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    Effetti biologici delle forze meccaniche esterne sui tessuti molli: ottimizzazione preclinica per l'applicazione translazionale in chirurgia rigenerativa. Biological effects of external mechanical forces on soft tissues: preclinical optimization for translational application in regenerative surgery

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    In reconstructive surgery, tissues are routinely transferred to repair a defect caused by trauma, cancer, chronic diseases, or congenital malformations. Surgical transfer intrinsically impairs metabolic supply to tissues placing a risk for ischemic complications such as necrosis, impaired healing, or infection. Pre-surgical induction of angiogenesis in tissues (preconditioning) limits ischemic complications and improves outcomes but very few preconditioning strategies have successfully been translated to clinical practice. The first goal of our research was to improve current standard of care in reconstructive surgery by developing a translational technique that can effectively and safely increase the vascularization of soft tissues. To achieve this goal, we optimized, using preclinical animal models resembling clinical needs and scenarios in a controlled setting, a method that adopts non-invasive external suction (External Volume Expansion, EVE) to precondition tissues through the induction of hypoxia-mediated angiogenesis. Using a sequential approach in a rodent model we determined the parameters of application (frequency, suction levels, duration, and interfaces) that fine-tune the balance of enhanced angiogenesis, attenuation of hypoxic tissue damage, and length of treatment. The optimized parameters of application (short, cyclical stimulations at moderate suction) almost doubled tissue vascular density after only 5 days of treatment. Our outcomes also showed that the use of micro-deformational interfaces of treatment retain the biological effectiveness of EVE while further reducing the cutaneous damage by distributing forces across the stimulated tissue. Our model confirmed that the optimized technique significantly improves the survival of transferred soft tissues (+20-30%), such as adipose tissue grafts, and can achieve the same beneficial outcomes in animal models of pathologic cutaneous vascularization, such as the one occurring in the skin of patients affected type-2 diabetes. We assessed that EVE retains a beneficial effect on the vascularization and proliferation (adipogenesis) of soft tissues when used both as a pre-conditioning method (before surgeries) and as a post-conditioning method (after surgeries) As a second goal of our research we integrated the knowledge on the application of EVE on soft tissues, to the use of a shelf-ready, bio-mimetic, decellularized allograft adipose matrix (AAM) with the aim of developing an innovative and minimally-invasive strategy for in vivo regeneration of soft tissues. In an animal model we tested the potential of a human-derived, injectable AAM to regenerate soft tissues when used in combination with EVE. This strategy significantly improved long-term volume retention (50-80% higher) and histological quality of reconstructed tissues compared to current standard of care (adipose grafts). The AAM induced both adipogenesis and angiogenesis. Combined use of the AAM and adipose grafts mitigated efficacy. Our studies suggest that EVE can improve the outcomes of reconstructive surgeries by safely and promptly enhance vascularity of soft tissues, in addition to its edema-/mechanically-induced adipogenic effect (confirmed by our study). EVE's use with an AAM, instead, can synergistically and effectively induce in vivo soft tissue regeneration. These translational principles are ready to be translated to clinical trials and, if outcomes will be confirmed, they could establish the basis for a novel therapeutic paradigm in reconstructive and regenerative surgery for the benefit of a large number of patients

    Reflections on a Decade of Face Transplantation

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    On November 27, 2005, Isabelle Dinoire underwent the world's first partial face transplant in Amiens (France) after a dog attack had left her face severely disfigured. The abrupt surgical leap found the medical community and society unprepared to deal with the scientific, ethical, and societal implications of a surgical procedure that was striving to transition from sci-fi novels to science. Today, 10 years and over 35 transplants later, public opinion has become accustomed to the concept of "face restoration" through transplantation. However, face transplantation is far from being a safe "routine" surgery and the science behind it is still mostly unknown. Patients and multidisciplinary teams of physicians confront daily medical challenges, life-threatening risks, and personal struggle that only in part come to light. Could (or should) this be the laborious, uncertain, and high-risk trajectory of disruptive medical innovation? Over the last decade, some medical discoveries and surgical advancements in the field have been closely accompanied by partial regulatory frameworks, intense ethical discussions, and meaningful changes in social beliefs across cultures and continents. Yet, a very long way is to come and the questions we still have today greatly outweigh the answers we can offer. Here, we take the chance of the 10-year anniversary of face transplantation to reflect on the path traveled and to look forward to the challenges lying ahead

    Reconstructive Strategies and Wound Management in Severe Pediatric Injuries of the Lower Limbs: Lessons From a Case Report

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    Abstract: Introduction. Severe injuries to lower limbs occurring in the pediatric population represent a unique challenge for reconstructive surgeons. The need for optimal anatomical repair and functional recovery must take into consideration several variables that may remarkably affect overall outcomes, length of hospitalization, and quality of life during recovery. The most appropriate therapeutic strategy should be based on the accurate planning of the least-invasive wound management, in terms of pain or other symptoms, local morbidity, and systemic response. Materials and Methods. With the purpose of discussing these issues, the authors present an illustrative case report of a 5-year-old child affected by a severe traumatic injury to the left leg complicated by wound hemorrhage as the result of a car accident. The vast loss of soft tissue was successfully treated by promptly staged surgical intervention and repair by using a regenerative dermal template. Results. Effective postoperative wound management and good compliance of the patient during hospitalization allowed for a substantial absence of complications and effective treatment of relevant symptoms. Conclusion. Excellent functional recovery at 12-month follow-up was achieved, as well as a good overall quality of life

    Advancements towards a functional amputation of the hand

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    The natural control of prosthetic robotic hands via surface electromyography (sEMG) remains a challenge despite the flexor-extensor muscular system of the fingers is usually partially preserved in patients with trans-radial amputations. In this work we analyze the Ninapro database (Non Invasive Adaptive Hand Prosthetics, http://ninapro.hevs.ch) which is currently the largest sEMG database of hand movements. The aim of the work is to identify relationships between clinical parameters of the amputation and movement recognition accuracy, in order to foster the integration between amputation surgery and innovative robotic hand prostheses
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