Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cross-Linked Hyaluronic Acid Slows Down Collagen Membrane Resorption in Diabetic Rats through Reducing the Number of Macrophages

Meizi Eliezer
* ,
Anton Sculean
ORCID logo ,
Richard J. Miron
ORCID logo ,
Carlos Nemcovsky
ORCID logo ,
Dieter D. Bosshardt
,
Masako Fujioka-Kobayashi
,
Miron Weinreb
,
Moses Ofer
Version 1 : Received: 10 April 2021 / Approved: 12 April 2021 / Online: 12 April 2021 (14:26:18 CEST)

How to cite: Eliezer, M.; Sculean, A.; Miron, R.J.; Nemcovsky, C.; Bosshardt, D.D.; Fujioka-Kobayashi, M.; Weinreb, M.; Ofer, M. Cross-Linked Hyaluronic Acid Slows Down Collagen Membrane Resorption in Diabetic Rats through Reducing the Number of Macrophages. Preprints 2021, 2021040317. https://doi.org/10.20944/preprints202104.0317.v1 Eliezer, M.; Sculean, A.; Miron, R.J.; Nemcovsky, C.; Bosshardt, D.D.; Fujioka-Kobayashi, M.; Weinreb, M.; Ofer, M. Cross-Linked Hyaluronic Acid Slows Down Collagen Membrane Resorption in Diabetic Rats through Reducing the Number of Macrophages. Preprints 2021, 2021040317. https://doi.org/10.20944/preprints202104.0317.v1

Abstract

Accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated its effect on the number of macrophages and endothelial cells (ECs) within the CM. Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and Transglutaminase II, respectively. Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and 4-fold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p<0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals.

Keywords

Hyaluronic acid; Diabetes; Rats; Macrophages; Blood vessels; Collagen membranes

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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