Dominique Pioletti

Biography

Dominique Pioletti received his Master in Physics from the Swiss Federal Institute of Technology Lausanne (EPFL) in 1992. He pursued his education in the same Institution and obtained his PhD in biomechanics in 1997. He developed original constitutive laws taking into account viscoelasticity in large deformations. Then he spent two years at UCSD as post-doc fellow acquiring know-how in cell and molecular biology. He was interested in particular to gene expression of bone cells in contact to orthopedic implant. In April 2006, Dominique Pioletti was appointed Assistant Professor tenure-track at the EPFL and is director of the Laboratory of Biomechanical Orthopedics. His research topics include biomechanics and tissue engineering of musculo-skeletal tissues; mechano-transduction in bone; development of orthopedic implant as drug delivery system. Since 2013, he has been promoted to the rank of Associate Professor.

Official source

https://people.epfl.ch/dominique.pioletti

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The drive to develop cartilage implants for the treatment of major defects in the musculoskeletal sys-tem has resulted in a major research thrust towards developing biomaterial devices for cartilage repair. Investigational devices for the restoration of articular cartilage are considered as significant risk mate-rials by regulatory bodies and therefore proof of efficacy and safety prior to clinical testing represents a critical phase of the multidisciplinary effort to bridge the gap between bench and bedside. To date, review articles have thoroughly covered different scientific facets of cartilage engineering paradigm, but surprisingly, little attention has been given to the preclinical considerations revolving around the valida-tion of a biomaterial implant. Considering hydrogel-based cartilage products as an example, the present review endeavors to provide a summary of the critical prerequisites that such devices should meet for cartilage repair, for successful implantation and subsequent preclinical validation prior to clinical trials. Considerations pertaining to the choice of appropriate animal model, characterization techniques for the quantitative and qualitative outcome measures, as well as concerns with respect to GLP practices are also extensively discussed. This article is not meant to provide a systematic review, but rather to intro-duce a device validation-based roadmap to the academic investigator, in anticipation of future healthcare commercialization.Statement of significance There are significant challenges around translation of in vitro cartilage repair strategies to approved ther-apies. New biomaterial-based devices must undergo exhaustive investigations to ensure their safety and efficacy prior to clinical trials. These considerations are required to be applied from early developmental stages. Although there are numerous research works on cartilage devices and their in vivo evaluations, little attention has been given into the preclinical pathway and the corresponding approval processes. With a focus on hydrogel devices to concretely illustrate the preclinical path, this review paper intends to highlight the various considerations regarding the preclinical validation of hydrogel devices for car-tilage repair, from regulatory considerations, to implantation strategies, device performance aspects and characterizations.(c) 2023 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

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Articular cartilage presents a mechanically sensitive tissue. Chondrocytes, the sole cell type residing in the tissue, perceive and react to physical cues as signals that significantly modulate their behavior. Hyaline cartilage is a connective tissue with high dissipative capabilities, able to increase its temperature during daily activities, thus providing a dynamic thermal milieu for the residing chondrocytes. This condition, self-heating, which is still chiefly ignored among the scientific community, adds a new thermal dimension in cartilage mechanobiology. Motivated by the lack of studies exploring this dynamic temperature increase as a potential stimulus in cartilage-engineered constructs, we aimed to elucidate whether loading-induced evolved temperature serves as an independent or complementary regulatory cue for chondrocyte function. In particular, we evaluated the chondrocytes' response to thermal and/or mechanical stimulation in two types of scaffolds exhibiting dissipation levels close to healthy and degenerated articular cartilage. It was found, in both scaffold groups, that the combination of dynamic thermal and mechanical stimuli induced superior effects in the expression of major chondrogenic genes, such as SOX9 and LOXL2, compared to either signal alone. Similar effects were also observed in proteoglycan accumulation over time, along with increased mRNA transcription and synthesis of TRPV4, and for the first time demonstrated in chondrocytes, TREK1 ion channels. Conversely, the chondrogenic response of cells to isolated thermal or mechanical cues was generally scaffold-type dependent. Nonetheless, the significance of thermal stimulus as a chondro-inductive signal was better supported in both studied groups. Our data indicates that the temperature evolution is necessary for chondrocytes to more effectively perceive and translate applied mechanical loading.

2023

Age- and sex-specific normative values of bone mineral density in the adult glenoid

Philippe Büchler, Alain Farron, Dominique Pioletti, Alexandre Terrier, Frédéric Vauclair

The objective of this study was to determine the normative bone mineral density (BMD) of cortical and trabecular bone regions in the adult glenoid and its dependence on the subject's age and sex. We analyzed computed tomography (CT) scans of 441 shoulders (310 males, 18-69 years) without any signs of glenohumeral joint pathology. Glenoid BMD was automatically quantified in six volumes of interest (VOIs): cortical bone (CO), subchondral cortical plate (SC), subchondral trabecular bone (ST), and three adjacent layers of trabecular bone (T1, T2, and T3). BMD was measured in Hounsfield unit (HU). We evaluated the association between glenoid BMD and sex and age with the Student's t test and Pearson's correlation coefficient (r), respectively. The lambda-mu-sigma method was used to determine age- and sex-specific normative values of glenoid BMD in cortical (CO and SC) and trabecular (ST, T1, T2, and T3) bone. Glenoid BMD was higher in males than females, in most age groups and most VOIs. Before 40 years old, the effect of age on BMD was very weak in both males and females. After 40 years old, BMD declined over time in all VOIs. This BMD decline with age was greater in females (cortical: r = -0.45, trabecular: r = -0.41) than in males (cortical: r = -0.30; trabecular: r = -0.32). These normative glenoid BMD values could prove clinically relevant in the diagnosis and management of patients with various shoulder disorders, in particular glenohumeral osteoarthritis and shoulder arthroplasty or shoulder instability, as well as in related research.

WILEY2022

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