Periodic Reporting for period 4 - BoneImplant (Monitoring bone healing around endosseous implants: from multiscale modeling to the patient’s bed) Periodo di rendicontazione: 2021-04-01 al 2022-06-30 Sintesi del contesto e degli obiettivi generali del progetto Population ageing explains the increasing interest in studying the osteoarticular system. Implanting biomaterials in bone to restore the organ functionality has allowed considerable progresses in orthopaedic and dental surgery. Despite a routine clinical use, implant failures, which may have dramatic consequences, still occur and are difficult to anticipate. Surgeons introduce biomaterials in a bone cavity formed by drilling, damaging bone tissue but also stimulating bone healing. To do so, non standardized empirical methods are often employed. During bone healing, ‘low level’ interfacial micromotions stimulate bone remodeling but fibrous tissue develops instead of bone in the case of ‘excessive’ relative micromotion between bone tissue and the implant surface. Failures are often due to degraded bone remodeling at the bone-implant interface, a multiscale phenomenon of an interdisciplinary nature which remains poorly understood. The aim of BoneImplant is to investigate the multi-time (from the microsecond up to the month) variations of the multiscale (from the nanometer to the organ scale) biomechanical properties of the bone-implant interface as a function of the implant environment, following an approach typical from engineering sciences. BoneImplant focuses on the description of the properties of bone tissue located around the implant during osseointegration. The originality of the approach lies in: i) multiphysical multimodality measurements, ii) the development of advanced multiscale bone model accounting for remodeling phenomena, isogeometric contact analysis and iii) the fundamental nature of this problem (understanding the time evolution of the properties of an interface) with important implications in terms of public health. Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti A methodology involving in vivo, in vitro and in silico approaches, which have been combined in an integrated manner, has been carried out and is described below. In vivo experiments were realized using titanium alloy (TiAl6V4) coin-shaped implants under different conditions. The advantage of this animal model is to consider a planar implant surface, which allows: i) standardized mechanical environmental conditions and ii) a proper initiation of crack path selection. Some implants were placed at around 200 µm from the leveled cortical bone surface, leading to an initially empty cavity (bone chamber), which allows to distinguish between mature and newly formed bone tissues. The effects of surface roughness, healing time and initial bone healing distance were investigated. A multimodality and multi-physical experimental approach has been carried out to assess the biomechanical properties of newly formed bone tissue as a function of the implant environment. Different techniques such as nanoindentation and micro Brillouin scattering were employed to assess the biomechanical properties of newly formed bone tissue around an implant. The experimental approach also allowed to estimate the effective adhesion energy and the potentiality of quantitative ultrasound imaging to assess different biomechanical properties of the interface.New modeling approaches have been developed in close synergy with the experiments. Isogeometric mortar formulation has allow to simulate the bone-implant interface in a stable and efficient manner. Moreover, finite element modeling has been carried out, allowing to understand the biomechanical determinant of primary and secondary stability. Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora) The integrative approach considered in BoneImplant allowed to pay a particular attention to characterizing the physical-biological microstructure (i.e. at relatively high resolution) at the implant interface in combination with the associated bone properties. Adapted analytical and numerical biomechanical modeling taking into account the coupling between the bi-phasic, multiscale and evolutive natures of bone tissue have been developed to optimize the conception of the experiments and to analyse the results. To do so, adhesive contact models coupled with homogenization approaches (mechanics and acoustics) have been considered. The scientific breakthrough consists in a better understanding of the biomechanical implant stability, which allows to derive: i) a better prediction of implant stability, ii) a better conception of the implants, iii) improved surgical strategies and iv) the development of an ultrasonic device to determine and predict implant stability. On the fundamental level, BoneImplant considers the development of advanced mechanical modeling. Considering the multiscale time evolution of the properties of an interface also has many implications in physics and engineering science (e.g. glassy materials, composite materials or nuclear industry).Results will be used to design effective loading clinical procedures of implants and to optimize implant conception, leading to the development of therapeutic and diagnostic techniques. The development of acoustic techniques to assess implant primary and secondary stability has led to the creation of the spin-off WaveImplant and to the project of another spin-off currently under creation. BoneImplant
