Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 26 March 2019 / Approved: 28 March 2019 / Online: 28 March 2019 (06:54:57 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Int. J. Mol. Sci. 2019, 20, 1969
DOI: 10.3390/ijms20081969

Abstract

Biphasic bone substitutes (BBS) are nowadays established biomaterials. Through their constant development even natural components like hyaluronic acid (HY) are added to improve both their handling and also their regenerative properties. However, low knowledge exists regarding the consequences of the HY addition for 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 the in vitro biocompatibility and the 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 study part, calvarial defects were created in 20 Wistar rats and subsequently filled with the BBS and the 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 damages to the L929 cells and can 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 proinflammatory 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 the BBS while improving the material handling properties.

Subject Areas

hyaluronic acid; biphasic bone substitute; biocompatibility; tissue reaction; inflammation; macrophage; M1; M2; multinucleated giant cells

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