Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver - Anschutz Medical Campus and Colorado Children's Hospital, Aurora, CO.
Department of Surgery, Comprehensive Wound Center, Ohio State University Medical Center, Columbus, OH.
J Am Coll Surg. 2019 Jan;228(1):107-115. doi: 10.1016/j.jamcollsurg.2018.09.017. Epub 2018 Oct 22.
Diabetic wounds have become one of the most challenging public health issues of the 21st century, yet there is no effective treatment available. We have previously shown that the diabetic wound healing impairment is associated with increased inflammation and decreased expression of the regulatory microRNA miR-146a. We have conjugated miR-146a to cerium oxide nanoparticles (CNP-miR146a) to target reactive oxygen species (ROS) and inflammation. This study aimed to evaluate the consequences of CNP-miR146a treatment of diabetic wounds.
Eight-millimeter wounds were created on the dorsal skin of Db/Db mice and treated with PBS or differing concentrations of CNP-mir146a (1; 10; 100; or 1,000 ng) at the time of wounding. Rate of wound closure was measured until the wounds were fully healed. At 4 weeks post-healing, a dumbbell-shaped skin sample was collected, with the healed wound in the center, and an Instron 5942 testing unit was used to measure the maximum load and modulus.
Our data showed that diabetic wounds treated with PBS or 1 ng CNP-miR146a took 18 days to heal. Treatment with 10, 100, or 1,000 ng of CNP+miR-146a effectively enhanced healing, and wounds were fully closed at day 14 post-wounding. The healed skin from the CNP-miR146a-treated group showed a trend of improved biomechanical properties (increased maximum load and modulus), however it did not reach significance.
We found that a 100-ng dose of CNP-miR146a improved diabetic wound healing and did not impair the biomechanical properties of the skin post-healing. This nanotechnology-based therapy is promising, and future studies are warranted to transfer this therapy to clinical application.
糖尿病伤口已成为 21 世纪最具挑战性的公共卫生问题之一，但目前尚无有效的治疗方法。我们之前的研究表明，糖尿病伤口愈合受损与炎症增加和调节 microRNA miR-146a 的表达减少有关。我们已经将 miR-146a 与氧化铈纳米粒子（CNP-miR146a）缀合，以靶向活性氧（ROS）和炎症。本研究旨在评估 CNP-miR146a 治疗糖尿病伤口的后果。
在 Db/Db 小鼠的背部皮肤创建 8 毫米的伤口，并在受伤时用 PBS 或不同浓度的 CNP-mir146a（1；10；100；或 1,000 ng）处理。测量伤口闭合率，直到伤口完全愈合。在愈合后 4 周，收集哑铃形皮肤样本，愈合伤口位于中心，使用 Instron 5942 测试单元测量最大负载和模量。
我们的数据表明，用 PBS 或 1 ng CNP-miR146a 治疗的糖尿病伤口需要 18 天才能愈合。用 10、100 或 1,000 ng 的 CNP+miR-146a 治疗可有效促进愈合，伤口在受伤后 14 天完全闭合。从 CNP-miR146a 处理组的愈合皮肤中观察到生物力学性能（最大负载和模量增加）改善的趋势，但未达到显著水平。
我们发现 100 ng 剂量的 CNP-miR146a 可改善糖尿病伤口愈合，且不会损害愈合后皮肤的生物力学性能。这种基于纳米技术的治疗方法很有前途，需要进一步的研究将该疗法转化为临床应用。
