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Open AccessArticle

The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response

1
Department of Oral and Maxillofacial Surgery, Division for Regenerative Orofacial Medicine, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
2
Department for Cell and Tissue Engineering, Institute of Biology and Human Genetics, University of Niš, Faculty of Medicine, Niš 18106, Serbia
3
Clinic of Small Animals, c/o Institute of Veterinary Anatomy, Histology and Embryology, Justus Liebig University of Giessen, 35392 Giessen, Germany
4
Department of Oral Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
5
BerlinAnalytix GmbH, 12109 Berlin, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(8), 1969; https://doi.org/10.3390/ijms20081969
Received: 26 March 2019 / Revised: 20 April 2019 / Accepted: 21 April 2019 / Published: 22 April 2019
(This article belongs to the Special Issue Biomaterials for Soft and Hard Tissue Regeneration)
Biphasic bone substitutes (BBS) are currently well-established biomaterials. Through their constant development, even natural components like hyaluronic acid (HY) have been added to improve both their handling and also their regenerative properties. However, little knowledge exists regarding the consequences of the addition of HY to their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted, aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY), combined with a BBS, on in vitro biocompatibility and in vivo tissue reaction. Established in vitro procedures, using L929 cells, were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo part of the study, calvarial defects were created in 20 Wistar rats and subsequently filled with BBS, and BBS combined with two different HMWHY amounts, i.e., BBS + HY(L) and BBS + HY(H). As controls, empty defects were used. Established histological, immunohistochemical, and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damage to the L929 cells and can be considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of pro-inflammatory macrophages (* p < 0.05), comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to BBS, while improving the material handling properties. View Full-Text
Keywords: hyaluronic acid; biphasic bone substitute; biocompatibility; tissue reaction; inflammation; macrophage; M1; M2; multinucleated giant cells hyaluronic acid; biphasic bone substitute; biocompatibility; tissue reaction; inflammation; macrophage; M1; M2; multinucleated giant cells
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Sieger, D.; Korzinskas, T.; Jung, O.; Stojanovic, S.; Wenisch, S.; Smeets, R.; Gosau, M.; Schnettler, R.; Najman, S.; Barbeck, M. The Addition of High Doses of Hyaluronic Acid to a Biphasic Bone Substitute Decreases the Proinflammatory Tissue Response. Int. J. Mol. Sci. 2019, 20, 1969.

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