Microvascular maturity elicited in tissue treated with cytokine-loaded hyaluronan-based hydrogels
Microvascular maturity elicited in tissue treated with cytokine-loaded hyaluronan-based hydrogels
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DOI：
10.1016/j.biomaterials.2008.01.033
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发表时间：
2008-05-01
期刊：
影响因子：
14
通讯作者：
Peattie, Robert A.
中科院分区：
文献类型：
--
作者：
Hosack, Luke W.;Firpo, Matthew A.;Peattie, Robert A.
将由交联的、化学修饰的透明质酸（HA）、明胶（Gtn）和肝素（Hp）组成的水凝胶预先装载血管内皮生长因子（VEGF）、血管生成素-1（Ang-1）、角质形成细胞生长因子（KGF）或血小板衍生生长因子（PDGF），单独或与VEGF组合，并植入Balblc小鼠耳廓中。在术后第7天和第14天，使用免疫组织化学（IHC）染色技术对诱导的血管成熟水平进行定量，并报告为血管成熟指数（VMI）。在两个时间点，发现双重细胞因子组合比单独施用的细胞因子引起更高的成熟水平。例如，含VEGF和KGF的HA：Hp植入物在第7天分别产生-0.1375和-0.092的VMI值，而它们的组合导致VMI为0.176（p < 0.007）。在第7天，7个HA：Hp实验病例中只有一个产生了阳性VMI（VEGF + KGF），而7个HA：Hp病例中有4个在第14天产生了阳性VMI值，表明持续的成熟反应。在用HA：Hp：Gtn实验植入物处理的组织中发现存在相同的一般趋势。在用HA：Hp和含HA的水凝胶处理的组织之间也存在引发成熟度的差异（HA：Hp-VEGF+KGF的VMI=0.176对HA-VEGF + KGF的VMI =-0.064，p < 0.012），并且这些差异被认为是由特征性细胞因子释放速率的差异引起的。该结果还表明，固定化Hp上的多种生长因子（GF）的呈递可积极地促进细胞因子相关的信号转导，这一特性可在未来被利用以提高加载有马槟榔碱的植入物对组织再生治疗策略的功效。(c)2008爱思唯尔有限公司保留所有权利。
Hydrogels composed of crosslinked, chemically modified hyaluronic acid (HA), gelatin (Gtn) and heparin (Hp) were preloaded with vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), keratinocyte growth factor (KGF) or platelet derived growth factor (PDGF) either individually or in combination with VEGF and implanted into the Balblc mouse ear pinna. At 7 and 14 days post-surgery, elicited vascular maturity levels were quantified using immunohistochemical (IHC) staining techniques and reported as a vascular maturity index (VMI). At both time points, it was discovered that the dual cytokine combinations elicited greater maturity levels than that of cytokine administered individually. For example, VEGF and KGF-containing HA:Hp implants at day 7 yielded VMI values of -0.1375 and -0.092, respectively, whereas their combination resulted in a VMI of 0.176 (p < 0.007). At day 7, only one of the seven HA:Hp experimental cases yielded a positive VMI (VEGF + KGF), whereas four of the seven HA:Hp cases yielded positive VMI values at day 14, indicating a sustained maturity response. The same general trends were found to exist in tissue treated with HA:Hp:Gtn experimental implants. Differences in elicited maturity also existed between tissue treated with HA:Hp and HA-containing hydrogels (VMI=0.176 for HA:Hp-VEGF+KGF vs. -0.064 for HA-VEGF + KGF, p < 0.012), and these differences are thought to result from differences in characteristic cytokine release rates. This result also suggests that the presentation of multiple growth factors (GFs) on immobilized Hp may actively contribute to cytokine related signal transduction, a characteristic that may be exploited in the future to improve the efficacy of cytokine-loaded implants towards tissue regeneration therapeutic strategies. (c) 2008 Elsevier Ltd. All rights reserved.