Development of a method for the evaluation of wound tensile strength in cynomolgus macaques
Development of a method for the evaluation of wound tensile strength in cynomolgus macaques
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DOI：
10.1016/j.vascn.2007.08.002
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发表时间：
2008-01-01
影响因子：
1.9
通讯作者：
Martin, Pauline
中科院分区：
文献类型：
--
作者：
Cornacoff, Joel B.;Howk, Kreg;Martin, Pauline
前言：许多体内伤口愈合模型已经被开发出来，以评估药物影响伤口愈合过程的潜力，包括血管生成。这些模型中的大多数经常在啮齿动物、兔子和猪身上进行，并且本质上是终末期的。由于许多正在开发的生物治疗分子的物种特异性，本研究对食蟹猴的非末端模型进行了评估。方法：用微型外科手术刀在正中线两侧各建立3个全厚皮肤切口(2 cm、长3 mm、深3 mm)，以评估创面的抗张强度。伤口用Steristrips(TM)涂在Mastisol(R)上，并用Tegaderm(TM)覆盖。然后给这些动物穿上灵长类夹克。在研究1中，每组3只雄性猕猴每天肌肉注射生理盐水或地塞米松(1 mg/kg)，从第一天到第11天。在研究2中，每组3只雄性猕猴在第一天一次静脉注射生理盐水或抗血管内皮生长因子单抗(20 mg/kg)。在研究1和2中，分别在第1天和第1天制造伤口。在研究3中，每组3只雄性猕猴和3只雌性猕猴分别于第1、8、15和22天注射抗血管内皮生长因子单抗(20 mg/kg)。在研究3中，创面在第12天产生。在创面产生的第4、8和11天，每只动物随机两个切口用生物力学组织定征系统进行评估。结果：在研究1中，与生理盐水阴性对照组相比，地塞米松治疗组在第11天的伤口强度有统计学意义的降低。在研究2中，抗血管内皮生长因子单抗处理的动物在第8天的伤口强度与生理盐水处理的动物相比有统计学意义的降低。对生理盐水处理的动物和抗血管内皮生长因子单抗处理的动物之间的伤口强度的统计评估显示，在第8天，抗血管内皮生长因子单抗治疗组的伤口强度显著降低(图3)。在所有研究中，在评估时都有开放的伤口部位，在第4天从6%到50%，在第8天从3%到17%，在第11天是6%。讨论：这些研究展示了一种潜在的方法来评估食蟹猴无菌伤口的强度，该方法允许在非终末模型中随着时间的推移对动物体内的伤口强度进行多次评估。地塞米松和抗血管内皮生长因子单抗分别在第11天和第8天显著减少创面愈合。目前尚不确定开放切口点的数量是否与测试物品、手术时未完全闭合或灵长类动物外套中的动物移动有关。(C)2007 Elsevier Inc.保留所有权利。
Introduction: Numerous in vivo wound healing models have been developed to evaluate the potential of drugs to affect the processes involved in wound healing, including angiogenesis. The majority of these models are frequently conducted in rodents, rabbits, and pigs and are terminal in nature. Due to the species specificity of many biotherapeutic molecules under development a non-terminal model in the cynomolgus monkey was evaluated in this study. Methods: To evaluate wound tensile strength, 3 full thickness skin incisions (2 cm, long and 3 mm deep) were created on each side of the midline with a micro-fine surgical scalpel. Wounds were closed with SteriStripS(TM) applied over Mastisol(R), and covered with Tegaderm(TM). The animals were then fitted with primate jackets. In Study 1, 3 male macaques per group received daily intramuscular injections of saline or dexamethasone (1 mg/kg) from Day-1 through Day 11. In Study 2, 3 males macaques per treatment group received a single intravenous injection of saline or anti-VEGF mAb (20 mg/kg) on Day-1. In Studies 1 and 2 wounds were created on Day-1. In Study 3, 3 males and 3 female macaques per treatment group received anti-VEGF mAb (20 mg/kg) on Days 1, 8, 15 and 22. In study 3, wounds were created on Day 12. On Days 4, 8, and 11 relative to wound creation, two randomized incisions per animal were evaluated with a Biomechanical Tissue Characterization System. Results: In Study 1, there was a statistically significant reduction in wound strength in the dexamethasone treated group on Day 11 as compared to saline negative control. There was a statistically significant reduction in wound strength in the anti-VEGF mAb treated animals on Day 8 as compared to saline in Study 2. Statistical evaluation of wound strength between saline treated animals and the anti-VEGF mAb treated animals showed a significant reduction in wound strength in the anti-VEGF mAb treatment group on Day 8 ( Fig. 3). In all studies there were open wound sites at the time of evaluation, which ranged from 6 to 50% on Day 4, 3 to 17% on Day 8, and 6% on Day 11. Discussion: These studies demonstrate a potential method for evaluating the strength of sterile incisional wounds in the cynomolgus monkey, which allows for multiple evaluations of wound strength within an animal over time in a non-terminal model. Dexamethasone and anti-VEGF mAb produced significant reductions in wound healing on Day 11 and 8, respectively. It was inconclusive whether the number of open incisional sites was related to the test article, incomplete closure at the time of surgery, or movement of the animals in the primate jacket. (C) 2007 Elsevier Inc. All rights reserved.