PMID- 34062885 OWN - NLM STAT- MEDLINE DCOM- 20210628 LR - 20210628 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 9 DP - 2021 May 1 TI - In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid. LID - 10.3390/ijms22094818 [doi] LID - 4818 AB - The present in vivo study analyses both the inflammatory tissue reactions and the bone healing capacity of a newly developed bone substitute material (BSM) based on xenogeneic bone substitute granules combined with hyaluronate (HY) as a water-binding molecule. The results of the hyaluronate containing bone substitute material (BSM) were compared to a control xenogeneic BSM of the same chemical composition and a sham operation group up to 16 weeks post implantationem. A major focus of the study was to analyze the residual hyaluronate and its effects on the material-dependent healing behavior and the inflammatory tissue responses. The study included 63 male Wistar rats using the calvaria implantation model for 2, 8, and 16 weeks post implantationem. Established and Good Laboratory Practice (GLP)-conforming histological, histopathological, and histomorphometrical analysis methods were conducted. The results showed that the new hyaluronate containing BSM was gradually integrated within newly formed bone up to the end of the study that ended in a condition of complete bone defect healing. Thereby, no differences to the healing capacity of the control BSM were found. However, the bone formation in both groups was continuously significantly higher compared to the sham operation group. Additionally, no differences in the (inflammatory) tissue response that was analyzed via qualitative and (semi-) quantitative methods were found. Interestingly, no differences were found between the numbers of pro- and anti-inflammatory macrophages between the three study groups over the entire course of the study. No signs of the HY as a water-binding part of the BSM were histologically detectable at any of the study time points, altogether the results of the present study show that HY allows for an optimal material-associated bone tissue healing comparable to the control xenogeneic BSM. The added HY seems to be degraded within a very short time period of less than 2 weeks so that the remaining BSM granules allow for a gradual osteoconductive bone regeneration. Additionally, no differences between the inflammatory tissue reactions in both material groups and the sham operation group were found. Thus, the new hyaluronate containing xenogeneic BSM and also the control BSM have been shown to be fully biocompatible without any differences regarding bone regeneration. FAU - Prohl, Annica AU - Prohl A AUID- ORCID: 0000-0001-7251-7621 AD - BerlinAnalytix GmbH, 12109 Berlin, Germany. FAU - Batinic, Milijana AU - Batinic M AD - BerlinAnalytix GmbH, 12109 Berlin, Germany. FAU - Alkildani, Said AU - Alkildani S AUID- ORCID: 0000-0002-2629-4102 AD - BerlinAnalytix GmbH, 12109 Berlin, Germany. FAU - Hahn, Michael AU - Hahn M AD - Institute of Osteology and Biomechanics, Eppendorf University Hospital, University of Hamburg, 20246 Hamburg, Germany. FAU - Radenkovic, Milena AU - Radenkovic M AUID- ORCID: 0000-0003-0603-0684 AD - Department for Cell and Tissue Engineering, Faculty of Medicine, University of Nis, 18108 Nis, Serbia. FAU - Najman, Stevo AU - Najman S AUID- ORCID: 0000-0002-2411-9802 AD - Department for Cell and Tissue Engineering, Faculty of Medicine, University of Nis, 18108 Nis, Serbia. AD - Department of Biology and Human Genetics, Faculty of Medicine, University of Nis, 18108 Nis, Serbia. FAU - Jung, Ole AU - Jung O AUID- ORCID: 0000-0001-8005-2916 AD - Clinic and Policlinic for Dermatology and Venereology, University Medical Center Rostock, 18057 Rostock, Germany. FAU - Barbeck, Mike AU - Barbeck M AUID- ORCID: 0000-0002-3001-1347 AD - Department of Ceramic Materials, Chair of Advanced Ceramic Materials, Institute for Materials Science and Technologies, Technical University Berlin, 10623 Berlin, Germany. LA - eng PT - Journal Article DEP - 20210501 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Bone Substitutes) RN - 0 (Hydroxyapatites) RN - 059QF0KO0R (Water) RN - 9004-61-9 (Hyaluronic Acid) SB - IM MH - Animals MH - Bone Regeneration/drug effects MH - Bone Substitutes/chemistry/*pharmacology MH - *Bone Transplantation MH - Bone-Implant Interface/growth & development/pathology MH - Humans MH - Hyaluronic Acid/pharmacology MH - Hydroxyapatites/pharmacology MH - Materials Testing MH - Osteogenesis/*drug effects MH - Rats MH - Rats, Wistar MH - Skull/drug effects/*growth & development MH - Water/chemistry MH - Wound Healing/drug effects PMC - PMC8124336 OTO - NOTNLM OT - bone regeneration OT - hyaluronic acid OT - inflammation OT - macrophages OT - xenogeneic bone graft, immune response COIS- The authors declare no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/06/29 06:00 PMCR- 2021/05/01 CRDT- 2021/06/02 01:05 PHST- 2021/03/27 00:00 [received] PHST- 2021/04/26 00:00 [revised] PHST- 2021/04/28 00:00 [accepted] PHST- 2021/06/02 01:05 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/06/29 06:00 [medline] PHST- 2021/05/01 00:00 [pmc-release] AID - ijms22094818 [pii] AID - ijms-22-04818 [pii] AID - 10.3390/ijms22094818 [doi] PST - epublish SO - Int J Mol Sci. 2021 May 1;22(9):4818. doi: 10.3390/ijms22094818.