Improving Cutaneous Scar Formation by Controlling the Mechanical Environment Large Animal and Phase I Studies
Improving Cutaneous Scar Formation by Controlling the Mechanical Environment Large Animal and Phase I Studies
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DOI：
10.1097/sla.0b013e318220b159
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发表时间：
2011-08-01
影响因子：
9
通讯作者：
Longaker, Michael T.
中科院分区：
文献类型：
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作者：
Gurtner, Geoffrey C.;Dauskardt, Reinhold H.;Longaker, Michael T.
目的：验证皮肤创面机械环境可以控制瘢痕形成的假说。背景：机械力可以调节多种生物过程，但物理力在瘢痕形成中的作用尚不清楚。此外，用装置卸载皮肤创面的治疗效果还没有得到严格的测试。方法：利用机械调节聚合物装置操纵红色杜洛克猪闭合性皮肤创面的力学环境。8周后，对不同机械应力状态的创面进行纤维标记物的免疫组织化学分析。在I期临床研究中，9名接受择期腹部手术的患者一侧接受应力屏蔽聚合物治疗，另一侧作为标准护理。在术后8至12个月期间拍摄专业照片，并由外行人和专业小组使用视觉模拟标尺进行评估。本研究注册于ClinicalTrials.gov，编号NCT00766727。结果：与对照组和高应力状态相比，应力屏蔽使组织学瘢痕面积分别减少了6倍和9倍(P<；0.01)，并显著减少了促纤维化标志物的组织学表达。高张力伤口的闭合诱导了红色杜洛克人类似人的疤痕的形成，这种表型通过伤口的应力屏蔽有效地缓解。在人体研究中，与患者内部对照相比，腹部切口处的应力屏蔽显著改善了瘢痕外观(P=0.004)。结论：使用动态应力屏蔽聚合物装置对伤口环境进行机械操作可以显著减少瘢痕的形成。
Objective: To test the hypothesis that the mechanical environment of cutaneous wounds can control scar formation.Background: Mechanical forces have been recognized to modulate myriad biologic processes, but the role of physical force in scar formation remains unclear. Furthermore, the therapeutic benefits of offloading cutaneous wounds with a device have not been rigorously tested.Methods: A mechanomodulating polymer device was utilized to manipulate the mechanical environment of closed cutaneous wounds in red Duroc swine. After 8 weeks, wounds subjected to different mechanical stress states underwent immunohistochemical analysis for fibrotic markers. In a phase I clinical study, 9 human patients undergoing elective abdominal surgery were treated postoperatively with a stress-shielding polymer on one side whereas the other side was treated as standard of care. Professional photographs were taken between 8 and 12 months postsurgery and evaluated using a visual analog scale by lay and professional panels. This study is registered with ClinicalTrials.gov, number NCT00766727.Results: Stress shielding of swine incisions reduced histologic scar area by 6- and 9-fold compared to control and elevated stress states, respectively (P < 0.01 for both) and dramatically decreased the histologic expression of profibrotic markers. Closure of high-tension wounds induced human-like scar formation in the red Duroc, a phenotype effectively mitigated with stress shielding of wounds. In the study on humans, stress shielding of abdominal incisions significantly improved scar appearance (P = 0.004) compared with within-patient controls.Conclusions: These results indicate that mechanical manipulation of the wound environment with a dynamic stress-shielding polymer device can significantly reduce scar formation.