Free Bioverit ^® II Implants Coated with a Nanoporous Silica Layer in a Mouse Ear Model — A Histological Study

Abstract

The objective of this study is to evaluate the suitability of a mouse middle ear model for testing ossicular replacement materials. Twenty-four BALB/c mice are implanted with the bioglass-ceramic Bioverit Õ II which is coated with a silica-nanostructure or with plain Bioverit Õ II as a control. After 2, 6, and 12 weeks, 4 mice per group are sacrificed and both complete petrous bones are analyzed histologically. All implants revealed in situ an incipient growth of thin connective tissue layers over the surface, followed by a *Author to whom correspondence should be addressed. E-mail: Brandes.gudrun@mh-hannover.de spreading of epithelial cells. The osseogenic response which is increasing with time is more intense in the coated Bioverit Õ II specimens. The absence of inflammatory cells suggests an excellent biocompatibility of the silica nano structure. As the results are comparable to a study with the same materials in rabbits, the mouse model described is highly suitable for evaluation of new ossicular replacement materials. Additionally, by gene expression analysis a more detailed insight into cellular interactions of the middle ear is offered.

Nanoporous silica coatings on implant surfaces: characterization, stability, biocompatibility and drug release properties

“…No significant increase in immune response or inflammatory gene expression could be detected in the presence of the implants, indicating that the nanoporous silica coating was highly biocompatible. These results are in accord with previous histological analyses of Bioverit ® II implants coated with a nanoporous silica layer which were conducted in both rabbit and murine animal models [33][34][35]. Since gene array analysis was able to detect an inflammatory response in the case of iron implants, the method per se is sufficiently sensitive in our hands [36].…”

“…In the middle ear cavity of mice, Bioverit ® II samples with a nanoporous coating did not provoke any significant inflammatory reaction as substantiated here by the modern method of whole genome expression profiling. These results, together with data from animal experiments using rabbits [subcutaneous and in the middle ear [33][34][35], show that the nanoporous silica coating is highly biocompatible. The internal space and the increased surface area have shown to be highly suitable for applications as a drug reservoir for the binding and presenting bioactive substances [19,27,28].…”

“…In particular, mice are an extremely well-characterized animal model, allowing both in-depth histological as well as detailed molecular genetics analyses. For molecular characterization of the implant-tissue interactions, a newly established murine middle ear model was adapted [33]. Cylindrical Bioverit ® II implants with length and diameter both of 1 mm were coated with nanoporous silica and were inserted into the middle ear cavity.…”

“…Surgery was done as described previously [33]. Briefly, the animals were anesthetized by intraperitoneal injection of 10 mg kg -1 xylazin (Rompun ® 2%, Bayer Vital GmbH, Leverkusen, Germany) and 100 mg kg -1 ketamin (Albrecht, Aulendorf, Germany) and 5 mg kg -1 of carprofen (Rimadyl, Pfizer Pharma GmbH, Karlsruhe, Germany).…”

Biocompatibility of silver containing silica films on Bioverit® II middle ear prostheses in rabbits

“…4 The suitability of Bioverit Õ II as a substrate for total ossicular chain reconstructive prosthesis (TORPs) has been proven in several experiments before. [5][6][7] Also, nanoporous silica coatings offer a high material stability and well supportive effects on biocompatibility mediated by a slightly decreased differentiation of osteoblasts and an increased mucosal layer. 6 Additionally, this coating is also practical for diverse modulations of the surface of middle ear implants.…”