Integrative tissue, cellular and molecular responsiveness of an innovative ex vivo model of the Staphylococcus aureus-mediated bone infection.

Osteomyelitis is a pathological condition of the bone, frequently associated with the presence of infectious agents - namely Staphylococcus aureus - that induce inflammation and tissue destruction. Recent advances in the understanding of its pathophysiology and the identification of innovative therapeutic approaches were gathered from experimental in vitro and in vivo systems. However, cell culture models offer limited representativeness of the cellular functionality and the cell-cell and cell-matrix interactions, further failing to mimic the three-dimensional tissue organization; and animal models allow for limited mechanistic assessment given the complex nature of systemic and paracrine regulatory systems and are endorsed with ethical constraints. Accordingly, this study aims at the establishment and assessment of a new ex vivo bone infection model, upon the organotypic culture of embryonic chicken femurs colonized with S. aureus, highlighting the model responsiveness at the molecular, cellular, and tissue levels. Upon infection with distinct bacterial inoculums, data reported an initial exponential bacterial growth, followed by diminished metabolic activity. At the tissue level, evidence of S. aureus-mediated tissue destruction was attained and demonstrated through distinct methodologies, conjoined with decreased osteoblastic/osteogenic and increased osteoclastic/osteoclastogenic functionalities-representative of the osteomyelitis clinical course. Overall, the establishment and characterization of an innovative bone tissue infection model that is simple, reproducible, easily manipulated, cost-effective, and simulates many features of human osteomyelitis, further allowing the maintenance of the bone tissue's three-dimensional morphology and cellular arrangement, was achieved. Model responsiveness was further demonstrated, showcasing the capability to improve the research pipeline in bone tissue infection-related research.

Alendronate induces skeletal alterations in the chicken embryonic development model.

Alendronate, a nitrogen-containing bisphosphonate, has reported long-term clinical success in the management of distinct bone-related conditions, particularly in the modulation of post-menopausal osteoporosis. Nonetheless, whether the inhibitory activity over osteoclastic cells' functionality is widely acknowledged, contradictory evidence arises from the assessment of alendronate activity over osteoblastic populations. This may be of particular relevance in situations in which bone formation exceeds bone resorption, with further emphasis on embryonic development, since alendronate can cross the placental barrier and alendronate-based therapies are being extended into women of reproductive age. Accordingly, the present study aims to assess the effects of alendronate, at distinct concentrations (1.5E-10M to 1.5E-7M) on bone tissue development, within a translational animal model - the embryonic chicken development model. Embryos, at the beginning of osteogenesis (day 7) were exposed to different alendronate concentrations for 4 days. Embryos were following characterized for skeletal development by histomorphometric analysis upon histochemical staining, microtomographic analysis, and gene expression assessment of genes related to osteoclastogenic/osteoclastic and osteoblastogenic/osteogenic differentiation, as well as to the immuno-inflammatory activation. The findings revealed that exposure to alendronate had a dose-dependent impact on skeletal growth and mineralization. This effect was evidenced by diminished bone volume and reduced bone surface parameters, with the 1.5E-7M concentration leading to a remarkable reduction of over 50%. Additionally, a decreased osteoclastogenic/osteoclastic gene expression was verified, associated with a diminished osteoblastogenic/osteogenic program - within the 30-50% range for 1.5E-7 M, supporting the diminished bone formation process. An increased inflammatory activation may contribute, at least in part, to the attained outcomes. Overall present findings suggest a negative influence of alendronate on the embryonic bone development process in a dose-dependent manner, highlighting the potential risk of alendronate use during embryonic development.

Molecular and Cellular Aspects of Socket Healing in the Absence and Presence of Graft Materials and Autologous Platelet Concentrates: a Focused Review.

OBJECTIVES: The present manuscript aims to critically detail the physiologic process of socket healing, in the absence or presence of grafting materials or platelet concentrates, addressing the associated molecular and cellular events that culminate in the restoration of the lost tissue architecture and functionality. MATERIAL AND METHODS: An electronic search in the National Library of Medicine database MEDLINE through its online site PubMed and Web of Science from inception until May 2019 was conducted to identify articles concerning physiologic process of socket healing, in the absence or presence of grafting materials or platelet concentrates. The search was restricted to English language articles without time restriction. Additionally, a hand search was carried out in oral surgery, periodontology and dental implants related journals. RESULTS: In total, 122 literature sources were obtained and reviewed. The detailed biological events, at the molecular and cellular level, that occur in the alveolus after tooth extraction and socket healing process modulated by grafting materials or autologous platelet concentrates were presented as two entities. CONCLUSIONS: Tooth extraction initiates a convoluted set of orderly biological events in the alveolus, aiming wound closure and socket healing. The healing process comprises a wide range of events, regulated by the interplay of cytokines, chemokines and growth factors that determine cellular recruitment, proliferation and differentiation in the healing milieu, in a space- and time-dependent choreographic interplay. Additionally, the healing process may further be modulated by the implantation of grafting materials or autologous platelet concentrates within the tooth socket, aiming to enhance the regenerative outcome.

The 2nd Baltic Osseointegration Academy and Lithuanian University of Health Sciences Consensus Conference 2019. Summary and Consensus Statements: Group I - Biological Aspects of Tooth Extraction, Socket Healing and Indications for Socket Preservation.

INTRODUCTION: The task of Group I was to review and update the existing data concerning the physiologic process of socket healing, in the absence or presence of grafting materials or platelet concentrates, addressing the associated molecular and cellular events that culminate in the restoration of the lost tissue architecture and functionality. The second task was to review current literature concerning extraction socket classification immediately following tooth extraction and the rationales for socket preservation/augmentation procedures and with reference to it suggest novel clinical decision tree for extraction socket preservation/augmentation in aesthetic and non-aesthetic area. MATERIAL AND METHODS: The main areas indicated by this group were as follows: socket healing process, including haemostasis and coagulation, inflammatory phase, proliferative phase, bone tissue modelling and remodelling; socket healing with graft materials and autologous platelet concentrates; extraction socket classifications; indications and reasons for extraction socket preservation/augmentation. The systematic reviews and/or meta-analyses were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. The literature in the corresponding areas of interest was screened and reported following the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. Method of preparation of the systematic reviews, based on comprehensive search strategies, was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic reviews and/or meta-analyses is presented in Preface chapter. RESULTS: The results and conclusions of the review process are presented in the respective papers. One theoretical review-analysis and one systematic review were performed. The group's general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article.