Abstract:
Wound dehiscence, oftentimes a result of the poor tensile strength of early healing wounds, is a significant threat to the post-operative patient, potentially causing life-threatening complications. Vanadate, a protein tyrosine phosphatase inhibitor, has been shown to alter the organisation of deposited collagen in healing wounds and significantly improve the tensile strength of incisional wounds in rats. In this study, we sought to explore the effects of locally administered vanadate on tensile strength and collagen organisation in both the early and remodelling phases of excisional wound healing in a murine model. Wild-type mice underwent stented excisional wounding on their dorsal skin and were divided equally into three treatment conditions: vanadate injection, saline injection control and an untreated control. Tensile strength testing, in vivo suction Cutometer analysis, gross wound measurements and histologic analysis were performed during healing, immediately upon wound closure, and after 4 weeks of remodelling. We found that vanadate treatment significantly increased the tensile strength of wounds and their stiffness relative to control wounds, both immediately upon healing and into the remodelling phase. Histologic analysis revealed that these biomechanical changes were likely the result of increased collagen deposition and an altered collagen organisation composed of thicker and distinctly organised collagen bundles. Given the risk that dehiscence poses to all operative patients, vanadate presents an interesting therapeutic avenue to improve the strength of post-operative wounds and unstable chronic wounds to reduce the risk of dehiscence.
摘要:
伤口开裂,通常是由于早期愈合伤口的拉伸强度差,是对术后病人的重大威胁,可能导致危及生命的并发症。Vanadate,一种蛋白酪氨酸磷酸酶抑制剂,已被证明可以改变愈合伤口中沉积的胶原蛋白的组织,并显着提高大鼠切口伤口的拉伸强度。在这项研究中,我们试图在小鼠模型中探讨局部施用钒酸对切除伤口愈合的早期和重塑阶段的抗张强度和胶原组织的影响。野生型小鼠在其背部皮肤上进行了支架切除损伤,并平均分为三种治疗条件:钒酸盐注射,生理盐水注射控制,和未经处理的对照。拉伸强度试验,体内吸力计分析,总体伤口测量,在愈合过程中进行组织学分析,伤口闭合后立即,经过四周的改造。我们发现,相对于对照伤口,钒酸盐处理显着增加了伤口的拉伸强度及其刚度,愈合后立即进入重塑阶段。组织学分析显示,这些生物力学变化可能是胶原蛋白沉积增加和由较厚且组织明显的胶原蛋白束组成的胶原蛋白组织改变的结果。鉴于裂开对所有手术患者构成的风险,Vanadate提供了一种有趣的治疗途径,可以改善术后伤口和不稳定慢性伤口的强度,以降低开裂的风险。