Department of Cell Biology and Physiology, University of New Mexico HSC, Albuquerque, New Mexico 87131, USA.
J Surg Res. 2010 Nov;164(1):e201-12. doi: 10.1016/j.jss.2010.07.059. Epub 2010 Sep 17.
The delivery of proangiogenic agents in clinical trials of wound healing has produced equivocal results, the lack of real-time assessment of vascular growth is a major weakness in monitoring the efficacy of therapeutic angiogenesis, and surgical solutions fall short in addressing the deficiency in microvascular blood supply to ischemic wounds. Therefore, elucidation of the mechanisms involved in ischemia-induced blood vessel growth has potential diagnostic and therapeutic implications in wound healing.
Three surgical models of wound ischemia, a cranial-based myocutaneous flap, an identical flap with underlying silicone sheeting to prevent engraftment, and a complete incisional flap without circulation were created on C57BL6 transgenic mice. Laser speckle contrast imaging was utilized to study the pattern of ischemia and return of revascularization. Simultaneous analysis of wound histology and microvascular density provided correlation of wound perfusion and morphology.
Creation of the peninsular-shaped flap produced a gradient of ischemia. Laser speckle contrast imaging accurately predicted the spatial and temporal pattern of ischemia, the return of functional revascularization, and the importance of engraftment in distal flap perfusion and survival. Histologic analysis demonstrated engraftment resulted in flap revascularization by new blood vessel growth from the recipient bed and dilatation of pre-existing flap vasculature.
Further research utilizing this model of graded wound ischemia and the technology of laser speckle perfusion imaging will allow monitoring of the real-time restitution of blood flow for correlation with molecular biomarkers of revascularization in an attempt to gain further understanding of wound microvascular biology.
在创伤愈合的临床研究中,促血管生成剂的应用效果并不明确,缺乏对血管生长的实时评估是监测治疗性血管生成疗效的主要缺陷,而手术方法无法解决缺血创面微血管血供不足的问题。因此,阐明缺血诱导血管生长的机制在创伤愈合的诊断和治疗方面具有潜在意义。
在 C57BL6 转基因小鼠上建立了三种创伤缺血的手术模型,包括颅基肌皮瓣、具有防止植入的底层硅酮片的相同皮瓣,以及无循环的完全切开皮瓣。利用激光散斑对比成像技术研究缺血和再血管化的模式。同时分析创面组织学和微血管密度,提供创面灌注和形态的相关性。
创建半岛形皮瓣会导致缺血程度的梯度变化。激光散斑对比成像能够准确预测缺血的时空模式、功能性再血管化的恢复以及植入物对皮瓣远端灌注和存活的重要性。组织学分析表明,植入物通过从受体床长出新的血管和扩张皮瓣血管来促进皮瓣再血管化。
进一步利用这种分级创伤缺血模型和激光散斑灌注成像技术,将能够监测血流的实时恢复,并与血管生成的分子生物标志物相关联,以进一步了解创面微血管生物学。