Statistical optimization of hyaluronidase production by Ochrobactrum intermedium MEFS strain along with in vivo application in the treatment of aesthetic filler complications

Abstract

This study aims to optimize the production of microbial hyaluronidase (hyase) from Ochrobactrum intermedium MEFS strain using a statistical model and assess its effectiveness in degrading dermal filler in hairless mice. Plackett-Burman design identified nicotinic acid and CaBr as the main factors affecting hyase activity, with optimal concentrations of 5.51 μg/mL for nicotinic acid and 99.76 mM for CaBr, resulting in hyase activity of 320 U/mL, as determined by a central compound design. The purified hyase was applied to hairless mice to reverse dermal filler complications. Complete degradation occurred after 48 h with 60 U/mL and 72 h with 30 U/mL treatments. Histological analysis showed a strong inflammatory response (neutrophiles accumulation) 24 h post-injection, which shifted to moderate inflammation (mononuclear cells) after 14 days. Hyase treatment reduced inflammation in a dose-dependent manner, with 30 U/mL resulting in mild inflammation and 60 U/mL promoting tissue repair. Histological analysis also revealed that the HA filler was completely eliminated when hyase was used at a dosage of 60 U/mL. This approach has proven more effective in completely eliminating the filler and supporting tissue regeneration. This is the first report of using microbial hyase in filler injections, offering potential for treating aesthetic filler complications.