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Synthesis and characterization of biocompatible-nanohydroxyapatite crystals obtained by a modified sol-gel processing. 改性溶胶-凝胶法制备生物相容性纳米羟基磷灰石晶体的合成与表征。
Pub Date : 2012-04-01 DOI: 10.4161/biom.20379
Ignacio A Figueroa, Omar Novelo-Peralta, Carlos Flores-Morales, Rodrigo González-Tenorio, M Cristina Piña-Barba

A modified sol-gel process for synthesizing nanocrystalline hydroxyapatite powders (nHA) for biomedical applications, using tetrahydrated calcium nitrate [Ca(NO(3))(2)∙4H(2)O] and phosphorous pentoxide [P(2)O(5)] as precursor, is presented and discussed. The powders were washed and heat-treated at different temperatures and then characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The total process time reached with this modified process was less than 16 h. The results showed that there was an increment in size of the HA nanocrystals (nHA) when treated at different temperatures, ranging from 30 nm for the sample treated at 600°C to 500 nm for the sample heat-treated at 1,200°C.

提出并讨论了以四水合硝酸钙[Ca(NO(3))(2)∙4H(2)O]和五氧化二磷[P(2)O(5)]为前驱体,溶胶-凝胶法制备生物医学用纳米羟基磷灰石粉末(nHA)的改进工艺。对粉末进行洗涤和不同温度的热处理,并用x射线衍射(XRD)、扫描电镜(SEM)和透射电镜(TEM)对其进行表征。结果表明,在不同温度下处理的HA纳米晶体(nHA)的尺寸都有增加,从600°C处理的样品的30 nm到1200°C热处理的样品的500 nm不等。
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引用次数: 7
In vitro degradation and release characteristics of spin coated thin films of PLGA with a "breath figure" morphology. 具有 "呼吸图 "形态的聚乳酸(PLGA)旋涂薄膜的体外降解和释放特性。
Pub Date : 2012-04-01 DOI: 10.4161/biom.20390
Thiruselvam Ponnusamy, Louise B Lawson, Lucy C Freytag, Diane A Blake, Ramesh S Ayyala, Vijay T John

Poly (lactic-co-glycolic acid) (PLGA) coatings on implant materials are widely used in controlled drug delivery applications. Typically, such coatings are made with non-porous films. Here, we have synthesized a thin PLGA film coating with a highly ordered microporous structure using a simple and inexpensive water templating "breath figure" technique. A single stage process combining spin coating and breath figure process was used to obtain drug incorporated porous thin films. The films were characterized by scanning electron microscope (SEM) to observe the surface and bulk features of porosity and also, degradation pattern of the films. Moreover, the effect of addition of small amount of poly (ethylene glycol) (PEG) into PLGA was characterized. SEM analysis revealed an ordered array of ~2 µm sized pores on the surface with the average film thickness measured to be 20 µm. The incorporation of hydrophilic poly (ethylene glycol) (PEG) enhances pore structure uniformity and facilitates ingress of water into the structure. A five week in vitro degradation study showed a gradual deterioration of the breath figure pores. During the course of degradation, the surface pore structure deteriorates to initially flatten the surface. This is followed by the formation of new pinprick pores that eventually grow into a macroporous film prior to film breakup. Salicylic acid (highly water soluble) and Ibuprofen (sparingly water soluble) were chosen as model drug compounds to characterize release rates, which are higher in films of the breath figure morphology rather than in non-porous films. The results are of significance in the design of biodegradable films used as coatings to modulate delivery.

植入材料上的聚(乳酸-共聚乙醇酸)(PLGA)涂层被广泛应用于可控给药领域。通常情况下,这种涂层是用无孔薄膜制成的。在这里,我们采用简单廉价的水模板 "呼吸图 "技术合成了具有高度有序微孔结构的 PLGA 薄膜涂层。我们采用旋涂和呼吸图工艺相结合的单阶段工艺,获得了含有药物的多孔薄膜。利用扫描电子显微镜(SEM)对薄膜进行了表征,以观察多孔结构的表面和体积特征,以及薄膜的降解模式。此外,还对在聚乳酸乙二醇(PLGA)中添加少量聚乙二醇(PEG)的效果进行了表征。扫描电子显微镜分析表明,薄膜表面有序排列着 ~2 微米大小的孔隙,薄膜平均厚度为 20 微米。亲水性聚乙二醇(PEG)的加入增强了孔隙结构的均匀性,并有利于水分进入孔隙结构。为期五周的体外降解研究表明,呼吸图孔会逐渐退化。在降解过程中,表面孔隙结构会恶化,最初会使表面变平。随后会形成新的针孔,最终在薄膜破裂前形成大孔薄膜。我们选择了水杨酸(高水溶性)和布洛芬(稀水溶性)作为模型药物化合物来表征释放率,在呼吸图形态的薄膜中释放率要高于无孔薄膜。这些结果对设计用作涂层的可生物降解薄膜以调节给药具有重要意义。
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引用次数: 0
Realization of a poro-elastic ultrasound replica of pulmonary tissue. 实现肺组织的孔弹性超声波复制品。
Pub Date : 2012-01-01 DOI: 10.4161/biom.19835
Andrea Spinelli, Bruna Vinci, Annalisa Tirella, Marco Matteucci, Luna Gargani, Arti Ahluwalia, Claudio Domenici, Eugenio Picano, Piero Chiarelli

In this work we describe the fabrication of a biocompatible hydrophilic scaffold composed of cross-linked gelatin that mimics the porous three-dimensional structure of pulmonary tissue as well as its water content and mechanical properties. The lung replica also reproduces the characteristic sonographic signs of pulmonary interstitial syndrome, the B-lines or ultrasound lung comets.

在这项工作中,我们描述了一种由交联明胶组成的生物相容性亲水支架的制作过程,它模仿了肺组织的多孔三维结构及其含水量和机械性能。该肺复制品还再现了肺间质综合征的特征性声学标志--B 线或超声肺彗星。
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引用次数: 0
Maintenance of α(1)-antitrypsin activity by means of co-application of hypochlorous acid-scavengers in vitro and in the supernatant of polymorphonuclear leukocytes: as a basis for a new drug delivery approach. 通过在体外和多形核白细胞上清中共同应用次氯酸清除剂维持α(1)-抗胰蛋白酶活性:作为一种新的药物递送方法的基础。
Pub Date : 2012-01-01 DOI: 10.4161/biom.19190
Maria Schönberg, Uta Reibetanz, Sophie Rathmann, Jacqueline Lessig

Tissue destruction, pain and loss of function in chronically inflamed tissues can result from noxious agents released from myeloperoxidase (MPO) and its highly reactive product hypochlorous acid (HOCl) or proteases such as neutrophil elastase (NE). Currently there exists a high demand for medications that provide gentle treatments, free from side effects inherent in those prescribed today. One method to circumvent side effects is through the use of locally applied drug delivery. In contrast to systemic therapy, the main advantages of transport systems are the low dosages of drug with a time-controlled delivery. The aim of this study was to ascertain interactions of NE and its inhibitor α(1)-antitrypsin (AT), the influence of hypochlorous acid (HOCl), as well as its scavengers, in order to define an effective mixture of drugs acting in a synergistic way which can be applied by means of drug delivery systems. These investigations determine the effective amounts of AT/HOCl-scavengers that drug mixtures need for delivery under inflammatory conditions in order to prevent tissue damage. AT was shown to inhibit NE in a dose-dependent manner, whereas a physiological concentration of 1.14 µM AT caused a significant NE inhibition (78%, pH 7.5). The concomitant existence of MPO/HOCl inactivated AT in a dose-dependent manner as well. To regain AT efficacy, HOCl-scavengers, such as L-methionine, α-aminosalicylic acid and cefoperazone were additionally applied. Finally, AT was assembled as surface layer onto layer-by-layer biopolymer-coated microcarriers and carrier phagocytosis by polymorphonuclear leukocytes could be shown.

髓过氧化物酶(MPO)及其高活性产物次氯酸(HOCl)或蛋白酶(如中性粒细胞弹性酶(NE))释放的有害物质可导致慢性炎症组织的组织破坏、疼痛和功能丧失。目前,人们对温和治疗的药物有很高的需求,这些药物没有目前处方中固有的副作用。避免副作用的一种方法是使用局部用药。与全身治疗相比,运输系统的主要优点是低剂量的药物和时间控制的递送。本研究的目的是确定NE与其抑制剂α(1)-抗胰蛋白酶(AT)的相互作用,次氯酸(HOCl)及其清除剂的影响,以便确定一种有效的药物混合物,以协同方式起作用,可以通过药物输送系统应用。这些研究确定了药物混合物在炎症条件下递送以防止组织损伤所需的AT/ hocl清除剂的有效量。结果表明,AT以剂量依赖的方式抑制NE,而生理浓度为1.14µM的AT可显著抑制NE (78%, pH 7.5)。同时存在的MPO/HOCl也以剂量依赖的方式使AT失活。为了恢复AT疗效,在此基础上加用l-蛋氨酸、α-氨基水杨酸和头孢哌酮等hocl清除剂。最后,AT作为表面层被组装到一层一层的生物聚合物包被的微载体上,可以显示载体被多形核白细胞吞噬。
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引用次数: 8
Resolving the CaP-bone interface: a review of discoveries with light and electron microscopy. 解析CaP-bone界面:光镜和电子显微镜发现综述。
Pub Date : 2012-01-01 DOI: 10.4161/biom.20062
Kathryn Grandfield, Anders Palmquist, Håkan Engqvist, Peter Thomsen

It has long been known that the interfacial relationship between synthetic materials and tissue is influential in the success of implant materials. Instability at the implant interface has been shown, in some cases, to lead to complete implant failure. Bioceramics, and in particular calcium phosphates, form a large fraction of the implantable devices on the market today due to the biocompatibility they exhibit in contact with bone and tooth-like tissues. The characterization of such bioceramic-tissue interfaces has played a crucial role in understanding the behavior of bioceramics in vivo. In this review, we shed light on the preparation methods, technological approaches and key advances in resolving the interface between calcium phosphate bioceramics and bone, and share a future outlook on this field.

人工合成材料与组织之间的界面关系是影响植入材料成功与否的重要因素。在某些情况下,种植体界面的不稳定性会导致种植体完全失效。生物陶瓷,特别是磷酸钙,由于其在与骨和齿状组织接触时表现出的生物相容性,在当今市场上的植入式装置中占很大比例。这种生物陶瓷-组织界面的表征对于理解生物陶瓷在体内的行为起着至关重要的作用。本文综述了磷酸钙生物陶瓷的制备方法、技术途径和解决磷酸钙生物陶瓷与骨界面的关键进展,并展望了该领域的发展前景。
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引用次数: 8
Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges. 再生疗法和组织工程治疗终末期心力衰竭:新进展和挑战。
Pub Date : 2012-01-01 DOI: 10.4161/biom.19429
G T Finosh, Muthu Jayabalan

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

通过再生疗法和组织工程实现心肌再生正成为终末期心力衰竭患者的一种有前景的治疗方式。本文就心肌组织再生的研究进展和面临的挑战作一综述。讨论了各种细胞来源、钙离子和细胞因子在再生治疗功能表现中的作用。本文还讨论了组织工程的发展以及组织基质/支架、细胞黏附和血管化在心脏组织植入物组织工程中的作用。
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引用次数: 44
Implanted neonatal human dermal fibroblasts influence the recruitment of endothelial cells in mice. 植入新生人真皮成纤维细胞对小鼠内皮细胞募集的影响。
Pub Date : 2012-01-01 DOI: 10.4161/biom.20063
Susana G Guerreiro, Christoph Brochhausen, Rita Negrão, Mário A Barbosa, Ronald E Unger, C James Kirkpatrick, Raquel Soares, Pedro L Granja

The vascularization of new tissue within a reasonable time is a crucial prerequisite for the success of different cell- and material-based strategies. Considering that angiogenesis is a multi-step process involving humoral and cellular regulatory components, only in vivo assays provide the adequate information about vessel formation and the recruitment of endothelial cells. The present study aimed to investigate if neonatal human dermal fibroblasts could influence in vivo neovascularization. Results obtained showed that fibroblasts were able to recruit endothelial cells to vascularize the implanted matrix, which was further colonized by murine functional blood vessels after one week. The vessels exhibited higher levels of hemoglobin, compared with the control matrix, implanted without fibroblasts, in which no vessel formation could be observed. No significant differences were detected in systemic inflammation. The presence of vessels originated from the host vasculature suggested that host vascular response was involved, which constitutes a fundamental aspect in the process of neovascularization. Fibroblasts implanted within matrigel increased the presence of endothelial cells with positive staining for CD31 and for CD34 and the production of collagen influencing the angiogenic process and promoting the formation of microvessels. New strategies in tissue engineering could be delineated with improved angiogenesis using neonatal fibroblasts.

在合理的时间内新组织的血管化是不同的细胞和材料为基础的策略成功的关键先决条件。考虑到血管生成是一个涉及体液和细胞调节成分的多步骤过程,只有体内试验才能提供有关血管形成和内皮细胞募集的充分信息。本研究旨在探讨新生儿真皮成纤维细胞是否能影响体内新生血管的形成。结果表明,成纤维细胞能够募集内皮细胞,使植入的基质血管化,一周后再被小鼠功能血管定植。与未植入成纤维细胞的对照基质相比,血管表现出更高的血红蛋白水平,在对照基质中没有观察到血管形成。全身性炎症无明显差异。来源于宿主脉管系统的血管的存在表明参与了宿主血管反应,这是新生血管形成过程中的一个基本方面。植入基质内的成纤维细胞增加了CD31和CD34染色阳性的内皮细胞的存在,并增加了胶原的产生,影响血管生成过程,促进微血管的形成。利用新生儿成纤维细胞改善血管生成,可以描绘组织工程的新策略。
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引用次数: 15
Development of affinity-based delivery of NGF from a chondroitin sulfate biomaterial. 硫酸软骨素生物材料亲和递送NGF的研究进展。
Pub Date : 2011-10-01 DOI: 10.4161/biom.18791
Karen Chao Butterfield, Aaron W Conovaloff, Alyssa Panitch

Chondroitin sulfate is a major component of the extracellular matrix in both the central and peripheral nervous systems. Chondroitin sulfate is upregulated at injury, thus methods to promote neurite extension through chondroitin sulfate-rich matrices and synthetic scaffolds are needed. We describe the use of both chondroitin sulfate and a novel chondroitin sulfate-binding peptide to control the release of nerve growth factor. Interestingly, the novel chondroitin sulfate-binding peptide enhances the controlled release properties of the chondroitin sulfate gels. While introduction of chondroitin sulfate into a scaffold inhibits primary cortical outgrowth, the combination of chondroitin sulfate, chondroitin sulfate-binding peptide and nerve growth factor promotes primary cortical neurite outgrowth in chondroitin sulfate gels.

硫酸软骨素是中枢和周围神经系统细胞外基质的主要成分。硫酸软骨素在损伤时上调,因此需要通过富含硫酸软骨素的基质和合成支架促进神经突延伸的方法。我们描述了使用硫酸软骨素和一种新的硫酸软骨素结合肽来控制神经生长因子的释放。有趣的是,新型硫酸软骨素结合肽增强了硫酸软骨素凝胶的控释特性。在支架中引入硫酸软骨素可抑制皮层的初生生长,而硫酸软骨素、硫酸软骨素结合肽和神经生长因子的结合可促进硫酸软骨素凝胶中皮层神经突的初生生长。
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引用次数: 25
Factorial design-based development of measlamine microspheres for colonic delivery. 基于因子设计的甲胺微球结肠给药研究。
Pub Date : 2011-10-01 DOI: 10.4161/biom.18461
Vikas Jain, Dayal Prasad, Deepika Jain, Santosh Kumar Mishra, Ranjit Singh

For treating colonic diseases, conventional oral drug delivery systems are not effective, as they fail to reach the appropriate site of action. Thus, there is a need to develop effective and safe therapy for the treatment of colonic disorders. The aim of the present study was to design a colon-specific delivery system for an anti-inflammatory drug, mesalamine, with minimal degradation and optimum delivery of the drug with relatively higher local concentration, which may provide more effective therapy for inflammatory bowel disease including Crohn disease and ulcerative colitis. Factorial designs (four factors and two levels) for eudragit S-100 (pH-dependent polymer)-coated, pectin (natural polysaccharides)-based microspheres of mesalamine were constructed and conducted in a fully randomized manner to study all possible combinations. Based on the desirability function formulation, F14 was found to be the best formulation. The overall desirability coefficient of formulation F14 was found to be 0.825. The formulation F14 was subjected to in vitro release studies, and the results were evaluated kinetically and statistically. The microspheres started releasing the drug at the beginning of 7th hour, which corresponds to the arrival time at proximal colon. The cumulative percent drug release for formulation F14 at the end of 16 h was found to be 98%. The release kinetics showed that the release followed the Higuchi model, and the main mechanism of drug release was diffusion. The study presents a new approach for colon-specific drug delivery.

对于治疗结肠疾病,传统的口服给药系统是无效的,因为它们不能到达适当的作用部位。因此,有必要开发有效和安全的治疗结肠疾病的方法。本研究的目的是设计一种消炎药美沙拉胺的结肠特异性递送系统,以最小的降解和相对较高的局部浓度的最佳递送药物,这可能为包括克罗恩病和溃疡性结肠炎在内的炎症性肠病提供更有效的治疗。构建了四因素两水平的析因设计(四因素两水平),对桉木糖S-100 (ph依赖性聚合物)包被,果胶(天然多糖)为基础的美沙拉胺微球进行了完全随机的设计,以研究所有可能的组合。根据期望函数公式,确定F14为最佳配方。配方F14的总体理想系数为0.825。对制剂F14进行体外释放实验,并对实验结果进行动力学和统计学评价。微球在第7小时开始释放药物,这与到达近端结肠的时间相对应。F14制剂16 h的累积释药率为98%。释放动力学表明,该药物的释放符合Higuchi模型,其主要释放机制为扩散。本研究提出了一种结肠特异性给药的新方法。
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引用次数: 13
Designing polysaccharide-based antibacterial biomaterials for wound healing applications. 设计用于伤口愈合的多糖类抗菌生物材料。
Pub Date : 2011-10-01 DOI: 10.4161/biom.19005
Amita Chhatri, Jaya Bajpai, A K Bajpai

In this study, the development and characterization of novel polymer blends based on chitosan-poly (vinyl alcohol) and physically cross-linked by freeze-thaw method for possible use in a variety of biomedical application is reported. The present investigation deals with designing savlon-loaded blend hydrogels (coined as cryogels) of poly (vinyl alcohol) (PVA) and chitosan by repeated freeze-thaw method and their characterization by SEM and FTIR techniques. The FTIR spectra clearly reveal that savlon-loaded chitosan and PVA blends are bonded together through hydrogen bonding. The SEM analysis suggests that cryogels show a well-defined porous morphology. The prepared cryogels were also investigated for swelling and deswelling behaviors. The results reveal that both the swelling and deswelling behaviors greatly depend on factors like chemical composition of the cryogels, number of freeze-thaw cycles, pH and temperature of the swelling bath. The savlon-loaded blends were also investigated for their in vitro blood compatibility and antibacterial activity.

在本研究中,以壳聚糖-聚乙烯醇为基础,通过冻融法进行物理交联的新型聚合物共混物的开发和表征,有望用于各种生物医学应用。采用反复冻融法设计了聚乙烯醇(PVA)和壳聚糖(壳聚糖)共混水凝胶,并用扫描电镜(SEM)和红外光谱(FTIR)对其进行了表征。FTIR光谱清楚地表明,负载savlon的壳聚糖和PVA共混物通过氢键结合在一起。扫描电镜分析表明,冷冻剂表现出明确的多孔形态。研究了所制备的冷冻液的溶胀和溶胀行为。结果表明,冻融液的化学成分、冻融循环次数、pH值和温度对溶胀和溶胀行为都有很大的影响。并对其体外血液相容性和抗菌活性进行了研究。
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引用次数: 32
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