期释放芦丁。聚 (淀粉/丙烯酸) (1:10wt %) 可以代表炎症性肠病患者的关键抗炎方法,以提高疗效并降低毒性。
  • 【光电流体印刷系统,用于制造具有按需图案化细胞和微粒的水凝胶片。】 复制标题 收藏 收藏
    DOI:10.1088/1758-5090/aa564c 复制DOI
    作者列表:Gi HJ,Han D,Park JK
    BACKGROUND & AIMS: :This paper presents a novel optoelectrofluidic printing system that facilitates not only the optoelectrofluidic patterning of microparticles and mammalian cells but also the harvesting of the patterned microparticles encapsulated within poly(ethylene glycol) dicarylate (PEGDA) hydrogel sheets. Although optoelectrofluidic technology has numerous advantages for programmable and on-demand patterning and the feasibility of manipulating single microparticles, practical applications using existing laboratory infrastructure in biological and clinical research fields have been strictly restricted due to the impossibility of recovering the final patterned product. In order to address these harvesting limitations, PEGDA was employed to utilize optoelectrofluidic printing. The Clausius-Mossotti factor was calculated to investigate the dielectrophoretic mobility of the microparticle and the cell in the PEGDA precursor solution. As a proof of concept, three basic controllabilities of the optoelectrofluidic printing system were characterized: the number of microparticles, the distance between the microparticle columns, and the ratio of two different microparticles. Furthermore, the optoelectrofluidic patterning and printing of human liver carcinoma cells (HepG2) were demonstrated in 5 min with a single-cell level of resolution. The appropriate ranges of frequency were experimentally defined based on the calculated result of the dielectrophoretic mobility of HepG2 cells. Finally, optoelectrofluidically cell-patterned hydrogel sheets were successfully recovered under a highly viable physiological condition.
    背景与目标: : 本文介绍了一种新颖的光电流体打印系统,该系统不仅有助于微粒和哺乳动物细胞的光电流体图案化,而且还可以收集封装在聚 (乙二醇) 二芳酸酯 (PEGDA) 水凝胶片中的图案化微粒。尽管光电流体技术在可编程和按需图案化以及操纵单个微粒的可行性方面具有许多优势,但由于不可能回收最终图案化产品,因此在生物和临床研究领域中使用现有实验室基础设施的实际应用受到严格限制。为了解决这些收获限制,使用了PEGDA来利用光电流体打印。计算了Clausius-Mossotti因子,以研究PEGDA前体溶液中微粒和细胞的介电电泳迁移率。作为概念证明,对光电流体打印系统的三个基本控制性进行了表征: 微粒的数量,微粒柱之间的距离以及两种不同微粒的比例。此外,在5分钟内以单细胞水平的分辨率证明了人肝癌细胞 (HepG2) 的光电流体图案化和印刷。根据HepG2细胞的介电电泳迁移率的计算结果,实验确定了适当的频率范围。最后,在高度可行的生理条件下,成功地回收了光电流体细胞图案化的水凝胶片。
  • 【不同参数对药物从水凝胶系统释放到生物膜模型的影响。差示扫描量热法评价。】 复制标题 收藏 收藏
    DOI:10.1016/s0142-9612(99)00252-5 复制DOI
    作者列表:Castelli F,Pitarresi G,Giammona G
    BACKGROUND & AIMS: :A comparative study on the drug release capacity of four water swellable polymeric systems was carried out by differential scanning calorimetry (DSC). The polymeric systems chosen were alpha,beta-polyaspartahydrazide (PAHy) crosslinked by glutaraldehyde (GLU) (PAHy-GLU) or by ethyleneglycoldiglycidylether (EGDGE), (PAHy-EGDGE), polyvinylalcohol (PVA) crosslinked by glutaraldehyde (PVA-GLU) and alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) by gamma irradiation (PHEA-gamma matrices). The degree of crosslinking for PAHy-GLU, PAHy-EGDGE and PVA-GLU samples was about 0.4 and 0.8. These hydrogels were characterized as free of drugs and were loaded with diflunisal (DFN) (approximately 2.5% w/w). Diflunisal, a non-steroidal anti-inflammatory drug, has been chosen as a model drug to be incorporated into polymeric matrices to follow the release processes of a drug from these hydrogels to a model membrane made by unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). Differential scanning calorimetry appears to be a suitable technique to follow the transfer kinetics of the drug from the controlled release system to the biomembrane model. The drug releases from all the considered polymeric hydrogels, were compared with the release observed from the drug solid form by examining the effects on the thermotropic behaviour of DPPC unilamellar vesicles. The release kinetics of the drug from hydrogels were followed at 25, 37 and 50 degrees C to evidence the influence of temperature on the drug release and on the successive transfer to biological membrane model. Particularly, it appears evident that the total amount of drug transferred and the release rate are affected by the polymer crosslinking degree (it increases with crosslinking decrease) as well as by the nature of crosslinking agent. In fact, the drug release profiles from PAHy-GLU samples are more differentiated than those from PAHy-EGDGE. The effect of parameters correlating with the properties of starting polymer, such as water-affinity, crystallinity, glass-to-rubber transition temperature and affinity towards drug molecules, has been also evaluated.
    背景与目标: : 通过差示扫描量热法 (DSC) 对四种水可溶胀聚合物体系的药物释放能力进行了比较研究。选择的聚合物体系是由戊二醛 (GLU) (PAHy-GLU) 或由乙二醇二缩水甘油醚 (EGDGE),(PAHy-EGDGE) 交联的 α,β-聚天冬酰肼 (PAHy),聚乙烯醇 (PVA) 交联的戊二醛 (PVA-GLU) 和 α,Γ 辐照的 β-聚 (N-羟乙基)-DL-天冬酰胺 (PHEA) (PHEA-γ 基质)。PAHy-GLU、PAHy-EGDGE和pva-glu样品的交联度为约0.4和0.8。这些水凝胶被表征为不含药物并且负载有二氟尼铝 (DFN) (约2.5% w/w)。已选择非甾体类抗炎药Diflunisal作为模型药物,将其掺入聚合物基质中,以遵循药物从这些水凝胶释放到由二棕榈酰磷脂酰胆碱 (DPPC) 的单层囊泡制成的模型膜的过程。差示扫描量热法似乎是跟踪药物从控释系统到生物膜模型的转移动力学的合适技术。通过检查对DPPC单层囊泡的热致行为的影响,将所有考虑的聚合物水凝胶的药物释放与药物固体形式的释放进行了比较。在25、37和50 ℃ 下跟踪药物从水凝胶的释放动力学,以证明温度对药物释放和连续转移到生物膜模型的影响。特别地,显而易见的是,转移的药物总量和释放速率受聚合物交联度 (其随着交联度的降低而增加) 以及交联剂的性质的影响。实际上,PAHy-GLU样品的药物释放特征比PAHy-EGDGE样品的药物释放特征更加不同。还评估了与起始聚合物性能相关的参数的影响,例如水亲和力,结晶度,玻璃到橡胶的转变温度以及对药物分子的亲和力。
  • 【沉积速率和镜片护理对galyfilcon A有机硅水凝胶镜片的影响。】 复制标题 收藏 收藏
    DOI:10.1097/01.opx.0000236804.13317.65 复制DOI
    作者列表:Nichols JJ
    BACKGROUND & AIMS: PURPOSE:The purpose of this study is to investigate the frequency of deposition and impact of various multipurpose care regimens on a silicone hydrogel contact lens material (galyfilcon A; Acuvue Advance, Vistakon, Inc.). METHODS:This was a two-phase, monadic, open-label, daily-wear clinical study. The analyses from Phase I were aimed at determining total lens front surface area deposition after two 2-week periods of galyfilcon A lens wear. Deposition was graded clinically using a slit-lamp biomicroscope from grade 0 (0% surface area) to grade 4 (>25% surface area). Secondary outcomes included visual acuity and self-reported overall comfort, end-of-day comfort, and perceived vision. Phase II determined the impact of various multipurpose solutions with and without a rub step on "heavy depositors" (grade 3 or 4) from a single phase I site. There were four arms associated with phase II, and front surface deposition was again the primary outcome with the same secondary outcomes as that mentioned previously. RESULTS:In phase I, after the initial 2-week wear period, 9.4% of subjects exhibited grades 3 and 4 deposition. There were no differences in visual acuity, comfort, end-of-day comfort, and self-reported perceived vision when comparing "depositors" and "nondepositors." Twenty-seven "heavy depositors" from phase I completed phase II. After using Complete MoisturePlus (with a digital rub), no patients (0%) had clinically significant (grades 3 or 4) deposition, whereas for comparison, 33% of patients (the "heavy depositors") from phase I had clinically significant deposition without a digital rub (p=0.003). Similarly, 3.7% of patients had grade 3 or 4 deposition after using Opti-Free Express (with a digital rub) (p=0.01) and AOSEPT with a Miraflow-based rub (p=0.01) compared with the 33% of patients using Complete MoisturePlus without a digital rub. There were no differences in visual acuity or self-reported outcomes when stratified by lens care system in phase II. CONCLUSIONS:Less than 10% of subjects exhibit clinically significant levels of deposition with galyfilcon A lenses when cleaned with Complete MoisturePlus (no-rub) multipurpose solution, and this was shown to not interfere with lens performance. The addition of a rub-and-rinse step to the care of galyfilcon lenses significantly reduces this deposition rate.
    背景与目标:
  • 【一种基于胆囊细胞外基质的骨骼肌组织工程混合水凝胶。】 复制标题 收藏 收藏
    DOI:10.1002/jbm.a.36955 复制DOI
    作者列表:Raj R,Sobhan PK,Pratheesh KV,Anilkumar TV
    BACKGROUND & AIMS: :Tailoring the properties of extracellular matrix (ECM) based hydrogels by conjugating with synthetic polymers is an emerging method for designing hybridhydrogels for a wide range of tissue engineering applications. In this study, poly(ethylene glycol) diacrylate (PEGDA), a synthetic polymer at variable concentrations (ranging from 0.2 to 2% wt/vol) was conjugated with porcine cholecyst derived ECM (C-ECM) (1% wt/vol) and prepared a biosynthetic hydrogel having enhanced physico-mechanical properties, as required for skeletal muscle tissue engineering. The C-ECM was functionalized with acrylate groups using activated N-hydroxysuccinimide ester-based chemistry and then conjugated with PEGDA via free-radical polymerization in presence of ammonium persulfate and ascorbic acid. The physicochemical characteristics of the hydrogels were evaluated by Fourier transform infrared spectroscopy and environmental scanning electron microscopy. Further, the hydrogel properties were studied by evaluating rheology, swelling, gelation time, percentage gel fraction, in vitro degradation, and mechanical strength. Biocompatibility of the gel formulations were assessed using the C2C12 skeletal myoblast cells. The hydrogel formulations containing 0.2 and 0.5% wt/vol of PEGDA were non-cytotoxic and found suitable for growth and proliferation of skeletal myoblasts. The study demonstrated a method for modulating the properties of ECM hydrogels through conjugation with bio-inert polymers for skeletal muscle tissue engineering applications.
    背景与目标: : 通过与合成聚合物缀合来定制基于细胞外基质 (ECM) 的水凝胶的特性是设计用于广泛组织工程应用的杂化水凝胶的新兴方法。在这项研究中,聚 (乙二醇) 二丙烯酸酯 (PEGDA) 是一种不同浓度 (范围为0.2至2% wt/vol) 的合成聚合物,与猪胆囊素衍生的ECM (c-ecm) (1% wt/vol) 缀合,并制备了具有增强的物理机械性能的生物合成水凝胶。根据骨骼肌组织工程的要求。使用活化的N-羟基琥珀酰亚胺酯基化学将c-ecm用丙烯酸酯基团官能化,然后在过硫酸铵和抗坏血酸存在下通过自由基聚合与PEGDA共轭。通过傅立叶变换红外光谱和环境扫描电子显微镜评估了水凝胶的理化特性。此外,通过评估流变学,溶胀,凝胶时间,凝胶分数百分比,体外降解和机械强度来研究水凝胶性能。使用C2C12骨骼肌成肌细胞评估凝胶制剂的生物相容性。含有0.2和0.5% 重量/体积的PEGDA的水凝胶制剂是非细胞毒性的,并且发现适合骨骼肌成肌细胞的生长和增殖。该研究证明了一种通过与生物惰性聚合物缀合来调节ECM水凝胶性能的方法,用于骨骼肌组织工程应用。
  • 【工程合成水凝胶微环境以指导干细胞。】 复制标题 收藏 收藏
    DOI:10.1016/j.copbio.2013.03.009 复制DOI
    作者列表:Guvendiren M,Burdick JA
    BACKGROUND & AIMS: :Advances in our understanding and ability to manipulate stem cell behavior are helping to move stem cell-based therapies toward the clinic. However, much of our knowledge has been gained from standard 2-dimensional culture systems, which often misrepresent many of the signals that stem cells receive in their native 3-dimensional environments. Fortunately, the field of synthetic hydrogels is developing to better recapitulate many of these signals to guide stem cell behavior, both as in vitro models and as delivery vehicles for in vivo implantation. These include a multitude of structural and biochemical cues that can be presented on the cellular scale, such as degradation, adhesion, mechanical signals, topography, and the presentation of growth factors, often with precise spatiotemporal control.
    背景与目标: : 我们对干细胞行为的理解和操纵能力的进步正在帮助将基于干细胞的疗法推向临床。然而,我们的大部分知识是从标准的2维培养系统中获得的,该系统经常歪曲干细胞在其天然3维环境中接收的许多信号。幸运的是,合成水凝胶的领域正在发展,以更好地概括许多这些信号,以指导干细胞行为,无论是作为体外模型还是作为体内植入的传递载体。其中包括许多可以在细胞规模上呈现的结构和生化线索,例如降解,粘附,机械信号,形貌以及生长因子的呈现,通常具有精确的时空控制。
  • 【腹腔内施用含有多种化疗剂的生物相容性透明质酸水凝胶,用于治疗结直肠腹膜癌。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijbiomac.2020.02.326 复制DOI
    作者列表:Luo J,Wu Z,Lu Y,Xiong K,Wen Q,Zhao L,Wang B,Gui Y,Fu S
    BACKGROUND & AIMS: :Colorectal peritoneal carcinomatosis (CRPC) is an advanced stage of colorectal cancer (CRC), which significantly decreases patient survival and quality of life. Here, the naturally occurring polysaccharide hyaluronic acid (HA) was used to prepare an injectable hydrogel and simultaneously deliver 5-fluorouracil (5-FU), cisplatin (DDP) and paclitaxel (PTX) microspheres for intraperitoneal CRPC chemotherapy. The drug-loaded HA hydrogel released the drugs in a sustained manner, and showed low toxicity both in vitro and in a mouse model of CRPC. Furthermore, direct injection of the drug-loaded HA hydrogel in the abdominal cavity of tumor-bearing mice significantly decreased tumor growth and liver/lung metastasis, along with decreasing the volume of ascites and inhibiting local intestinal infiltration of the tumor cells. Therefore, this novel multi-drug hydrogel delivery system may effectively clear CRPC tumors without any adverse effects when used in intraperitoneal chemotherapy.
    背景与目标: 结直肠腹膜癌 (CRPC) 是结直肠癌 (CRC) 的晚期,可显着降低患者的生存率和生活质量。在这里,天然存在的多糖透明质酸 (HA) 用于制备可注射的水凝胶,并同时递送5-氟尿嘧啶 (5-FU),顺铂 (DDP) 和紫杉醇 (PTX) 微球用于腹膜内CRPC化疗。载药的HA水凝胶以持续的方式释放药物,并且在体外和CRPC小鼠模型中均显示出低毒性。此外,在荷瘤小鼠的腹腔中直接注射载药HA水凝胶可显着减少肿瘤的生长和肝/肺转移,并减少腹水的体积并抑制肿瘤细胞的局部肠道浸润。因此,这种新颖的多药水凝胶递送系统可在腹膜内化疗中有效清除CRPC肿瘤,而不会产生任何不良影响。
  • 【BMP2-modified可注射水凝胶用于人牙周膜干细胞成骨分化。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-06911-8 复制DOI
    作者列表:Park SH,Kwon JS,Lee BS,Park JH,Lee BK,Yun JH,Lee BY,Kim JH,Min BH,Yoo TH,Kim MS
    BACKGROUND & AIMS: :This is the first report on the development of a covalently bone morphogenetic protein-2 (BMP2)-immobilized hydrogel that is suitable for osteogenic differentiation of human periodontal ligament stem cells (hPLSCs). O-propargyl-tyrosine (OpgY) was site-specifically incorporated into BMP2 to prepare BMP2-OpgY with an alkyne group. The engineered BMP2-OpgY exhibited osteogenic characteristics after in vitro osteogenic differentiation of hPLSCs, indicating the osteogenic ability of BMP2-OpgY. A methoxy polyethylene glycol-(polycaprolactone-(N3)) block copolymer (MC-N3) was prepared as an injectable in situ-forming hydrogel. BMP2 covalently immobilized on an MC hydrogel (MC-BMP2) was prepared quantitatively by a simple biorthogonal reaction between alkyne groups on BMP2-OpgY and azide groups on MC-N3 via a Cu(I)-catalyzed click reaction. The hPLSCs-loaded MC-BMP2 formed a hydrogel almost immediately upon injection into animals. In vivo osteogenic differentiation of hPLSCs in the MC-BMP2 formulation was confirmed by histological staining and gene expression analyses. Histological staining of hPLSC-loaded MC-BMP2 implants showed evidence of mineralized calcium deposits, whereas hPLSC-loaded MC-Cl or BMP2-OpgY mixed with MC-Cl, implants showed no mineral deposits. Additionally, MC-BMP2 induced higher levels of osteogenic gene expression in hPLSCs than in other groups. In conclusion, BMP2-OpgY covalently immobilized on MC-BMP2 induced osteogenic differentiation of hPLSCs as a noninvasive method for bone tissue engineering.
    背景与目标: : 这是关于共价骨形态发生蛋白2 (BMP2) 固定化水凝胶的开发的第一份报告,该水凝胶适用于人牙周膜干细胞 (hPLSCs) 的成骨分化。将O-炔丙基-酪氨酸 (OpgY) 位点特异性掺入BMP2中以制备具有炔基的BMP2-OpgY。工程BMP2-OpgY在hPLSCs体外成骨分化后表现出成骨特性,表明BMP2-OpgY的成骨能力。制备甲氧基聚乙二醇-(聚己内酯-(N3)) 嵌段共聚物 (MC-N3) 作为可注射原位形成水凝胶。通过Cu(I) 催化的点击反应,通过BMP2-OpgY上的炔烃基团与MC-N3上的叠氮化物基团之间的简单双正交反应,定量地制备共价固定在MC水凝胶 (MC-BMP2) 上的BMP2。负载hPLSCs的MC-BMP2在注射到动物中几乎立即形成水凝胶。通过组织学染色和基因表达分析证实了MC-BMP2制剂中hPLSCs的体内成骨分化。hPLSC负载的MC-BMP2植入物的组织学染色显示出矿化钙沉积的证据,而hPLSC负载的MC-Cl或BMP2-OpgY与MC-Cl混合,植入物未显示出矿物质沉积。此外,与其他组相比,MC-BMP2在hPLSCs中诱导了更高水平的成骨基因表达。总之,共价固定在MC-BMP2上的BMP2-OpgY可诱导hPLSCs的成骨分化,作为骨组织工程的非侵入性方法。
  • 【褐藻聚糖-壳聚糖水凝胶的制备及其在兔烧伤愈合促进剂中的应用。】 复制标题 收藏 收藏
    DOI:10.1248/bpb.31.2326 复制DOI
    作者列表:Sezer AD,Cevher E,Hatipoğlu F,Oğurtan Z,Baş AL,Akbuğa J
    BACKGROUND & AIMS: :Treatment of dermal wounds with macromolecular agents such as natural polymers is one of the research areas of the biomaterial science. Fucoidan is a sulphated polysaccharide which is commonly obtained from seaweeds. The great number of studies on the different pharmacological properties of fucoidan is present, but there is limited information about using of fucoidan in the treatment of dermal burns. The aim of this study was to prepare fucoidan-chitosan hydrogels and to investigate their treatment efficiency on dermal burns. Hydrogels were prepared by swelling the polymers in acidic solution and their swelling, mechanical (hardness, cohesiveness and adhesiveness) and bioadhesive properties were investigated. The viscosity and water absorption capacity of formulations increased with increase in the polymer concentration. In contrast to the cohesiveness results, the adhesiveness of hydrogels increased with the polymer concentration. The bioadhesion was changed between 0.012-0.142 mJ x cm(-2) and enhanced with addition of fucoidan into gel formulations. It was formed dermal burns on seven adult male New Zealand white rabbits and the optimum gel formulation applied on the wounds. Control and treatment group biopsy samples were taken on days 7, 14 and 21 and each burn wound site was evaluated histopathologically. No edema was seen in tested groups except control after 3 d treatment. After 7 d treatment, fibroplasia and scar were fixed on wounds treated with fucoidan-chitosan gel and fucoidan solution. The best regeneration on dermal papillary formation and the fastest closure of the wounds were observed in fucoidan-chitosan hydrogels after 14 d treatment.
    背景与目标: : 用天然聚合物等大分子制剂治疗皮肤伤口是生物材料科学的研究领域之一。岩藻依聚糖是一种硫酸化多糖,通常从海藻中获得。目前有关于岩藻依聚糖不同药理特性的大量研究,但是关于使用岩藻依聚糖治疗皮肤烧伤的信息有限。这项研究的目的是制备岩藻依聚糖-壳聚糖水凝胶,并研究其对皮肤烧伤的治疗效果。通过在酸性溶液中溶胀聚合物制备水凝胶,并研究了它们的溶胀,机械 (硬度,粘结性和粘合性) 和生物粘附性能。配方的粘度和吸水能力随着聚合物浓度的增加而增加。与内聚性结果相反,水凝胶的粘合性随聚合物浓度的增加而增加。生物粘附性在0.012-0.142 mJ × cm(-2) 之间改变,并通过向凝胶制剂中添加岩藻依聚糖而增强。在七只成年雄性新西兰白兔上形成皮肤灼伤,并在伤口上应用了最佳凝胶制剂。对照组和治疗组在第7、14和21天采集活检样本,并对每个烧伤伤口进行组织病理学评估。治疗3 d后,除对照组外,试验组未见水肿。治疗7 d后,在用岩藻糖-壳聚糖凝胶和岩藻糖溶液治疗的伤口上固定纤维增生和瘢痕。处理14 d后,在岩藻聚糖-壳聚糖水凝胶中观察到真皮乳头状形成的最佳再生和伤口的最快闭合。
  • 【适合缺陷的高强度仿生鱿鱼II型明胶水凝胶通过动态免疫调节和直接诱导方式促进了肋软骨的原位再生。】 复制标题 收藏 收藏
    DOI:10.1016/j.biomaterials.2020.119841 复制DOI
    作者列表:Dai M,Sui B,Hua Y,Zhang Y,Bao B,Lin Q,Liu X,Zhu L,Sun J
    BACKGROUND & AIMS: :Reconstructing segmental costal cartilage defects resulting from autologous cartilage grafts in plastic surgery remains a challenge. The present study focused on a biomimetic strategy for in situ costal cartilage regeneration that did not rely on an autogenous/xenogenous tissue graft. A multifunctional biomimetic SGII/HA-DN hydrogel based on a "chemical-curing, shaping, and light-curing" gelation system was developed and evaluated for its mechanical properties, clinical applications and biological functions. This hydrogel showed good suitability to repair defects and a high mechanical support strength (11 MPa, which is close to the natural strength of costal cartilage). Biologically, the hydrogel exhibited dual-immunomodulatory effects on the pro-inflammatory/anti-inflammatory phenotypes of neutrophils and M1/M2 macrophage polarization and subsequently promoted the chondrogenesis of cartilage stem/progenitor cells through both direct induction and indirect stimulation by the M2 macrophage-mediated TGF-β/Smad pathway. Furthermore, this SGII/HA-DN hydrogel could regulate the local microenvironment, inducing new costal cartilage regeneration in vivo. Our findings demonstrate that the newly developed multifunctional SGII/HA-DN hydrogel provides a strategy with high prospect for the biomimetic repair of segmental costal cartilage defects in clinical practice.
    背景与目标: : 在整形外科中重建自体软骨移植物导致的节段性肋软骨缺损仍然是一个挑战。本研究的重点是不依赖于自体/异种组织移植物的原位肋软骨再生的仿生策略。开发了一种基于 “化学固化,整形和光固化” 凝胶系统的多功能仿生SGII/HA-DN水凝胶,并对其机械性能,临床应用和生物学功能进行了评估。该水凝胶显示出良好的修复缺陷的适用性和高的机械支撑强度 (11 MPa,接近肋软骨的自然强度)。生物学上,水凝胶对中性粒细胞的促炎/抗炎表型和M1/M2巨噬细胞极化表现出双重免疫调节作用,随后通过M2巨噬细胞介导的TGF-β/Smad途径的直接诱导和间接刺激促进软骨干/祖细胞的软骨形成。此外,该SGII/HA-DN水凝胶可以调节局部微环境,在体内诱导新的肋软骨再生。我们的发现表明,新开发的多功能SGII/HA-DN水凝胶为临床实践中节段性肋软骨缺损的仿生修复提供了一种前景广阔的策略。
  • 【使用基于Pluronic-Gantrez缀合物的热敏水凝胶对细菌抗原进行鼻内递送系统。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2020.119154 复制DOI
    作者列表:Pastor Y,Ting I,Martínez AL,Irache JM,Gamazo C
    BACKGROUND & AIMS: :Thermosensitive hydrogels have been studied as feasible needle-avoidance alternative to vaccine delivery. In this work, we report the development of a new thermal-sensitive hydrogel for intranasal vaccine delivery. This delivery system was formulated with a combination of the polymer Gantrez® AN119 and the surfactant Pluronic® F127 (PF127), with a high biocompatibility, biodegradability and immunoadjuvant properties. Shigella flexneri outer membrane vesicles were used as the antigen model. A stable and easy-to-produce thermosensitive hydrogel which allowed the incorporation of the OMV-antigenic complex was successfully synthetized. A rapid gel formation was achieved at body temperature, which prolonged the OMV-antigens residence time in the nasal cavity of BALB/c mice when compared to intranasal delivery of free-OMVs. In addition, the bacterial antigens showed a fast release profile from the hydrogel in vitro, with a peak at 30 min of incubation at 37 °C. Hydrogels appeared to be non-cytotoxic in the human epithelial HeLa cell line and nose epithelium as well, as indicated by the absence of histopathological features. Immunohistochemical studies revealed that after intranasal administration the OMVs reached the nasal associated lymphoid tissue. These results support the use of here described thermosensitive hydrogels as a potential platform for intranasal vaccination.
    背景与目标: : 已经研究了热敏水凝胶作为疫苗递送的可行避免针的替代方法。在这项工作中,我们报告了用于鼻内疫苗递送的新型热敏水凝胶的开发。该输送系统是由聚合物Gantrez的组合配制而成的。®AN119和表面活性剂Pluronic®F127 (PF127),具有较高的生物相容性、生物降解性和免疫佐剂特性。福氏志贺菌外膜囊泡被用作抗原模型。成功合成了一种稳定且易于生产的热敏水凝胶,该凝胶允许掺入OMV抗原复合物。在体温下实现了快速的凝胶形成,与鼻内递送游离OMV相比,延长了OMV抗原在BALB/c小鼠鼻腔中的停留时间。此外,细菌抗原在体外显示出从水凝胶的快速释放曲线,在37 °C孵育30分钟时达到峰值。水凝胶在人上皮HeLa细胞系和鼻子上皮中似乎也是非细胞毒性的,这由缺乏组织病理学特征所表明。免疫组织化学研究表明,鼻内给药后,omv到达鼻相关淋巴组织。这些结果支持使用此处描述的热敏水凝胶作为鼻内疫苗接种的潜在平台。
  • 【微微流体技术在多糖水凝胶中封装和支持活的人间充质干细胞的应用。】 复制标题 收藏 收藏
    DOI:10.3390/ijms19071952 复制DOI
    作者列表:Nativel F,Renard D,Hached F,Pinta PG,D'Arros C,Weiss P,Le Visage C,Guicheux J,Billon-Chabaud A,Grimandi G
    BACKGROUND & AIMS: :Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells during and after their injection by encapsulation in a hydrogel using a droplet millifluidics technique. A biocompatible, self-hardening biomaterial composed of silanized-hydroxypropylmethylcellulose (Si-HPMC) hydrogel was used and dispersed in an oil continuous phase. Spherical particles with a mean diameter of 200 μm could be obtained in a reproducible manner. The viability of the encapsulated hASCs in the Si-HPMC particles was 70% after 14 days in vitro, confirming that the Si-HPMC particles supported the diffusion of nutrients, vitamins, and glucose essential for survival of the encapsulated hASCs. The combination of droplet millifluidics and biomaterials is therefore a very promising method for the development of new cellular microenvironments, with the potential for applications in biomedical engineering.
    背景与目标: : 人脂肪来源的基质细胞 (hASCs) 因其免疫调节和抗炎特性而广为人知。这项研究提出了一种使用液滴毫流体技术通过将细胞封装在水凝胶中保护细胞的方法。使用了由硅烷化的羟丙基甲基纤维素 (Si-HPMC) 水凝胶组成的生物相容性,自硬化生物材料,并将其分散在油连续相中。可以以可再现的方式获得平均直径为200微米的球形颗粒。在体外14天后70% si-hpmc颗粒中包封的hasc的生存力,证实si-hpmc颗粒支持对包封的hasc的存活所必需的营养物、维生素和葡萄糖的扩散。因此,液滴毫流体和生物材料的结合是开发新的细胞微环境的非常有前途的方法,具有在生物医学工程中应用的潜力。
  • 【聚乙烯醇/粘土纳米复合水凝胶伤口敷料的体内和细胞毒性测定。】 复制标题 收藏 收藏
    DOI:10.1163/092050610X497881 复制DOI
    作者列表:Sirousazar M,Kokabi M,Hassan ZM
    BACKGROUND & AIMS: :In the present work, a nanocomposite hydrogel wound dressing was prepared on the basis of poly(vinyl alcohol) using organically-modified montmorillonite as nanoclay by the freezing-thawing cyclic method. In vivo assays were performed to evaluate its performance as an applicable wound dressing on animals. It showed an improved healing process for wounds covered by the prepared nanocomposite hydrogel compared with control wounds covered by sterile gauze. Significant improvements, such as better creation of moist surfaces on the wound with less scar formation, shorter duration of healing operation and better closing of the wound edges with enhanced tensile properties of the healed wound, i.e., tensile strength and elongation-at-break, were observed using the prepared nanocomposite hydrogel in comparison to the sterile gauze. An in vitro cytotoxic assay was also utilized to determine the biocompatibility of the prepared nanocomposite hydrogel. It showed that the prepared nanocomposite hydrogel is non-toxic and can be used as a biocompatible wound dressing in practical wound management.
    背景与目标: : 在目前的工作中,使用有机改性的蒙脱土作为纳米粘土,以聚乙烯醇为基础,通过冻融循环法制备了纳米复合水凝胶伤口敷料。进行了体内测定,以评估其作为动物伤口敷料的性能。与无菌纱布覆盖的对照伤口相比,制备的纳米复合水凝胶覆盖的伤口的愈合过程得到了改善。显著的改善,例如在伤口上更好地形成潮湿的表面,更少的疤痕形成,更短的愈合手术时间和更好地闭合伤口边缘,增强愈合伤口的拉伸性能,即拉伸强度和断裂伸长率,与无菌纱布相比,使用制备的纳米复合水凝胶进行了观察。还利用体外细胞毒性测定法确定所制备的纳米复合水凝胶的生物相容性。结果表明,所制备的纳米复合水凝胶无毒,可作为生物相容性伤口敷料用于实际伤口处理。

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