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Introduction: An autologous split-thickness skin graft (STSG) is a standard treatment for coverage of full-thickness skin defects. However, this technique has two major drawbacks: the use of general anesthesia for skin harvesting and scar sequelae on the donor site. In order to reduce morbidity associated with STSG harvesting, researchers have developed autologous dermo-epidermal substitutes (DESs) using cell culture, tissue engineering, and, more recently, bioprinting approaches. This study assessed the manufacturing reliability and in vivo efficacy of a large-size good manufacturing practice (GMP)-compatible bio-printed human DES, named Poieskin®, for acute wound healing treatment.Methods: Two batches (40 cm2 each) of Poieskin® were produced, and their reliability and homogeneity were assessed using histological scoring. Immunosuppressed mice received either samples of Poieskin® (n = 8) or human STSG (n = 8) immediately after longitudinal acute full-thickness excision of size 1 × 1.5 cm, applied on the skeletal muscle plane. The engraftment rate was assessed through standardized photographs on day 16 of the follow-up. Moreover, wound contraction, superficial vascularization, and local inflammation were evaluated via standardized photographs, laser Doppler imaging, and PET imaging, respectively. Histological analysis was finally performed after euthanasia.Results: Histological scoring reached 75% ± 8% and 73% ± 12%, respectively, displaying a robust and homogeneous construct. Engraftment was comparable for both groups: 91.8% (SD = 0.1152) for the Poieskin® group versus 100% (SD = 0) for the human STSG group. We did not record differences in either graft perfusion, PET imaging, or histological scoring on day 16.Conclusion: Poieskin® presents consistent bioengineering manufacturing characteristics to treat full-thickness cutaneous defects as an alternative to STSG in clinical applications. Manufacturing of Poieskin® is reliable and homogeneous, leading to a clinically satisfying rate of graft take compared to the reference human STSG in a mouse model. These results encourage the use of Poieskin® in phase I clinical trials as its manufacturing procedure is compatible with pharmaceutical guidelines.

Abstract Background Even though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria. Methods This retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality. Results Stromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% ± 4.30%) and recovery yield (2.54 × 105 ± 1.22 × 105 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 105 ± 1.11 × 105 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort). Conclusions Both centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 × 105 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed.

Adipose tissue is recognized as a valuable source of cells with angiogenic, immunomodulatory, reparative and antifibrotic properties and emerged as a therapeutic alternative for the regeneration and repair of damaged tissues. The use of adipose-tissue-based therapy is expanding in autoimmune diseases, particularly in Systemic Sclerosis (SSc), a disease in which hands and face are severely affected, leading to disability and a decrease in quality of life. Combining the advantage of an abundant supply of fat tissue and a high abundance of stem/stromal cells, fat grafting and adipose tissue-derived cell-based therapies are attractive therapeutic options in SSc. This review aims to synthesize the evidence to determine the effects of the use of these biological products for face and hands treatment in the context of SSc. This highlights several points: the need to use relevant effectiveness criteria taking into account the clinical heterogeneity of SSc in order to facilitate assessment and comparison of innovative therapies; second, it reveals some impacts of the disease on fat-grafting success; third, an important heterogeneity was noticed regarding the manufacturing of the adipose-derived products and lastly, it shows a lack of robust evidence from controlled trials comparing adipose-derived products with standard care.

No injection treatment has been proven to be effective in wrist osteoarthritis. When conservative measures fail, its management involves invasive surgery. Emergence of biotherapies based on adipose derived stem cells (ADSC) offers promising treatments for chondral degenerative diseases. Microfat (MF) and platelets-rich plasma (PRP) mixture, rich in growth factors and ADSC could be a minimally invasive injectable option in the treatment of wrist osteoarthritis. The aim of this uncontrolled prospective study was to evaluate the safety of a 4 mL autologous MF-PRP intra-articular injection, performed under local anesthesia. The secondary purpose was to describe the clinical and MRI results at 12 months of follow-up. Patients’ data collected were: occurrence of adverse effects, Visual analog scale (VAS), Disabilities of the Arm, Shoulder and Hand score (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores, wrist strength, wrist range of motion and 5-level satisfaction scale. No serious adverse event was recorded. A statistically significant decrease in pain, DASH, PRWE and force was observed at each follow-up. Our preliminary results suggest that intra-articular autologous MF and PRP injection may be a new therapeutic strategy for wrist osteoarthritis resistant to medical symptomatic treatment prior to surgical interventions.

Background: Breast implant infections are usually caused by Staphylococcus aureus and coagulase-negative staphylococci. Gram-negative bacilli are rarely reported to be involved in breast implant infections. Methods: Thirty-seven cases of microbiologically confirmed breast implant infection managed from January 2008 to June 2012 in the study centre were reviewed, including 10 cases from the study centre itself and 27 cases from private clinics in the region. Results: The prevalence of breast implant infection in the study centre was 0.74% of breast implantation, i.e., 3.23% in breast reconstruction for breast cancer and 0.27% in aesthetic breast augmentation (p = 0.0002). Of the 37 cases, 30% had undergone radiotherapy and 11% had undergone a lymph node dissection. S. aureus was identified in 18 cases, Gram-negative bacilli in 10 cases, coagulase-negative staphylococci in eight cases, anaerobic bacteria in eight cases, and streptococci in three cases. Pseudomonas aeruginosa was the second most commonly identified pathogen. Staphylococcus epidermidis was the most frequent coagulase-negative Staphylococcus species. In addition to Propionibacterium acnes and Actinomyces neuii, other facultative and strict anaerobic bacteria have not been reported before, e.g., Bacteroides thetaiotaomicron, Corynebacterium simulans, Dermabacter hominis, Finegoldia magna, and Peptoniphilus harei. Seventy-percent of cases were treated by immediate implant removal. All cases treated only with antibiotics were treated with surgery at the second visit. Conclusions: The microbiological epidemiology was noted by an increasing the proportion of Gram-negative bacteria and anaerobic bacteria detected with the advent of MALDI-TOF MS and molecular identification for diagnosis.

Wrist osteoarthritis (OA) is one of the most common conditions encountered by hand surgeons with limited efficacy of non-surgical treatments. The purpose of this study is to describe the Platelet-Rich Plasma (PRP) mixed-microfat biological characteristics of an experimental Advanced Therapy Medicinal Product (ATMP) needed for clinical trial authorization and describe the clinical results obtained from our first three patients 12 months after treatment (NCT03164122). Biological characterization of microfat, PRP and mixture were analysed in vitro according to validated methods. Patients with stage four OA according to the Kellgren Lawrence classification, with failure to conservative treatment and a persistent daily painful condition >40 mm according to the visual analog scale (VAS) were treated. Microfat-PRP ATMP is a product with high platelet purity, conserved viability of stromal vascular fraction cells, chondrogenic differentiation capacity in vitro and high secretion of IL-1Ra anti-inflammatory cytokine. For patients, the only side effect was pain at the adipose tissue harvesting sites. Potential efficacy was observed with a pain decrease of over 50% (per VAS score) and the achievement of minimal clinically important differences for DASH and PRWE functional scores at one year in all three patients. Microfat-PRP ATMP presented a good safety profile after an injection in wrist OA. Efficacy trials are necessary to assess whether this innovative strategy could delay the necessity to perform non-conservative surgery.

Sternum and rib osteomyelitis complicated from breast implant infection is rare. We report a case of early sternum and rib osteomyelitis occurred during breast implant infection managed in an inter-regional referral center for bone/joint infections in the south of France.

Les évaluateurs constituent un maillon essentiel des dispositifs d’évaluation des compétences langagières et doivent bénéficier d’un accompagnement continu pour maintenir la qualité des évaluations à un niveau satisfaisant. Cet article compare deux méthodes pour la détermination des profils de sévérité d’évaluateurs d’une épreuve d’expression écrite en français langue étrangère, à partir de leurs données de production. La première méthode s’inscrit dans le cadre de la théorie classique des tests et la seconde s’appuie sur la théorie de réponse aux items, par la mise en oeuvre d’un modèle multifacettes de Rasch. Les résultats concordants des deux méthodes montrent l’utilité de tenir compte de la sévérité des correcteurs aux différents points de césure pour améliorer la fidélité du test, même si cette dernière n’explique qu’une part limitée de la variance d’erreur. Ces informations permettent également de dresser des profils d’évaluation individuels des correcteurs, qui peuvent être exploités dans le cadre de leur suivi pour la mise en oeuvre d’actions de remédiation ciblées.

Le contrôle de la qualité des évaluations des productions écrites en français langue étrangère pose de nombreuses questions, encore amplifiées lorsqu’il s’agit de tests à forts enjeux pour les candidats. Cet article illustre comment ce contrôle peut s’appuyer à la fois sur la théorie de la généralisabilité et sur le modèle multifacettes de Rasch pour relever les sources d’erreur (stabilité inter- et intracorrecteurs, variation des stimuli fournis aux candidats pour produire leurs textes…) et en estimer l’importance respective dans le cadre d’un monitorage de la qualité d’une épreuve de français langue étrangère.