Dunn Louise, Prosser Hamish C G, Tan Joanne T M, Vanags Laura Z, Ng Martin K C, Bursill Christina A
The Heart Research Institute.
J Vis Exp. 2013 May 28(75):e50265. doi: 10.3791/50265.
Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.
伤口愈合与修复是人类生命中最复杂的生物过程。受伤后，多种生物途径会被激活。例如，糖尿病患者出现的伤口愈合受损可能会导致截肢等严重不良后果。因此，开发促进伤口修复的新型药物的需求日益迫切。对这些药物的测试一直局限于猪等大型动物模型，而这些模型往往不切实际。小鼠是理想的临床前模型，因为它们经济实惠且易于进行基因操作，便于进行机制研究。然而，小鼠的伤口愈合与人类有根本不同，因为它主要通过收缩来实现。我们的小鼠模型通过在伤口周围使用夹板克服了这一问题。通过固定伤口，修复过程就依赖于上皮形成、细胞增殖和血管生成，这与人类伤口愈合的生物过程极为相似。虽然需要保持一致性和小心操作，但这个小鼠模型并不涉及复杂的手术技术，并且能够对例如促进血管生成或抑制炎症的有前景的药物进行有力测试。此外，由于制备了两个伤口，每只小鼠自身就作为对照，使得可以在同一只动物上同时应用测试化合物和赋形剂对照。总之，我们展示了一个实用、易于操作且可靠的伤口愈合模型，它与人类的伤口愈合模型相当。
