In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid

TY - JOUR

T1 - In Vivo Analysis of the Biocompatibility and Bone Healing Capacity of a Novel Bone Grafting Material Combined with Hyaluronic Acid

AU - Pröhl, Annica

AU - Batinic, Milijana

AU - Alkildani, Said

AU - Hahn, Michael

AU - Radenkovic, Milena

AU - Najman, Stevo

AU - Jung, Ole

AU - Barbeck, Mike

PY - 2021/5/1

Y1 - 2021/5/1

N2 - 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.

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.

KW - Animals

KW - Bone Regeneration/drug effects

KW - Bone Substitutes/chemistry

KW - Bone Transplantation

KW - Bone-Implant Interface/growth & development

KW - Humans

KW - Hyaluronic Acid/pharmacology

KW - Hydroxyapatites/pharmacology

KW - Materials Testing

KW - Osteogenesis/drug effects

KW - Rats

KW - Rats, Wistar

KW - Skull/drug effects

KW - Water/chemistry

KW - Wound Healing/drug effects

U2 - 10.3390/ijms22094818

DO - 10.3390/ijms22094818

M3 - SCORING: Journal article

C2 - 34062885

VL - 22

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 9

M1 - 4818

ER -