title: A Bone-Implant Interaction Mouse Model for Evaluating Molecular Mechanism of Biomaterials/Bone Interaction.
abstract: The development of an optimal animal model that could provide fast assessments of the interaction between bone and orthopedic implants is essential for both preclinical and theoretical researches in the design of novel biomaterials. Compared with other animal models, mice have superiority in accessing the well-developed transgenic modification techniques (e.g., cell tracing, knockoff, knockin, and so on), which serve as powerful tools in studying molecular mechanisms. In this study, we introduced the establishment of a mouse model, which was specifically tailored for the assessment of bone-implant interaction in a load-bearing bone marrow microenvironment and could potentially allow the molecular mechanism study of biomaterials by using transgenic technologies. The detailed microsurgery procedures for developing a bone defect (Φ = 0.8 mm) at the metaphysis region of the mouse femur were recorded. According to our results, the osteoconductive and osseointegrative properties of a well-studied 45S5 bioactive glass were confirmed by utilizing our mouse model, verifying the reliability of this model. The feasibility and reliability of the present model were further checked by using other materials as objects of study. Furthermore, our results indicated that this animal model provided a more homogeneous tissue-implant interacting surface than the rat at the early stage of implantation and this is quite meaningful for conducting quantitative analysis. The availability of transgenic techniques to mechanism study of biomaterials was further testified by establishing our model on Nestin-GFP transgenic mice. Intriguingly, the distribution of Nestin+cells was demonstrated to be recruited to the surface of 45S5 glass as early as 3 days postsurgery, indicating that Nestin+lineage stem cells may participate in the subsequent regeneration process. In summary, the bone-implant interaction mouse model could serve as a potential candidate to evaluate the early stage tissue response near the implant surface in a bone marrow microenvironment, and it also shows great potential in making transgenic animal resource applicable to biomaterial studies, so that the design of novel biomaterials could be better guided.
authors.affiliation: 1 Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences, Shenzhen, China .|2 Department of Orthopedics and Traumatology, Faculty of Medicine, The University of Hong Kong , Hong Kong .
authors.forename: Wenlong
authors.initials: W
authors.lastname: Liu
authors.affiliation: 3 School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong , Hong Kong .
authors.forename: Xiuli
authors.initials: X
authors.lastname: Dan
authors.affiliation: 1 Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences, Shenzhen, China .|4 Shenzhen Key Laboratory for Innovative Technology in Orthopedic Trauma, Department of Orthopedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, University of Hong Kong , Shenzhen, China .
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: 2 Department of Orthopedics and Traumatology, Faculty of Medicine, The University of Hong Kong , Hong Kong .
authors.forename: William W
authors.initials: WW
authors.lastname: Lu
authors.affiliation: 1 Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences, Shenzhen, China .
authors.forename: Haobo
authors.initials: H
authors.lastname: Pan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016348:Osseointegration / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001672:Biocompatible Materials
keywords: animal model; bone–implant interaction; molecular mechanism; transgenic