Hyaluronic Acid-Based Hydrogel Coating Does Not Affect Bone Apposition at the Implant Surface in a Rabbit Model

Abstract

BackgroundUncemented orthopaedic implants rely on the bone-implant interface to provide stability, therefore it is essential that a coating does not interfere with the bone-forming processes occurring at the implant interface. In addition, local application of high concentrations of antibiotics for prophylaxis or treatment of infection may be toxic for osteoblasts and could impair bone growth.Questions/Purposes In this animal study, we investigated the effect of a commercially available hydrogel, either unloaded or loaded with 2% vancomycin. We asked, does unloaded hydrogel or hydrogel with vancomycin (1) interfere with bone apposition and timing of bone deposition near the implant surface; and (2) induce a local or systemic inflammatory reaction as determined by inflammation around the implant and hematologic parameters.MethodsIn 18 New Zealand White rabbits, an uncoated titanium rod (n = 6), a rod coated with unloaded hydrogel (n = 6), or a rod coated with 2% vancomycin-loaded hydrogel (n = 6) was implanted in the intramedullary canal of the left tibia. After 28 days, the bone volume fraction near the implant was measured with microCT analysis, inflammation was semiquantitatively scored on histologic sections, and timing of bone apposition was followed by semiquantitative scoring of fluorochrome incorporation on histologic sections. Two observers, blinded to the treatment, scored the sections and reconciled their scores if there was a disagreement. The hematologic inflammatory reaction was analyzed by measuring total and differential leukocyte counts and erythrocyte sedimentation rates in blood. With group sizes of six animals per group, we had 79% power to detect a difference of 25% in histologic scoring for infection and inflammation.ResultsNo differences were found in the amount of bone apposition near the implant in the No Gel group (48.65% ± 14.95%) compared with the Gel group (59.97% ± 5.02%; mean difference [MD], 11.32%; 95% CI, −3.89% to 26.53%; p = 0.16) or for the Van2 group (56.12% ± 10.06%; MD, 7.46; 95% CI, −7.75 to 22.67; p = 0.40), with the numbers available. In addition, the scores for timing of bone apposition did not differ between the No Gel group (0.50 ± 0.55) compared with the Gel group (0.33 ± 0.52; MD, −0.17; 95% CI, −0.86 to 0.53; p = 0.78) or the Van2 group (0.83 ± 0.41; MD, 0.33; 95% CI, −0.36 to 1.03; p = 0.42). Furthermore, we detected no differences in the histopathology scores for inflammation in the No Gel group (2.33 ± 1.67) compared with the Gel group (3.17 ± 1.59; MD, 0.83; 95% CI, −0.59 to 2.26; p = 0.31) or to the Van2 group (2.5 ± 1.24; MD, 0.17; 95% CI, −1.26 to 1.59; p = 0.95). Moreover, no differences in total leukocyte count, erythrocyte sedimentation rate, and neutrophil, monocyte, eosinophil, basophil, and lymphocyte counts were present between the No Gel or Van2 groups compared with the Gel control group, with the numbers available.ConclusionThe hydrogel coated on titanium implants, unloaded or loaded with 2% vancomycin, had no effect on the volume or timing of bone a...

Prophylaxis of implant-related infections by local release of vancomycin from a hydrogel in rabbits

“…Will the bioglass be in contact with the rabbit bone or will it be shielded? Authors: The empty hydrogel has proven to have no influence on bone apposition in a non-infected animal model with an implant (Boot et al, 2017). Although the bioglass is mixed with the hydrogel, it could be possible that the ions released from the bioglass are also released from the hydrogel; however, this was not tested.…”

“…Release studies showed that 2 % (w/v) vancomycin-loaded DAC ® releases over 80 % of the antibiotic within the first 24 h of in vitro incubation (Giavaresi et al, 2014), demonstrating that DAC ® can facilitate a fast delivery of the loaded agent. Furthermore, the hydrogel, when coated on titanium implants, has no effect on the volume or timing of bone growth near the implant and does not induce an inflammatory reaction in a rabbit implant-model (Boot et al, 2017). Also, the hydrogel loaded with antibiotics (e.g.…”

Hyaluronic-Based Antibacterial Hydrogel Coating for Implantable Biomaterials in Orthopedics and Trauma: From Basic Research to Clinical Applications

“…recent paper, focused on the impact on bone healing and implant osteointegration, reported no detrimental effects of vancomycin-loaded DAC ® or of DAC ® alone [57].…”

Biomaterial‐based possibilities for managing peri‐implantitis

“…This hydrogel engine was shown effective as a coating on titanium implants without inducing an inflammatory reaction. The idea was to develop an antibiotic‐loaded hydrogel loaded to offer a local protection for implants against bacteria without interfering with bone apposition or inducing a local or systemic inflammatory reaction . The versatility of hydrogels and the succeeded in vitro and in vivo outcomes makes it an interesting candidate to counteract implant‐related infections.…”