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The Role of Hyaluronidase for the Skin Necrosis Caused by Hyaluronic Acid Injection-Induced Embolism: A Rabbit Auricular Model Study

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Skin necrosis is considered the most serious complication of hyaluronic acid dermal filler injection procedures. To effectively treat skin necrosis, hyaluronidase injection is one of the essential preventative treatments, and yet optimal complication management remains an unmet need. Therefore, this paper investigates the effects of hyaluronidase injection timing on the treatment of skin necrosis.


In an in vitro experiment, the carbazole method was used to determine the degradation time of hyaluronic acid gels in a large volume of hyaluronidase. In vivo experimental rabbit ear models were developed to simulate the skin necrosis caused by hyaluronic acid and the test animals distributed into five groups. Except one control group, the other four groups were injected with a large volume of hyaluronidase as treatment at 2 h, 4 h, 8 h and 16 h, respectively, after models were built. The necrosis degree of models was analyzed with necrotic area and histologic examination on the postoperative 7th day. Besides, temperatures of rabbit ears were observed to demonstrate the healing process of flap models.


The average necrotic area of flaps in the 2-h and 4-h injection groups showed a significant difference compared with that of the control group (p < 0.05; p < 0.05). The histologic examination showed that there were HA embolisms, vascular thrombolytic recanalization and arteriovenous thromboses in the survival area. In addition, the mean temperatures of the rabbit ear flaps fluctuated over time and showed clear differences between distal and proximal parts.


The area of flap necrosis positively correlates with injection timing of the large volume of hyaluronidase. More importantly, when injection timing is within 4 h, treatment effectiveness will be significantly improved.

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This study was supported by National Natural Science Foundation of China (81470720, 31271032).

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Correspondence to Jihua Li.

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Li, J., Xu, Y., Wang, Y. et al. The Role of Hyaluronidase for the Skin Necrosis Caused by Hyaluronic Acid Injection-Induced Embolism: A Rabbit Auricular Model Study. Aesth Plast Surg 43, 1362–1370 (2019).

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