中国科技论文统计源期刊 中文核心期刊
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖
, 潘孝汇
, PAN Xiaohui
酸性成纤维细胞生长因子(aFGF )是第2个被分离纯化的成纤维细胞因子(FGFs )家族成员。aFGF 具有广泛的生理功能,可促进组织创伤修复、血管生成、神经营养再生等,因而受到国内外学者的高度重视。但aFGF生物半衰期短,在体内容易被降解,极大限制了其临床应用。为改善 aFGF 易被水解、不稳定的缺点,可用性能良好的载体材料包载 aFGF 以获得缓控释药物制剂。该文就目前开展的各类aFGF相关载体材料的实验和应用研究进行综述,概括相关研究结果优劣和发展趋势。
Acidic fibroblast growth factor (aFGF), which is isolated and purified as the second member of fibroblast growth factor family.Because of its extensive physiological function, such as promoting wound healing,angiogenesis,nerve tissue nutrition and repair, it has attracted close attention.Nonetheless, the short half-life and easy degradation of aFGF limits the clinical application.In order to improve the hydrolysis and instability of aFGF, the study on aFGF controlled-release preparation through a good biological material carrier has become a research focus recently.Herein, we reviewed and discussed the several related biological material carrier experiments and application, and summarized the advantages, limitations and trends of progress.
酸性成纤维细胞生长因子 (acidic fibroblast growth factor,aFGF )主要分布在脑组织和肾脏,1984 年从牛脑中分离纯化得到。aFGF 对来源于神经外胚层及中胚层的细胞,有促分裂作用,能促进创面肉芽组织生长,诱导毛细血管胚芽形成[1]。同时具有抑制胶原蛋白过量沉积、避免形成病理性瘢痕的功能,临床促愈合疗效显著。尽管其在体内的含量甚微,但生理效能相当广泛,可用于临床烧伤、创伤、神经损伤及脑移植等领域[2]。但aFGF 作为一种蛋白多肽,性质非常不稳定,在体内易被蛋白酶水解。同时,其应用于创面修复时,创面滞留时间很短,病灶部位很难达到正常的治疗剂量,需要反复给药,增加风险和成本[3]。因此,在创面治疗过程中利用生物材料载体包载 aFGF ,提高其在体内的稳定性,维持生物活性,实现 aFGF 在病灶部位的可控释放,一方面增强疗效,另一方面避免反复给药,降低感染风险,越来越引起研究人员的关注。
aFGF 由154个氨基酸残基组成,具有一个β型三叶草模体 (motif ) (由 3 个相同的折叠模式组装而成,而该折叠模式又由 4 个延伸β折叠组装而成,由于缺乏α螺旋,结构类似于一个假性三轴对称体)[4]。这样的结构与 aFGF 生理功能密切相关。
aFGF 的生理功能和生物学效应丰富多样,能激活成纤维细胞生长因子受体(fibroblast growth factor receptor,FGFR)的胞质部酪氨酸的自身磷酸化,实现对中胚层及神经外胚层来源细胞的增殖、分化及功能的影响,在促进机体的生长发育、修复组织损伤等方面发挥重要作用。
aFGF作为一种酸性蛋白质类药物,在体内极不稳定,生物半衰期短,生物活性具有剂量依赖性。这些特点制约着aFGF 进一步体内应用的研究及临床创伤修复药物的研发。特殊的载体材料包载 aFGF,一方面能够有效保护 aFGF分子,提高其耐热性和稳定性。另一方面能有效控制aFGF分子的释放速度,特别在创面修复中,可延长 aFGF 在创面的滞留时间,避免多次给药造成的污染和医疗成本增高,实现可控释放 aFGF 的目的。
在 FGFs 家族中,bFGF 载体材料的研究较多。由于aFGF与 bFGF 具有高度同源性,笔者未见两者在载体选择性上有差异性报道。因此,笔者总结部分已报道用于aFGF的载体材料,并对部分 bFGF 载体存在的研究价值进行比较和展望。
泊洛沙姆是一种聚氧乙烯-聚氧丙烯-聚氧乙烯 (PEO-PPO-PEO ) 三嵌段共聚物[12],具有生物相容性良好、刺激性小、毒性低的特性。同时,其特殊的反向热敏胶凝性(在4~10 ℃时为液态,当温度升高至室温或体温时形成凝胶状)使之成为凝胶材料中的一大研究热点,已被广泛用于经皮给药、黏膜给药等多个给药系统[13]。
以泊洛沙姆水凝胶包载 aFGF,提高 aFGF 的稳定性并有效控制aFGF的释放速度,从而改善临床创面愈合效率具有很强的可实施性。WU等[14]开发了一种热敏性肝素-泊洛沙姆(Heparin-Poloxamer,HP)水凝胶,用以负载和递送 aFGF,用于体内伤口愈合。他们通过广泛的体内试验,系统评估了使用含有和不含有HP水凝胶的伤口愈合效率。实验表明所有含有和不含有 HP水凝胶组具有比对照组更好的伤口愈合率,并且HP-aFGF 水凝胶显示出其优异的愈合活性。
LIU等[15]利用短肽 RADA 在水中自组装成纳米纤维[16],并形成水凝胶,用以包裹aFGF。RADA 自组装肽的纤维直径通常在10~20 nm[17],形成的自组装短肽水凝胶的孔径大小和普通球形蛋白质的尺度 (1~100 nm) 接近,因此可以实现缓慢释放所包裹蛋白质的效果。LIU 等[15]通过紫外分光光度计对不同时间点释放的 aFGF 含量进行检测并依据其含量绘制了释放曲线,结果表明短肽水凝胶可有效控制 aFGF 的释放速度。此外,短肽水凝胶的微环境十分接近蛋白质在体内的环境,因此不会导致aFGF结构明显改变,并能一定程度上保护其不被水解。
自组装纳米纤维具有非常高的水含量(>99.5%,M/V),能形成高度交织纳米纤维支架凝胶,适合细胞迁移,并诱导和调节各种细胞因子和生长[18]。同时,其具有低毒、生物相容性好等特点。虽然目前 RADA 水凝胶缓释系统的研究仍处于起步阶段,其作为载体制成凝胶敷料的安全性还有待继续研究,但相信通过深入研究和开发后,RADA 自组装纳米纤维水凝胶将在组织再生及修复领域具有巨大的应用前景。
脂质体 (liposomes) 作为载体材料包载药物的研究是目前的一大热点,可制备包裹多种不同极性药物的脂质体,提高药物稳定性,同时实现缓慢释药[19]。此外,脂质体是类似生物膜的泡囊,可降低全身不良反应[20],具有细胞亲和性和靶向性,抵抗耐药性[21,22]。
随着多种新型脂质体的研制,国内外对脂质体包载 aFGF 类药物的研究也逐步开展。王倩等[23]采用 pH 梯度法来制备aFGF脂质体。通过测定其体外释药动力学发现,与aFGF原液相比,制备的 aFGF 脂质体在稳定性、包封率、缓释性上均得到一定程度的提高。
脂质体作为包载材料存在巨大的开发潜力和应用价值,但是其递药系统产业化是制约其发展的瓶颈,有待未来进一步突破。
在临床创伤修复中,aFGF 的复合胶原海绵与aFGF溶液的外搽或喷剂相比,具有更显著的治疗效果,这主要因为[26]:①两者冻干形成海绵体,能将 aFGF 固定于载体上,可以减缓 aFGF 在创面的流失;②将 aFGF 包裹于胶原海绵,能使之随胶原海绵的分解而逐步释放,起到缓释作用。
纳米银是通过纳米技术实现银的纳米化而成的新型抗菌产品。纳米银杀菌机制与化学合成的抗菌药不同,其逐渐释放的动态活性银离子能结合带负电荷的菌体蛋白质,使之变形沉淀,并同时与酶的巯基结合,阻断细菌呼吸酶系统[30]。因而具有不易耐药、广谱杀菌的作用,是一种安全性高、效能持久的长效新型抗菌药。
朱东来等[31]进行了 aFGF 的相关临床疗效研究,将纳米银敷料与重组人酸性成纤维细胞生长因子(recombinant human acidic fibroblast growth factor,rhaFGF)联合用于临床深Ⅱ度烧伤创面的治疗中,结果显示治疗组创面愈合率明显提高且感染率显著降低。
利用纳米银敷料包载 aFGF 的实验临床疗效良好,并且对于创面无刺激性、无毒副作用、安全性高、实验方法安全简便[32],为开发具有优良特性的临床创面敷料提供了新的思路。
生物敷料 A 的主要成分为胶原纤维、微量元素、黏蛋白、类黏蛋白,是一种通过次价键和酰氨键与糖昔键胶联,与胶原纤维形成无纺布结构的生物胶原蛋白膜[33],被认为是一种理想的创面覆盖物。相比于脂棉纱布、棉球等传统敷料,可保持伤口干燥,具有物理隔离功能[34]。目前,生物辅料主要用于烧伤、褥疮、糖尿病足等慢性溃疡[35],与以下特性密切相关:①具有良好的生物相容性,可暂时封闭创面,保持创面清洁干燥,不会引起中毒、病变等[36];②能与创面紧密贴合,减少细菌等侵袭引发的创面感染;③具有良好的透水、透气功能,可减少创面积液的形成[37]。
王雪莹等[38]应用生物敷料联合rhaFGF 治疗大面积、重度烧伤。研究发现通过应用生物敷料A联合rhaFGF 治疗后,有效地减轻患者的疼痛,减少了创面的感染,获得良好的治疗效果。
微球(microspheres)是利用天然或合成的高分子材料,包嵌药物而成的的微小球形囊状物[40]。其具有提高药物稳定性、延长药物疗效、减少不良反应等优点[41]。由于微球性质稳定、生物相容性良好,因此对溶解度小和渗透慢的甾体药物及生物活性易丧失的多肽类药物具有良好的使用价值。
bFGF 缓释微球在微球给药系统中研究较多。PARK等[42]报告, 用乙烯醋酸乙烯共聚物 (ethylene vinyl acetate copolymer,EVAc ) 制备的 bFGF 缓释微球, 在促进鸡视网膜再生中疗效显著。胡隽宇等[43]将制备的 bFGF 缓释微球注射入兔膝关节腔, 观察微球在腔内的降解速率和药物释放情况。发现对照组在 4 d 后关节液内就检测不到 bFGF 了,而微球组 bFGF 在腔内能稳定释放超过 10 d。
各项实验表明,bFGF 缓释微球能有效延缓 bFGF释放,延长药物体内作用时间。而且具有制备工艺简便、生物相容性能良好等优点[44],显示出较为广阔的应用前景。目前关于 aFGF微球的研究甚少,aFGF与bFGF具有高度同源性,aFGF 缓释微球的研究值得进一步开展。
微球作为缓释药物载体的研究可谓层出不穷,但微球包载药物也存在一定的缺陷。为更好用于临床, 还应进一步深入研究微球在体内不同组织局部的降解和释药动力学规律,以不断优化微球的制备工艺[45]。微球在体内的降解易受多种内外环境因素的影响,这一点值得关注。
纤维蛋白胶 (fibrin glue)是一种低抗原生物蛋白制剂,有着良好的生物相容性、降解性和可塑性[46]。借助其三维网状结构,多种细胞能更加顺利地迁移至创伤部位,更好地介导细胞信号传导,促进细胞粘附和增殖,修复缺损组织[47]。利用纤维蛋白胶包载生长因子,可保护其内部的生长因子不被水解,而且能使之随纤维蛋白胶的降解逐渐释放,是作为生长因子类药物缓释载体的不错选择[48]。
ISHII 等[49]将 bFGF 与纤维蛋白胶混合,发现使原本生物半衰期为 24 h的 bFGF生物活性持续达5 d,对兔关节软骨损伤修复作用明显。研究说明以纤维蛋白胶为载体能有效使 bFGF 缓慢释放,防止药物局部过快流失。这为生长因子临床缓释制剂的研发提供了新的思路。同时,随着纤维蛋白胶提取工艺的逐渐成熟,其临床应用随之扩大,因此研制纤维蛋白胶包载的生长因子制剂具有潜在应用价值。
aFGF 被广泛应用于临床创伤修复、神经和血管再生。然而,近年来研究发现,在多种恶性肿瘤中均存在FGFs及其FGFR过度表达现象,这可能表明其与肿瘤细胞增殖有潜在联系。一项评估 aFGF 对宫颈癌细胞增殖影响的研究显示,aFGF 在宫颈癌组织中呈现高表达状态,其水平与临床分期呈正相关 [50]。
虽然数十年的临床跟踪观察并没有发现任何致癌效应,但 aFGF 类药物是否潜在促进恶性肿瘤增殖的作用还有待更长期的探索。同时,临床在使用该类药物时,应注意相关药物不良反应的监测评估。
目前包载 aFGF 用于临床的载体材料十分有限。临床应用较多的主要是凝胶制剂和胶原海绵,但也各有其不足之处。
凝胶制剂常用材料如胶原、海藻酸、聚乙醇酸等[51],具有价格实惠、机械力度强等优点。但研究发现其降解产物具有细胞毒性作用,并能引起机体的免疫反应,这一定程度限制了临床制剂使用。同时在临床应用中发现,凝胶制剂注射给药后,容易出现机体一过性血脂升高,在体内不能被生物降解排出等问题。
脂质体具有热不稳定性,这大大制约了其长期使用,增加了操作研究的复杂性。此外,脂质体药物系统的产业化与经济性仍是其发展瓶颈。主要是因为脂质体药物的质量控制体系较为繁琐,而注射用高纯度的膜材料价格昂贵,这是脂质体药物开展广泛临床应用的首要问题[52]。
除此之外,目前大多数 aFGF 包载材料的研究仍处于初步阶段,尚未开展深入的临床研究。如纳米银敷料和生物敷料A等,在已报道的临床研究中效果良好,但要真正开展大范围使用,还有待更进一步的研究。同时,研制的新型载体制剂的制备工艺、稳定性、安全性等还需不断研究完善。因此,通过载体材料包载的 aFGF 产品尚未真正步入临床进行广泛应用,要获得能在临床中推广使用、性能良好、经济实惠、使用方便的 aFGF药物还需投入更多的后续研究。相信随着今后研究的不断深入和 aFGF 包载材料生产工艺的进一步发展,现存的问题会得到有效解决。
The authors have declared that no competing interests exist.
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Acidic fibroblast growth factor (aFGF) is a neurotrophic factor which is a powerful neuroprotective and neuroregenerative factor of the nervous system. Prior study had shown that levels of FGFs significantly increase following ischemic injury, reflecting a physiological protection mechanism. However, few reports demonstrated the efficacy of applying aFGF in cerebral ischemia. A recent report showed that the intranasal aFGF treatment improved neurological functional recovery; however, it did not significantly reduce the lesion size in ischemic rats. The present study examines the neuroprotective effect of aFGF on cortical neuron-glial cultures under oxygen glucose deprivation (OGD)-induced cell damage and investigates whether epidural application of slow-released aFGF could improve benefit on ischemic stroke injury in conscious rats. We used a topical application of aFGF mixed in fibrin glue, a slow-release carrier, over the peri-ischemic cortex and examined such treatment on cerebral infarction and behavioral impairments of rats subjected to focal cerebral ischemia (FCI). Results demonstrate that aFGF effectively protected cortical neuron-glial cultures from OGD-induced neuronal damage. Neurite extension from cortical neurons was significantly enhanced by aFGF, mediated through activation of AKT and ERK. In addition, topical application of fibrin glue-mixed aFGF dose-dependently reduced ischemia-induced brain infarction and improved functional restoration in ischemic stroke rats. Slow-released aFGF not only protected hippocampal and cortical cell loss but reduced microglial infiltration in FCI rats. Our results suggest that aFGF mixed in fibrin glue could prolong the protective/regenerative efficacy of aFGF to the damaged brain tissue and thus improve the functional restorative effect of aFGF.
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Abstract Acidic fibroblast growth factor (aFGF) exerts a protective effect on spinal cord injury (SCI) but is limited by the lack of physicochemical stability andthe ability to cross the blood spinal cord barrier (BSCB). As promising biomaterials, hydrogels contain substantial amounts of water and a 3D porous structureand are commonly used to load and deliver growth factors. Heparin can not only enhance growth factor loading onto hydrogels but also can stabilize the structure and control the release behavior. Herein, a novel aFGF-loaded thermosensitive heparin-poloxamer (aFGF-HP) hydrogel was developed and applied to provide protection and regeneration after SCI. To assess the effects of the aFGF-HP hydrogel, BSCB restoration, neuron and axonal rehabilitation, glial scar inhibition, inflammatory response suppression and motor recovery were studied both in vivo and in vitro. The aFGF-HP hydrogels exhibited sustained release of aFGF and protected the bioactivity of aFGF in vitro. Compared to groups i.v. administered either drug-free HP hydrogel or aFGF alone, the aFGF-HP hydrogel group revealed prominent and attenuated disruption of the BSCB, reduced neuronal apoptosis, reactive astrogliosis and increased neuron and axonal rehabilitation both in vivo and in vitro. This work provides an effective approach to enhance recovery after SCI and provide a successful strategy for SCI protection.
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Wound healing is a dynamic process that relies on coordinated signaling molecules to succeed. Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is proven to accelerate healing, however precise control over its application is necessary to reduce side effects and achieve desired therapeutic benefit. To achieve effective growth factor delivery we designed a bioactive heparin-based coacervate. In vitro, HB-EGF released from the coacervate delivery system displayed enhanced bioactivity and promoted human keratinocyte migration while preserving cell proliferative capability. In a mouse excisional full-thickness wound model, controlled release of HB-EGF within the wound significantly accelerated wound closure more effectively than an equal dosage of free HB-EGF. Healing was induced by rapid re-epithelialization, granulation tissue formation, and accompanied by angiogenesis. Consistent with in vitro results, wounds treated with HB-EGF coacervate exhibited enhanced migration of keratinocytes with retained proliferative potential, forming a confluent layer for regained barrier function within 7 days. Collectively, these results suggest that coacervate-based controlled release of HB-EGF may serve as a new therapy to accelerate healing of cutaneous wounds. (C) 2012 Elsevier B.V. All rights reserved.
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DOI:10.1021/bi9521755
URL
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篇首： 在我们治疗过程中,常常会遇到各种难治的创面,无论是深度烧烫伤造成的不愈创面,还是感染导致的溃疡创面,长期卧床导致的褥疮,都是目前每个医生都头痛的问题,往往得通过手术治疗来解决.
[本文引用:1]
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1974年，Gospodarowicz等从牛脑垂体中分离纯化出一种对成纤维细胞系Balb/c3T3的分裂增生具有促进效应的多肽，命名为成纤维细胞生长因子，其等电点为9．16。后来发现脑组织中尚有另外一种与其同源性较强、功能相似但等电点为5．16的FGF，
[本文引用:1]
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| [8] |
This study aims to investigate the preclinical performance and mechanism of a novel strategy of aFGF-loaded heparin-modified microbubbles (aFGF-HMB) combined with ultrasound-targeted microbubble...
[本文引用:1]
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| [9] |
The loss of lower urinary tract (LUT) control is a ubiquitous consequence of a complete spinal cord injury, attributed to a lack of regeneration of supraspinal pathways controlling the bladder. Previous work in our lab has utilized a combinatorial therapy of peripheral nerve autografts (PNG), acidic fibroblast growth factor (aFGF), and chondroitinase ABC (ChABC) to treat a complete T8 spinal cord transection in the adult rat, resulting in supraspinal control of bladder function. In the present study we extended these findings by examining the use of the combinatorial PNG+aFGF+ChABC treatment in a T8 transected mouse model, which more closely models human urinary deficits following spinal cord injury. Cystometry analysis and external urethral sphincter electromyograms reveal that treatment with PNG+aFGF+ChABC reduced bladder weight, improved bladder and external urethral sphincter histology, and significantly enhanced LUT function, resulting in more efficient voiding. Treated mice's injured spinal cord also showed a reduction in collagen scaring, and regeneration of serotonergic and tyrosine hydroxylase-positive axons across the lesion and into the distal spinal cord. Regeneration of serotonin axons correlated with LUT recovery. These results suggest that our mouse model of LUT dysfunction recapitulates the results found in the rat model and may be used to further investigate genetic contributions to regeneration failure.
[本文引用:1]
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| [10] |
to investigate the ability of drug-loaded N,O-carboxymethyl chitosan (CMCS) hydrogels to modulate wound healing after glaucoma filtration surgery.the drug-loaded CMCS hydrogels were in situ synthesized using genipin as the crosslinker in the presence of 5-fluorouracil (5FU) or bevacizumab. Their structures were characterized by FTIR, ultraviolet-visible (UV-vis) spectroscopy and scanning electron microscopy (SEM). In-vitro drug release experiments and in vivo evaluation in rabbits were performed.the results of FTIR, UV-vis spectroscopy and SEM analyses indicated that 5FU was encapsulated into the CMCS hydrogels that were crosslinked by genipin. The in vitro drug release experiments showed that nearly 100% of 5FU was released from the drug-loaded hydrogels within 8 h, but less than 20% bevacizumab was released after 53 h. The in vivo evaluation in rabbits indicated that the drug-loaded CMCS hydrogels were nontoxic to the cornea and were gradually biodegraded in the eyes. Furthermore, the drug-loaded CMCS hydrogels effectively inhibited conjunctival scarring after glaucoma filtration surgery and controlled postoperative intraocular pressure (IOP).the drug-loaded CMCS hydrogels provide a great opportunity to increase the therapeutic efficacy of glaucoma filtration surgery.
[本文引用:1]
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| [11] |
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Abstract Hydrogels are considered key tools for the design of biomaterials, such as wound dressings, drug reservoirs, and temporary scaffolds for cells. Despite their potential, conventional hydrogels have limited applicability under wet physiological conditions because they suffer from the uncontrollable temporal change in shape: swelling takes place immediately after the installation. Swollen hydrogels easily fail under mechanical stress. The morphological change may cause not only the slippage from the installation site but also local nerve compression. The design of hydrogels that can retain their original shape and mechanical properties in an aqueous environment is, therefore, of great importance. On the one hand, the controlled degradation of used hydrogels has to be realized in some biomedical applications. This Progress Report provides a brief overview of the recent progress in the development of hydrogels for biomedical applications. Practical approaches to control the swelling properties of hydrogels are discussed. The designs of hydrogels with controlled degradation properties as well as the theoretical models to predict the degradation behavior are also introduced. Moreover, current challenges and limitation toward biomedical applications are discussed, and future directions are offered. 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[本文引用:1]
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Wound therapy remains a clinical challenge. Incorporation of growth factors (GFs) into heparin-functionalized polymer hydrogel is considered as a promising strategy to improve wound healing efficiency. However, different GFs incorporation into the same heparin-based hydrogels often lead to different wound healing effects, and the underlying GF-induced wound healing mechanisms still remain elusive. Herein, we developed a thermos-sensitive heparin-poloxamer (HP) hydrogel to load and deliver different GFs (aFGF and bFGF) for wound healing in vivo. The resulting GFs-based hydrogels with and without HP hydrogels were systematically evaluated and compared for their wound healing efficiency by extensive in vivo tests, including wound closure rate, granulation formation, re-epithelization, cell proliferation, collagen, and angiogenesis expressions. While all GFs-based dressings with and without HP hydrogels exhibited better wound healing efficacy than controls, both HP-aFGF and HP-bFGF hydrogels demonstrated thei...
[本文引用:1]
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| [15] |
Peptide RADA can undergo spontaneous assembly into well ordered nanofibers and hydrogels in its water solution.In this work,a variety of proteins,including IGF-1,aFGF and VEGF with different molecular weight and isoelectric points,were chosen and encapsulated within the RADA peptide hydrogel.UV-vis spectroscopy was used to determine the concentration of the released proteins in the solution.The release kinetics suggested that protein diffusion through nanofiber hydrogels depended primarily on the size of the protein and the density of the peptide nanofiber.Circular dichroism(CD) spectroscopy indicated that the encapsulation and release by RADA hydrogel did not affect the secondary structure of the proteins studied.
[本文引用:2]
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| [16] |
While silk-based microfibrous scaffolds possess excellent mechanical properties and have been used for ligament tissue-engineering applications, the microenvironment in these scaffolds is not biomimetic. We hypothesized that coating a hybrid silk scaffold with an extracellular matrix (ECM)-like network of self-assembling peptide nanofibers would provide a biomimetic three-dimensional nanofibrous microenvironment and enhance ligament tissue regeneration after bone marrow-derived mesenchymal stem cell (BMSC)-seeding. A novel scaffold possessing a triple structural hierarchy comprising macrofibrous knitted silk fibers, a silk microsponge, and a peptide nanofiber mesh was developed by coating self-assembled RADA16 peptide nanofibers on a silk microfiber-reinforced-sponge scaffold. Compared with the uncoated control, RADA-coated scaffolds showed enhanced BMSC proliferation, metabolism, and fibroblastic differentiation during the 3 weeks of culture. BMSC-seeded RADA-coated scaffolds showed an increasing temporal expression of key fibroblastic ECM proteins (collagen type I and III, tenascin-C), with a significantly higher tenascin-C expression compared with the controls. BMSC-seeded RADA-coated scaffolds also showed a temporal increase in total collagen and glycosaminoglycan production (the amount produced being higher than in control scaffolds) during 3 weeks of culture, and possessed 7% higher maximum tensile load compared with the BMSC-seeded control scaffolds. The results indicate that the BMSC-seeded RADA-coated hybrid silk scaffold system has the potential for use in ligament tissue-engineering applications. 2012 Mary Ann Liebert, Inc.
[本文引用:1]
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Abstract Biomedical researchers have become increasingly aware of the limitations of conventional 2-dimensional tissue cell culture systems, including coated Petri dishes, multi-well plates and slides, to fully address many critical issues in cell biology, cancer biology and neurobiology, such as the 3-D microenvironment, 3-D gradient diffusion, 3-D cell migration and 3-D cell-cell contact interactions. In order to fully understand how cells behave in the 3-D body, it is important to develop a well-controlled 3-D cell culture system where every single ingredient is known. Here we report the development of a 3-D cell culture system using a designer peptide nanofiber scaffold with mouse adult neural stem cells. We attached several functional motifs, including cell adhesion, differentiation and bone marrow homing motifs, to a self-assembling peptide RADA16 (Ac-RADARADARADARADA-COHN2). These functionalized peptides undergo self-assembly into a nanofiber structure similar to Matrigel. During cell culture, the cells were fully embedded in the 3-D environment of the scaffold. Two of the peptide scaffolds containing bone marrow homing motifs significantly enhanced the neural cell survival without extra soluble growth and neurotrophic factors to the routine cell culture media. In these designer scaffolds, the cell populations with beta-Tubulin(+), GFAP(+) and Nestin(+) markers are similar to those found in cell populations cultured on Matrigel. The gene expression profiling array experiments showed selective gene expression, possibly involved in neural stem cell adhesion and differentiation. Because the synthetic peptides are intrinsically pure and a number of desired function cellular motifs are easy to incorporate, these designer peptide nanofiber scaffolds provide a promising controlled 3-D culture system for diverse tissue cells, and are useful as well for general molecular and cell biology.
[本文引用:1]
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Objective: To investigate therapeutic effects of self-assembling peptide RADA16-I nanofiber scaffold. Methods: Performed a deep demal partial thickness burn model at the dorsal skin of female Sprague-dawley rats with an electrical scald machine. On the 7th, 10th, 14th day after injury, the wound specimens were removed for immunohistochemical evaluation. Digital photomicrographs of the FGF and EGF-positive tissue were taken and transformed into image analysis software to estimate the intensity of EGF and FGF protein expression with integral optical density. Results: Immunohistochemistry showed the bFGF and EGF were obviously expressed in nascent tissue such as epidermis and glands when wounds were treated with the RADA16-I after injury, compared the blank control group ,the difference was statistically significant (P0.05). Conclusion: There is promoting effect of self-assembling peptide to burn skin growth factor expression.
[本文引用:1]
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| [19] |
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| [20] |
药用辅料和药物活性成分共同组成了我们日常使用的药品,药用辅料同药物活性成分一样全程参与了体内的吸收、分布、代谢、排泄过程,所以药用辅料的安全性直接影响到了药物制剂的安全性,本文从药用辅料本身的毒副作用、药用辅料同药物活性物质(API)的配伍禁忌、药用辅料有毒副作用的杂质以及其他引起的药品安全性问题的辅料因素等四个方面阐述了药用辅料同药品安全性的关系。
[本文引用:1]
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| [21] |
Multidrug resistance and cancer metastases are two obstacles to a successful chemotherapy and metastases are closely associated with drug resistance. Mitochondrial targeting topotecan-loaded liposomes have been developed to overcome this resistance and resistance-related metastases. Investigations were performed on breast cancer MCF-7 and resistant MCF-7/adr cells, MCF-7 and resistant MCF-7/adr tumor spheroids, resistant MCF-7/adr cell xenografts in nude mice, and a naturally resistant B16 melanoma metastatic model in nude mice. The mitochondrial targeting topotecan-loaded liposomes were approximately 64 nm in size, and exhibited the strongest inhibitory effects on MCF-7 cells and resistant MCF-7/adr cells. Mitochondrial targeting effects were demonstrated by co-localization in mitochondria, enhanced drug content in mitochondria, dissipated mitochondrial membrane potential, opening of mitochondrial permeability transition pores, release of cytochrome C, and activation of caspase 9 and 3. The targeting liposomes had a stronger inhibitory effect on the resistant tumor spheroids in vitro, enhanced accumulation in resistant MCF-7/adr cell xenografts in mice, as well as being very effective on resistant MCF-7/adr cell xenografts in mice, and having a marked anti-metastastic effect on the naturally resistant B16 melanoma metastatic model in mice. In conclusion, mitochondrial targeting topotecan-loaded liposomes could be a promising strategy for treating resistant cancers and resistance-related metastases.
[本文引用:1]
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Even when faced with elimination, functional materials may offer new alternatives to expensive drugs. Once used to treat benign prostate hypertrophy, the US Food and Drug Administration (FDA) suspended the use of lonidamine due to the occurrence of liver problems arising from its poor pharmaceutical properties. The objectives of the present study were to develop targeting lonidamine liposomes in combination with targeting epirubicin liposomes to circumvent drug-resistant cancer. Evaluations were performed on A549 and drug-resistant A549cDDP lung cancer cells and drug-resistant A549cDDP xenografted BALB/c nude mice. A DQA-PEG(2000)-DSPE conjugate was incorporated onto the liposomes as a targeting molecule. The constructed targeting lonidamine liposomes and targeting epirubicin liposomes measured were approximately 80 nm. The targeting lonidamine liposomes significantly enhanced the inhibitory effect of the targeting epirubicin liposomes in the drug-resistant A549cDDP cells in a lonidamine dose-dependent manner. Mechanism studies revealed that the targeting liposomes were selectively accumulated in the mitochondria, dissipating the mitochondrial membrane potential, opening the mitochondrial permeability transition pores, and releasing cytochrome C by translocation. This initiated a cascade of caspase 9 and 3 reactions and activated the pro-apoptotic Bax protein while suppressing the anti-apoptotic Mcl-1 protein, thereby enhancing the cytotoxic effect by acting on the mitochondrial signaling pathways. The efficacy in treating the drug-resistant A549cDDP xenografted tumor model after administration of the targeting lonidamine liposomes plus targeting epirubicin liposomes was the most significant compared with the administration of the controls at comparable doses. In conclusion, targeting lonidamine liposomes could be used as a potent co-therapy with an anticancer agent to enhance the efficacy of treating drug-resistant cancer by acting on the mitochondrial signaling pathways. (C) 2013 Elsevier Ltd. All rights reserved.
[本文引用:1]
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| [23] |
采用pH梯度法制备酸性成纤维细胞生长因子（aFGF）脂质体，以包封率为考察指标，单因素筛选最优制备工艺：十八胺用量为0.02 g，柠檬酸缓冲液浓度为0.03 mol/L，aFGF投药量为0.04 mg/mL，内外水相pH差（ΔpH）为3.5，孵育温度为35 ℃，孵育时间为15 min。aFGF脂质体包封率为(78.82±2.56)%，Zeta电位为 9.68 mV，平均粒径 124.03 nm。透析法测定aFGF脂质体的体外释药动力学，研究结果表明aFGF脂质体与 aFGF原液相比具有一定的缓释作用。稳定性研究表明，aFGF脂质体较aFGF原液稳定性得到提高，4 ℃贮存为佳。所制备的aFGF脂质体包封率较高，稳定性较好，具有一定的缓释作用。
[本文引用:1]
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| [25] |
目的探讨胶原蛋白海绵在腰椎间盘突出症手术中的止血作用。方法选择在本院脊柱外科收治的椎间盘突出症单纯行半椎板减压髓核摘除的患者,随机分为两组,一组用胶原蛋白海绵覆盖在硬脊膜外后缝合切口,另一组不用胶原蛋白海绵,直接缝合切口,记录患者术后24、48h内引流血量,根据手术前、后血红蛋白检测结果计算患者血红蛋白的丢失量,并对两组数据进行比较。结果应用胶原蛋白海绵组引流量较不用组引流量少,二者间具有显著性差异。结论在腰椎半椎板减压髓核摘除术后应用胶原蛋白海绵可以明显减少椎管内出血,临床值得推荐。
[本文引用:1]
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| [26] |
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| [27] |
目的:探讨新型的创伤敷料用于局部治疗压疮.方法:制备高纯度的Ⅰ型胶原蛋白溶液,加入酸性成纤维细胞生长因子溶液,冷冻干燥成为海绵体,再进行生物学性能检测,包括急性毒性试验、刺激性试验、过敏性试验、溶血性试验、细胞毒试验.1998-04/2003-06广州市红十字会医院的压疮患者55例.按<护理学基础>压疮评定标准确定其面积、深度,选择性质基本相同的创面分为两组:治疗组用酸性成纤维细胞生长因子胶原海绵,对照组用油纱.结果:所制备的酸性成纤维细胞生长因子胶原海绵为白色的纤维状海绵体,电镜下可见多孔网状结构,酸性成纤维细胞生长因子胶原海绵体的毒理学试验结果均呈阴性;治疗组Ⅱ,Ⅲ期压疮好转率均为100%.对照组Ⅱ期压疮好转率达50%,Ⅲ期压疮好转率为0.结论:酸性成纤维细胞生长因子胶原海绵无毒副作用.
[本文引用:2]
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背景:胶原蛋白海绵具有良好的功能和特性,及其易于加工、灭菌和保存等独特的优势,被视为最有用途的生物材料,具有广泛的科研和临床应用价值.目的:介绍胶原蛋白海绵的性质,对近年来胶原蛋白海绵在临床应用上的研究成果进行综述.方法:由第一作者应用计算机检索2000-01/ 2010-08 Pubmed数据库和Elsevier数据库,在标题和摘要中以 "collagen,collagen sponge,clinical application"为检索词进行检索.检索1993-01/2010-08 CNKI数据库,在标题和摘要中以"胶原,胶原蛋白海绵,临床应用"为检索词进行检索.纳入38篇文献进行综合分析.结果与结论:胶原蛋白海绵作为一种新型生物材料,越来越广泛地被应用于止血、创面愈合、抗感染、软骨修复、神经修复等相关方面的组织工程与临床研究.但目前所使用的胶原几乎都是来源于动物,无法彻底消除免疫原性.国外已有人利用生物反应器和转基因技术合成了重组人胶原,其在临床应用上的有效性和安全性等问题仍有待进一步的探索和研究.<dt><strong><t>Abstract：</t></strong></dt><dd>BACKGROUND: Collagen sponge is considered the most useful biomaterial owing to its excellent function and properties, easy processing, sterilization, and preservation and has been widely used in scientific research and clinical application. OBJECTIVE: To describe the properties of collagen sponge and to review the research progress of collagen sponge in clinical application in recent years. METHODS: A computer-based retrieval was performed by the first author to search for manuscripts published from January 2000 to August 2010 in Pubmeds and Elsevier databases and for manuscripts published from January 1993 to August 2010 in CNKI database using key words "collagen, collagen sponge, clinical application" in title and abstract items in English and Chinese language, respectively. RESULTS AND CONCLUSION: Collagen sponge, as a new biological material, has been widely applied in tissue engineering research in terms of hemostasis, wound healing, anti-infection, cartilage repair, and nerve repair. But at present, nearly all collagen is from animals and immunogenicity cannot be thoroughly eliminated. Researchers outside of China have synthesized recombinant human collagen using bioreactor and transgenic technology, but its efficacy and safety in clinical application needs further investigation and research.
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目的探讨猪脚肌腱提取的Ι型胶原与壳聚糖混合,交联冻干后形成的复合Ι型胶原海绵对创伤创面出血的止血效果.方法用新西兰大白兔作实验动物,对其皮下出血、体表浅动静脉断裂损伤、肝损伤进行止血试验,同时与明胶海绵、纱布等止血效果作比较,观察其止血时间、敷料与创面的粘合等情况,并定期观察创面愈合和体内吸收情况.结果本试验表明:复合Ι型胶原海绵的止血时间约2分钟,明胶海绵为3.5分钟,纱布压敷为10分钟以上;复合Ι型胶原海绵和明胶海绵均能在体内降解吸收.结论复合Ι型胶原海绵止血效果最好,无论是止血时间、止血效果、与伤口的粘附能力都优于其他2种材料,并能在体内降解吸收,因此,是一种较理想的创伤止血材料.
[本文引用:1]
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| [30] |
目的：探讨纳米银敷料结合重组牛碱性成纤维细胞生长因子凝胶治疗烧伤残余创面的临床效果。方法选取我院自2011年10月-2013年10月收治的76例出现烧伤残余创面患者随机分为观察组与参考组，各为38例，观察组患者采用纳米银敷料结合重组牛碱性成纤维细胞生长因子凝胶治疗，参考组患者采用无菌石蜡油纱布联合生理盐水换药，比较两组患者创面愈合时间、感染例数、治疗7d时创面细菌培养情况及药物不良反应。结果参考组患者创面愈合时间明细小于观察组（P〈0.05）；参考组患者出现13例感染，感染率为34.2%，观察组患者出现3例感染，感染率为7.9%，数据比较有统计学意义（P〈0.05）；参考组患者7 d时创面细菌检出率明显高于观察组（P〈0.05）；两组患者药物不良反应比较无统计学意义（P〉0.05）。结论采用纳米银敷料结合重组牛碱性成纤维细胞生长因子凝胶治疗烧伤残余创面，抗菌作用显著，能够促进创面修复，值得推广使用。
[本文引用:1]
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| [31] |
目的:探讨重组人酸性成纤维细胞生长因子 (recombinant human acidic fibroblast growth factor～rh-aFGF)与纳米银敷料联合应用治疗深Ⅱ度烧伤创面的疗效.方法:深Ⅱ度烧伤创面患者98例,随机采用自身对照选择相同深度的两个创 面分为应用重组人酸性成纤维细胞生长因子(rh-aFGF)与纳米银敷料联合应用治疗组(简称治疗组);应用重组人酸性成纤维细胞生长因子(rh- aFGF)与凡士林纱布治疗(简称对照组).结果:与对照组比较,治疗组创面愈合时间明显缩短.差异有统计学意义(P＜0.05),抑(杀)菌效果显著. 结论:重组人酸性成纤维细胞生长因子(rh-aFGF)与纳米银敷料联合应用治疗深Ⅱ度烧伤创面能明显促进深Ⅱ度创面愈合,有效抑制或杀灭烧伤创面病原 菌,明显缩短深Ⅱ度烧伤创面愈合时间.
[本文引用:1]
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| [32] |
目的探索外用重组牛碱性成纤维细胞生长因子（bFGF）治疗深度烧伤创面的最佳用药浓度、给药方法与剂量,以指导临床应用。方法设等渗盐水加甲硝唑治疗为对照组,选择bFGF的不同用药浓度（75Au/cm^2,150Au/cm^2,300Au/cm^2）每种浓度选择3种用药方法（每日1次法,每日2次法,每日3次法）进行创面愈合的比较性研究。结果bFGF在一定浓度范围内（75～300Au/cm^2）可有效促进创面愈合（P〈0.05）,用药之间方法比较,差异有统计学意义（P〈0.01）。每日2次法能明显缩短愈合时间。结论用药的次数与方法对创面愈合的影响比用药的浓度更为重要,从方便、合理与经济的角度考虑,每日用药2次值得临床上推荐。
[本文引用:1]
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背景:在临床治疗面部Ⅱ度烧伤中,生物敷料A及银离子水胶体油纱 在吸收渗液、黏附性、抗菌等方面都具有不错的表现.目的:观察面部Ⅱ度烧伤早期清创后生物敷料A对比银离子水胶体油纱覆盖的临床疗效.方法:纳入15例浅 Ⅱ度及10例深Ⅱ度面部烧伤患者,将同一患者相同烧伤深度及同等大小的对称创面分两侧治疗,实验侧清创后采用生物敷料A覆盖创面,对照侧清创后采用银离子 水胶体油纱覆盖创面,对比两侧创面愈合时间、创面感染情况、换药次数、创面愈合后皮肤质量情况、换药舒适度及敷料覆盖舒适度.结果与结论:在浅Ⅱ度烧伤患 者中,实验侧换药次数及敷料覆盖舒适度优于对照侧(P < 0.05),换药舒适度差于对照侧(P < 0.05),两侧创面愈合时间、创面感染及愈合后皮肤质量情况无差异.在深Ⅱ度烧伤患者中,实验侧创面愈合时间、换药次数、愈合后皮肤质量情况、换药舒适 度及敷料覆盖舒适度优于对照侧(P < 0.05),换药舒适度差于对照侧(P < 0.05),两侧创面感染情况无差异.表明生物敷料A与银离子水胶体油纱修复面部浅Ⅱ度烧伤创面的疗效相似,但生物敷料A修复深Ⅱ度烧伤创面更有利于促进 创面愈合,提高创面愈合质量.
[本文引用:1]
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Wound management covers all aspects of patient care from initial injury, treatment of infection, fluid loss, tissue regeneration, wound closure to final scar formation and remodeling. There are many wound-care products available including simple protective layers, hydrogels, metal ion-impregnated dressings and artificial skin substitutes, which facilitate surface closure. This review examines recent developments in wound dressings, biomaterials and devices. Particular attention is focused on the design and manufacture of hydrogel-based dressings, their polymeric constituents and chemical modification. Finally, topical negative pressure and hyperbaric oxygen therapy are considered. Current wound-management strategies can be expensive, time consuming and labor intensive. Progress in the multidisciplinary arena of wound care will address these issues and be of immense benefit to patients, by improving both clinical outcomes and their quality of life.
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Abstract Debridement is integral to wound bed preparation by removing devitalised tissue, foreign material, senescent cells, phenotypically abnormal/dysfunctional cells (cellular burden) and bacteria sequestrum (biofilm). While the body of evidence to substantiate the benefits of debridement is growing, little is known about the cost-effectiveness of each debridement method. The purpose of this analysis was to compare cost-effectiveness of various debridement methods and clinical outcomes to help inform clinicians and policy makers of the cost-effectiveness associated with the various types of therapies and the impact they can have on the Canadian health care system. Results indicated that sharp debridement was the most cost-effective followed by enzymatic debridement method.
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Abstract AIMS AND OBJECTIVES: To describe the self-reported wound care practices of acute care nurses practising in a large metropolitan hospital in Queensland, Australia. BACKGROUND: Wound infections occur in up to 30% of surgical procedures and are the third most commonly reported hospital-acquired infection. The growing complexity and cost of wound care demand that nurses use wound care knowledge based on best practice guidelines. DESIGN: Descriptive cross-sectional survey design. METHODS: A convenience sample of 250 medical and surgical nurses working in an acute care facility was invited to complete a 42-item survey. The survey was based on an extensive literature review and an environmental scan of wound care issues in major hospitals, Australia. RESULTS: The survey was completed by 120 acute care nurses with a response rate of 48%. Ninety (75·6%) respondents reported that 'wound appearance' was the most important factor guiding their choice of dressing product. Only 6 (5·0%) respondents considered the cost of a dressing product 'highly important'. Fifty-nine (50·4%) respondents reported being 'unaware' of the national standards pertaining to wound management, and only 41 (34·7%) respondents reported that their knowledge of wound products was 'good' or 'excellent'. The majority (n02=0289, 75·4%) of respondents used the hospital's wound care specialist nurses as the primary source of information in regard to managing acute wounds. CONCLUSIONS: Although acute care nurses have a sound knowledge of wound healing processes, it appears that many do not use the recommended clinical guideline pertaining to wound care. RELEVANCE TO CLINICAL PRACTICE: While it is important for nurses to detect early wound complications, treatment plans based on wound assessments need to be informed by current clinical guidelines. In implementing the guideline, it is essential to first identify barriers and facilitators to knowledge transfer. 08 2013 John Wiley & Sons Ltd.
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AimsTo evaluate the antibacterial efficacy of silicate bioactive glass nanoparticles/collagen composites functionalized with tetracycline hydrochloride (TCH).Methods and ResultsDifferent concentrations of tetracycline hydrochloride (TCH) were incorporated on silicate bioactive glass nanoparticles/collagen composites by dipping these biomaterials for 48 h at 37°C in a solution of simulated body fluid (SBF) plus 0·05, 0·20 or 0·35 mg ml611 of the antibiotic. TCH release was assessed in double-distilled water at 37°C up to 72 h. The antibacterial activity of the samples has been evaluated in two ways: inhibition zone test and plate count method. The experiments were performed in vitro up to 48 h on four staphylococci strains (Staphylococcus aureus ATCC29213, ATCC25923, ATCC6538P and Staphylococcus epidermidis ATCC12228). The new composites were also tested for cytotoxicity on MG-63 human osteosarcoma cells. The results showed that the incorporation and release of TCH was dependent on the initial concentration of TCH in SBF. The biomaterials also inhibited the Staph. aureus cell growth even though the efficacy was similar for all concentration. On the other hand, no cytotoxic effects were found on osteoblast-like cells, even at the highest concentration.ConclusionsConsidering all results, it can be concluded that the new composite acts as a suitable bioactive carrier of TCH and could have potential in the prevention of biomaterial related infections.Significance and Impact of the StudyThe results suggest a potential application as wound dressing.
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目的探讨应用生物敷料A联合酸性成纤维细胞生长因子治疗深度烧伤创面的经验。方法选择25例深度烧伤患者,早期给予切、削痂手术后,创面喷洒酸性成纤维细胞生长因子后,应用生物敷料A覆盖切、削痂后创面,待生物敷料A脱落后,如有残留创面,再给予酸性成纤维细胞生长因子外用包扎。结果 25例患者创面均一期愈合,无创面感染的发生。结论生物敷料A具有良好的组织相容性,酸性成纤维细胞生长因子可以刺激细胞增殖,二者结合对深度烧伤创面的治疗具有显著的疗效。
[本文引用:2]
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In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.
[本文引用:1]
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Biodegradable microspheres have gained popularity for delivering a wide variety of molecules via various routes. These types of products have been prepared using various natural and synthetic biodegradable polymers through suitable techniques for desired delivery of various challenging molecules. Selection of biodegradable polymers and technique play a key role in desired drug delivery.This review describes an overview of the fundamental knowledge and status of biodegradable microspheres in effective delivery of various molecules via desired routes with consideration of outlines of various compendial and non-compendial biodegradable polymers, formulation techniques and release mechanism of microspheres, patents and commercial biodegradable microspheres.There are various advantages of using biodegradable polymers including promise of development with different types of molecules. Biocompatibility, low dosage and reduced side effects are some reasons why usage biodegradable microspheres have gained in popularity. Selection of biodegradable polymers and formulation techniques to create microspheres is the biggest challenge in research. In the near future, biodegradable microspheres will become the eco-friendly product for drug delivery of various genes, hormones, proteins and peptides at specific site of body for desired periods of time.
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Abstract We have previously reported that basic fibroblast growth factor (bFGF) can induce retinal regeneration in the stage 22-24 chicken embryo. The present study was undertaken to identify the cellular source of the regenerate and to determine whether other growth factors also elicit regeneration in this animal model. Polymer implants containing bFGF were inserted into eyes of chicken embryos immediately after extirpation of the neural retina. The retinal pigment epithelium (RPE) was left intact. Evaluation by light microscopy revealed that in bFGF-treated eyes the new neural retina arose by transdifferentiation of the entire RPE layer. Differentiation of the new neural retina occurred in a sequence similar to that of normal development but proceeded in a reverse (vitread) direction. All retinal laminae had differentiated by Day 15. However, the regenerate displayed reversed polarity, with photoreceptors closest to the lens. The RPE, pecten, and optic nerve were absent. Focal areas of degeneration in the retinal regenerate became evident for the first time on Day 10. Retinal regeneration was also observed after treatment with higher doses of acidic fibroblast growth factor, but not with nerve growth factor-beta, transforming growth factor-beta 1, insulin, or insulin-like growth factors I or II. These results raise the possibility that FGFs may play a role in retinal differentiation during development.
[本文引用:1]
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背景：聚乳酸-羟基乙酸共聚物包封碱性成纤维细胞生长因子制备的缓释微球在体外磷酸盐缓冲液中能持续释放活性碱性成纤维细胞生长因子。 目的：观察碱性成纤维细胞生长因子微球在兔关节不同功能状态下关节滑液内局部降解、释药动力学规律。 设计、时间及地点：完全随机分组设计的动物实验，于2006—04／2007-03在四川大学建筑与环境学院生物力学工程实验室完成。 材料：81只成年新西兰大白兔。采用复乳法优化处方制备碱性成纤维细胞生长因子-聚乳酸-羟基乙酸共聚物微球。 方法：81只兔按随机数字表法分为4组，微球组（n=36），碱性成纤维细胞生长因子组（n=27），微球组兔双膝关节内注射150mg碱性成纤维细胞生长因子微球（含62．251μg碱性成纤维细胞生长因子）＋0．6mL生理盐水，右膝半屈曲位固定，为微球固定组；左膝不固定，为微球活动组。碱性成纤维细胞生长因子组兔双膝关节内注射62．25μg游离碱性成纤维细胞生长因子＋0．6mL生理盐水，右膝半屈曲位固定，为碱性成纤维细胞生长因子固定组；左膝不固定，为碱性成纤维细胞生长因子活动组。空白对照组9只，兔双膝关节内注射0．6mL生理盐水，不固定。空白微球组9只，兔双膝关节内注射150mg空白聚乳酸-羟基乙酸共聚物微球＋0．6mL生理盐水，不固定。 主要观察指标：于术后1，2，4，6，8，10，12，14，16d采集标本，观察关节液中碱性成纤维细胞生长因子微球形态变化及释药变化，聚乳酸-羟基乙酸共聚物微球载体材料分子质量变化。 结果：微球组在关节液内可持续稳定释放碱性成纤维细胞生长因子10d以上，碱性成纤维细胞生长因子组4d后关节液内未检测到碱性成纤维细胞生长因子。降解14d后，微球活动组球形完全消失，已降解成为一些碎片：微球固定组部分降17
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目的:研究微球中聚乳酸羟基乙酸共聚物(PLGA)浓度与微球结构、释药、降解的关系。方法:以牛血清白蛋白(BSA)为药物,采用复乳法制备PLGA浓度分别为10%、15%、20%的BSA-PLGA微球,以包封率、载药量、粒径为指标考察PLGA浓度对3种微球性质的影响;采用扫描电子显微镜观察3种微球和降解40 d内的外观和内部形态;使用荧光蛋白-异硫氰酸荧光素牛血清白蛋白代替BSA作为模型药物制备PLGA微球,并采用激光共聚焦显微镜观察荧光蛋白在微球骨架内的分布情况;采用BCA法考察3种微球的体外释药情况;采用压汞仪考察降解28 d内20%PLGA所制微球的孔径、孔隙率、截面孔隙率的变化;采用凝胶渗透色谱法检测10%、20%PLGA所制微球降解28 d内分子质量及其降解模型拟合。结果:与10%、15%PLGA所制微球比较,20%PLGA所制微球的包封率[(81.96±1.84)%]和粒径[(139.50±0.21)μm]最大,载药量[(7.28±0.45)%]最低,截面孔隙率[(32.35±1.98)%]和孔径[(12.43±0.14)μm]最小,释药突释率最低,40 d内的释放速率相对较慢,降解后截面孔隙率最大,降解均遵循假一级模式(r2=0.065 3)。结论:在考察范围内,随着PLGA浓度的增加,微球的结构更致密,释药更平稳,降解更易形成中空结构。
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BACKGROUND: Fibrin glue (FG) is a fibrin preparation, which is composed by fibrinogen, thrombin and other biological activity, and it has various functions such as hemostasia, chemotaxis, promoting cell mitosis and other features, besides, it also has good biocompatibility. OBJECTIVE: To review the application of FG in orthopedics. METHODS: The PubMed, Biosis Preview, ScienceDirect, Wanfang and VIP databases were searched by using the keywords of "fibrin glue, biomaterial, application" in English and "fibrin glue, orthopedics, application" in Chinese for relevant articles addressing application of FG in orthopedics published 1995-01/2011-05. Finally, 30 articles were summarized. RESULTS AND CONCLUSION: FG is a kind of multi-bioactive fibrin, which can rapidly form three-dimensional network structure and play a good hemostatic effect. FG can form a local loop at the injection site to play a closed and adhesive effect, and it can be used for preventing postoperative epidural adhesions, inhibiting local inflammation, reducing swelling pressure, and promoting postoperative wound healing. FG can act as a biological matrix used in bone or cartilage tissue engineering.
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Abstract Fibrin polymers are widely used in the tissue engineering field as biomaterials. Although numerous researchers have studied the fabrication of scaffolds using fibrin glue (FG) and bone powder, the effects of varied fibrinogen content during the fabrication of scaffolds on human mesenchymal stem cells (hMSCs) and bone regeneration remain poorly understood. In this study, we formulated scaffolds using demineralized bone powder and various fibrinogen concentrations and analyzed the microstructure and mechanical properties. Cell proliferation, cell viability, and osteoblast differentiation assays were performed. The ability of the scaffold to enhance bone regeneration was evaluated using a rabbit calvarial defect model. Micro-computed tomography (micro-CT) showed that bone powders were uniformly distributed on the scaffolds, and scanning electron microscopy (SEM) showed that the fibrin networks and flattened fibrin layers connected adjacent bone powder particles. When an 800002mg/mL fibrinogen solution was used to formulate scaffolds, the porosity decreased 41.6000200±00023.6%, while the compressive strength increased 1.16000200±00020.020002Mpa, when compared with the values for the 100002mg/mL fibrinogen solution. Proliferation assays and SEM showed that the scaffolds prepared using higher fibrinogen concentrations supported and enhanced cell adhesion and proliferation. In addition, mRNA expression of alkaline phosphatase and osteocalcin in cells grown on the scaffolds increased with increasing fibrinogen concentration. Micro-CT and histological analysis revealed that newly formed bone was stimulated in the scaffold implantation group. Our results demonstrate that optimization of the fibrinogen content of fibrin glue/bone powder scaffolds will be beneficial for bone tissue engineering. Copyright 0008 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
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背景：碱性成纤维细胞生长因子具有促进新生血管生成和结缔组织再生等多种生物学作用，但其在体内可被快速降解，而纤维蛋白胶作为载体则可通过缓释作用避免碱性成纤维细胞生长因子在体内的快速降解，从而更好的发挥其生物学作用，但目前二者的具体运用方式尚处于研究阶段。目的：对碱性成纤维细胞生长因子及纤维蛋白胶在骨科领域的运用研究进展进行综述。方法：由第一作者用计算机检索2000至2014年中国期刊全文数据库和Medline数据库相关文献，总结分析碱性成纤维细胞生长因子及纤维蛋白胶在骨科的运用情况。结果与结论：最终纳入的64篇文献的整理分析结果提示，碱性成纤维细胞生长因子可以通过纤维蛋白胶的载体作用，达到促进促进创伤愈合与组织修复的目的，但多数研究尚处于实验阶段，其在骨科领域的临床应用还需要进一步的探索。
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We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant. Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect. Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans.
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Abstract Fibroblast growth factors (FGFs) play important roles in angiogenesis, wound healing, embryonic development, and endocrine signaling pathways. Increasingly, recent studies have reported aberrant FGF expression in various malignancies. However, the involvement of FGFs in cervical carcinoma pathogenesis remains unclear. We aimed to investigate expression of acidic (aFGF) and basic FGF (bFGF) in patients with this disease, and assess their effects on cervical cancer cell proliferation. Twenty cervical cancer patients and 10 cervical intraepithelial neoplasia (CIN) patients were recruited, and 10 cancer-free individuals were included as controls. Reverse transcription-polymerase chain reaction and western blotting were employed to detect FGF mRNA and protein levels, respectively. Furthermore, HeLa cells were treated with FGFs and subjected to thiazolyl blue tetrazolium bromide assays to quantify proliferation. Compared with CIN and normal cervical tissues, aFGF and bFGF mRNA and protein levels were significantly elevated in cervical carcinomas (P 0.05). HeLa cell proliferation increased in an aFGF- and bFGF-dose-dependent manner (P < 0.05), the latter exerting a more potent proliferative influence, with its effect peaking at 75 ng/mL. aFGF and bFGF were highly expressed in cervical cancer tissues and their levels positively correlated with clinical stage. Both facilitate proliferation of cervical carcinoma cells and are implicated in cancer pathogenesis and progression.
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Tissue engineering promises to be an effective strategy that can overcome the lacuna existing in the current pharmacological and interventional therapies and heart transplantation. Heart failure continues to be a major contributor to the morbidity and mortality across the globe. This may be attributed to the limited regeneration capacity after the adult cardiomyocytes are terminally differentiated or injured. Various strategies involving acellular scaffolds, stem cells, and combinations of stem cells, scaffolds and growth factors have been investigated for effective cardiac tissue regeneration. Recently, injectable hydrogels have emerged as a potential candidate among various categories of biomaterials for cardiac tissue regeneration due to improved patient compliance and facile administration via minimal invasive mode that treats complex infarction. This review discusses in detail on the advances made in the field of injectable materials for cardiac tissue engineering highlighting their merits over their preformed counterparts.
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Abstract The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. Copyright 脗漏 2012 Elsevier B.V. All rights reserved.
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