Hyaluronic acid slows down collagen membrane degradation in uncontrolled diabetic rats

Meizi Eliezer*, Anton Sculean, Richard J. Miron, Carlos Nemcovsky, Evegeny Weinberg, Miron Weinreb, Hasan Zoabi, Dieter D. Bosshardt, Masako Fujioka-Kobayashi, Ofer Moses

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Aim: To examine the in vitro biokinetics of hyaluronic acid (HA) from a collagen membrane (CM) and to evaluate the in vivo effect of immersion of the CM in HA solution on its degradation in streptozotocin (STZ)-induced diabetes conditions in a rat calvaria subcutaneous model. Background: CM degradation is accelerated in uncontrolled diabetic rats. Immersion of CM in HA has been suggested to decrease their resorption rate without interfering with their tissue integration and structural degradation. However, it is unknown to what extent CM degradation may be influenced by its immersion in HA solution under a condition mimicking a medically compromised situation with an increased inflammatory level such as diabetes. Materials and Methods: CMs were soaked in cross-linked HA. Protein adsorption and the HA release were quantified by ELISA. Diabetes was induced in sixteen rats, while 16 healthy rats served as control. CM was prepared and labeled prior to implantation with Biotin. Seventeen CM were immersed in HA and 17 CM in PBS. In each animal, one test or one control disk was implanted. In order to compare the collagen content, two similar non-implanted CM were used as baseline. Fourteen days after surgery, thirty-two animals were sacrificed. The entire calvaria including the skin above, was chemically fixed, decalcified, and embedded in paraffin. Five-μm-thick sections were analyzed histologically and histomorphometrically using H&E and avidin-peroxidase staining. Results: The in vitro results demonstrated that the CM adsorbed roughly 80% of the total HA content. After 10 days, 36.3% of the initial HA remained on the CM. The in vivo results demonstrated that diabetes significantly reduced the thickness of the CM, while HA had a significant effect on keeping the membrane thickness. HA increased the residual collagen content in the diabetic group (P < 0.0001) but no such effect was observed in the healthy group. Conclusion: Immersion of CM in HA prior to the implantation delays membrane degradation in uncontrolled diabetic compared with normoglycemic rats.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalJournal of Periodontal Research
Issue number6
StatePublished - 1 Dec 2019


  • collagen membrane
  • diabetes mellitus
  • guided bone regeneration
  • hyaluronic acid


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