The Effect Of Cross-linked Hyaluronic Acid For Reducing Adhesion As A Middle Ear Packing Agent:an Experimental Study

Background and objectiveEven now we are trying to develop an ideal middle ear(ME) packing material for ossiculoplasty, tympanoplasty, or other otologic procedures.Cross-linked hyaluronic acid has been used to prevent postoperative adhesion in department of General Surgery, Gynecology and Orthopedics. However, the safety and efficacy of using cross-linked hyaluronic acid in middle ear surgery have not been thoroughly studied.Materials and methodsSeveral materials are prepared, namely, Gelfoam (absorbable gelatin sponge), MeroGel(esterified hyaluronic acid), PureRegen Gel Oto I (cross-linked hyaluronic acid), PureRegen Gel Oto II(cross-linked hyaluronic acid) are prepared.The animals were divided into six groups:group1, going through myringotomy, PureRegen Gel Oto I-treated; group2, going through myringotomy, with no packing material; group3-6, the middle ear mucosa is abraded using a pick through a myringotomy incision and then group3, PureRegen Gel Oto I-treated, group4, Gelfoam-treated; group5, Merogel-treated; group6, PureRegen Gel Oto II-treated. In every group, the study is performed on24guinea pigs.1week,2weeks,4weeks and6weeks after operation,4guinea pigs of each group are examed for results. Preoperative and posteroperative auditory brainstem response studies are performed by commercial electrophysiology equipment, then the animals are killed and the temporal bones are harvested. Whole temporal bone sectioning is performed to analyze the presence of implant, surrounding inflammation, presence of osteoneogenesis and fibrosis, or adhesions.Results The ABR results at the end of postoperative week1show there is statistically significant difference for myringotomy and postpacking between group2,4and group1,3,5,6. Group4is even worse than group2. At the end of postoperative week2, there is statistically significant difference between group2and the others, the former is worse. At the end of postoperative week4, group2and4are statistically significantly different from the others, however, group2is worse than group4. At the end of postoperative week6, group2and4are better than week4, but still statistically significantly different from the others.The Gelfoam group still has implant present at the end of postoperative week6, while the other groups has little left at the end of postoperative week2.The tympanic membrane(TM) incision closes up generally at the end of postoperative week1in group1,3,5,6without scar or adhesion formation. TM incision closes up at the same time, but25%heels with scar, and has the complication of ME mucosa adhesion later.There is no ME mucosa fibrosis, thickening or adhesion formation in group1at any time point.By electronic otoscope, there has been inflammation reaction surround the abraded ME mucosa in group2,3,4,5,6since, including ME mucosa edema and effusion. Group2and4shows more severe, with ME mucosa adhesion later than week4.There is no postoperative infection in group1,3,4,5,6. one of group2shows purulent secretion.By histopathology, there has been inflammation reaction surround the abraded ME mucosa in group2,3,4,5,6since postoperative week1, including mucosa thickness, blood vessel expanded. At the end of week2, Group2shows more severe inflammation reaction, having showed ME mucosa adhesion and fibrosis. And there is statistically significant difference between group2and4. At the end of week1and week6, Group4shows more severe inflammation reaction, having showed ME mucosa adhesion and fibrosis.There is no statistically significant difference between group3,5,6. No osteoneogenesis is observed.ConclusionOur results show that PureRegen Gel Oto I and II are non-ototoxic and biocorapatible within the guinea pig’s ME cavity. They don’t trigger inflammation reaction in integral ME mucosa. They lighten inflammation reaction in tissue surround abraded ME mucosa, effectively prevent adhesion formation. It can be syringed into ME cavity, then less risky for postoperative infection. The implant can last for about2weeks, neither too short for supporting surrounding ME structure, nor too long to trigger foreign body reaction.Therefore, these results suggest that PureRegen Gel Oto I and II could be used safely and effectively as a ME packing agent during otologic procedures.