In vivo efficacy proof of concept of a large-size bioprinted dermo-epidermal substitute for permanent wound coverage.

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.

Immediate Proximal Row Carpectomy for Severe Perilunate Dislocation Injuries: A Minimum 5-Year Follow-Up.

Background: In patients with perilunate injuries (PLI) with multiple ligamentous and bony injuries involving the proximal carpal row, open reduction and internal fixation (ORIF) can be difficult and lead to poor functional outcomes. Proximal row carpectomy (PRC) is an alternative procedure that has been used for severely comminuted fractures. The aim of our study is to evaluate the long-term functional outcome (minimum 5 years) of patients that underwent an emergency PRC for PLI. Methods: We conducted a retrospective study of patients who underwent PRC at our centre between 2001 and 2016. Only patients with follow-up data of more than 5 years were included in the study. We evaluated range of motion, grip strength, Mayo Modified Wrist Score (MMWS) and Quick Disabilities of Arm, Shoulder and Hand (Quick-DASH). Radiographic analyses were performed to assess the presence of radiocarpal osteoarthritis and the space between the radius and capitate. Results: Thirteen patients were included, with an average follow-up of 78.07 months (6.5 years). The MMWS was 65 points (four excellent and good, four fair and five poor results) and the Quick-DASH score was 30 points. X-ray analysis reported only 15.3% of patients with radiocarpal arthrosis and an average radio-capitate joint space of 1.92 mm. Conclusions: The outcomes of PRC in the management of PLI are comparable to the results reported in literature for conventional ORIF. PRC is a simpler procedure that minimises the need for re-intervention. Level of Evidence: Level IV (Therapeutic).

Adipose Tissue and Adipose-Tissue-Derived Cell Therapies for the Treatment of the Face and Hands of Patients Suffering from Systemic Sclerosis.

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.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Anatomical study of the clitoris and its implications on female genital mutilation and surgical repair.

BACKGROUND: Worldwide, 200 million girls and women have been subjected to female genital mutilation. To restore the clitoral function and vulvar anatomy, clitoral repair has been performed since the 2000s. Nevertheless, there is a lack of precise and comprehensive data on the clitoral anatomy during surgical repair. This study aimed to precisely describe the terminal anatomies of the dorsal nerve and artery of the clitoris, and the clitoral neurovascular flap advancement for reconstruction in patients with female genital mutilation. METHODS: This study was performed on seven fresh female cadavers. The site of origin, diameter, length, and trajectory of each nerve and artery were recorded. The clitoral neurovascular flap advancement was measured after a midline transection of the suspensory ligament was performed and after extensive liberation of the dorsal bundles at their emergence from the pubic rami. RESULTS: At the distal point of the clitoral body, the width of the dorsal nerve and artery was 1.9 ± 0.3 mm and 0.9 ± 0.2 mm, respectively. The total length of the dorsal bundles was 6.6 cm (± 0.4). The midpart of the suspensory ligament was sectioned, which allowed a mean anteroposterior mobility of 2.7 cm (± 0.2). Extensive dissection of the neurovascular bundles up to their point of emergence from the suspensory ligament allowed a mean mobility of 3.4 ± 0.2 cm. CONCLUSION: We described the anatomical characteristics of the dorsal nerve and artery of the clitoris and the mobility of the clitoral neurovascular flap for reconstruction post clitoridectomy. This was done to restore the anatomic position of the glans clitoris while preserving and potentially restoring clitoral function in patients with female genital mutilation.

The Use of Higher Proportions of Platelet-Rich Plasma to Enrich Microfat Has Negative Effects: A Preclinical Study.

BACKGROUND: Platelet-rich plasma improves engraftment after fat transfer. However, the effects of platelet dose have never been investigated. The authors used magnetic resonance imaging to compare surviving graft volumes in mice after administration of four different formulations (microfat alone, and three platelet-rich plasma-enriched microfat mixes). METHODS: The authors used a random, double-blinded, fat transfer protocol using three different platelet levels: 1 million (low-dose), 500 million (medium-dose), and 1000 million (high-dose) platelets/ml, and fat alone (control). The authors grafted 0.4 ml of the 70/30 platelet-rich plasma-enriched microfat mixtures (0.4 million, 200 million, and 400 million platelets per 0.12 ml for the low-dose, medium-dose, and high-dose mixtures, respectively) or 0.4 ml of microfat alone into 22 nude mice and monitored surviving graft volumes every month for 3 months. Then, the authors histologically analyzed all grafts to assess neoangiogenesis status and fat integrity. RESULTS: Three-dimensional magnetic resonance imaging showed that the median surviving graft volumes at 3 months were 9.5 percent (interquartile range, 0 to 25 percent; p = 0.003) (high-dose), 4.1 percent (interquartile range, 0 to 18 percent; p = 0.001) (medium-dose), and 18 percent (interquartile range, 8 to 38 percent; p = 0.41) (low-dose) compared to 36 percent (interquartile range, 28 to 53 percent) for the control value. The histologic integrity of microfat-alone grafts was significantly better than those of the other grafts, although the high-dose and low-dose grafts exhibited higher levels of neoangiogenesis. CONCLUSION: Higher platelet levels in microfat grafts were associated with poor graft survival in nude mice; a clinical review would be appropriate.

Tissue expansion of the lower limb: Retrospective study of 141 procedures in burn sequelae.

INTRODUCTION: Skin expansion in the lower limb is a difficult procedure with a significant rate of complications. We propose, in this retrospective mono centric study, a systematic review of our skin expansion procedures on the lower limb in burn sequelae with a 30-years follow-up. The objective was to evaluate the overall result of our procedure and present its technical specificities. METHOD: We have included all of our skin expansion procedure in burn sequelae of the lower limb that had ended at least 6 months ago. The primary study endpoint was the occurrence of a complication during the procedure. The surgical approaches were juxta-lesional. A juxta-lesion or radial incisions were made for remote valves. When prosthesis were removed, we performed advancement flaps. RESULTS: From 1987 to 2017, we performed 141 lower limb expansions in 73 patients (62 women for 11 men). The average duration of the inflation procedure was 100.5 days. At least one complication occurred for 29.1% of procedures. We have identified 44 complications. Among the 41 complicated procedures, 26 procedures (63.4%) failed in the final achievement of an expanded skin flap and 15 procedures (36.6%) were rescued after complication, leading to perform flaps. We recorded 115 (81.6%) completed procedures. CONCLUSION: The success of our expansion procedures in burn sequelae of lower limb is due to technical key points such as the choice of the prosthesis size, the position of the remote internal valve, the position of the drain and a delayed inflation start. Level IV.