Background and objectives: Complex limb traumas are commonly treated with microsurgical reconstruction and free flaps. However, complications are frequent in patients affected by a previous trauma or comorbidity, atheromasia and a single valid vessel. Free flap reconstruction is indeed a challenging procedure in complex injuries, which may increase the risk of limb ischemia. The Arteriovenous loop (AVL) technique may be considered an efficient alternative treatment. We herein report our procedure and previous research regarding the AVL method using a two-step reconstruction in cases of complex high-energy limb injuries. Materials and Methods: In this single center retrospective cohort study, all the patients from 2014 to 2018 who underwent to AVL reconstruction were assessed. A total of six patients were included in the study for traumatic limb trauma. The two-stage technique was performed each time. The age and sex of patient, the time between stage one and two, the length of AVL loop and rate of free flap success were evaluated. Results: A total of seven AVL reconstructions were performed. The mean age of patients was 36 years old. Eight free flaps were performed; six free flaps were transferred to the vascular loops. The average time between stage one and two was 13 days. The mean length of the pedicle was 25 cm for the upper limb and 33.7 cm for the lower limb. All the free flaps successfully take root. In one case, a surgical revision was required the second day post-operatory due to venous congestion. Conclusions: AVL is a useful and safe technique in microsurgical reconstruction which will prevent vascular complications. Our investigations suggest the efficacy and feasibility of a two-step intervention in acute post-traumatic events. A single-step procedure should be preferred in chronic situation and oncologic reconstruction.

Background and Objectives: Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. Materials and Methods: This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Conclusions: Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications.

Background and objectives: Complex limb wounds with multiple tissue involvement are commonly due to high energy trauma. Tissue damage is a dynamic entity and the exact extent of the injury is rarely instantly perceptible. Hence, reconstruction frequently involves a multi-stage procedure concluding with tissue replacement. Materials and Methods: A retrospective study was conducted between 2006 and 2018 and included 179 patients with contaminated multi-tissue injuries treated with hyperbaric oxygen therapy, negative pressure therapy, physiotherapy and drug treatment associated with multiple surgical time in a multistep approach, focusing on pain levels and wound closure rates. Results: Despite the long-term response to traumatic events, a combined approach of delayed surgical reconstructive time in mangled upper limb yielded satisfactory functional outcomes. Conclusions: The complex upper limb wound with deep tissue exposure may be treated with a multi-stage procedure alternatively to immediate reconstruction. The integrated technique enables the preservation of existing healthy tissue and concurrent radical debridement, reducing the risk of infection, as well as avoiding the loss of free flaps and dehiscence due to incorrect wound estimation.

Complex trauma of the upper limb is a common consequence of involvement in serious accidents. Loss of substance including nerve, bone, tendons and vascular defects are challenging surgical issues. A 27- year-old male presented with complex upper limb trauma and loss of a proximal third of the posterior forearm structure as well as loss of active finger extension, ulnar and radial nerve territory anesthesia and ulnar fracture. A composite nerve-tendon-muscle-skin gracilis free flap was retrieved from the contralateral leg, related to tendon transfer of BR to ELP, to supply active hand extension. The patient was required to adhere to intensive post-surgical rehabilitation and monitored for a 3-year follow-up period. Our assessment revealed adequate skin trophism and sufficient muscle strength recovery against resistance (M5). The functional flap associated with tendon transfer was considered an efficient procedure for the management of a complex trauma with loss of posterior interosseous nerve and bone exposition. The free re-innervated gracilis flap may be used to repair complex soft tissue defects with exposed bone and to restore finger extension following severe forearm injuries.

Several new methods have been developed in the field of biotechnology to obtain autologous cellular suspensions during surgery, in order to provide one step treatments for acute and chronic skin lesions. Moreover, the management of chronic but also acute wounds resulting from trauma, diabetes, infections and other causes, remains challenging. In this study we describe a new method to create autologous micro-grafts from cutaneous tissue of a single patient and their clinical application. Moreover, in vitro biological characterization of cutaneous tissue derived from skin, de-epidermized dermis (Ded) and dermis of multi-organ and/or multi-tissue donors was also performed. All tissues were disaggregated by this new protocol, allowing us to obtain viable micro-grafts. In particular, we reported that this innovative protocol is able to create bio-complexes composed by autologous micro-grafts and collagen sponges ready to be applied on skin lesions. The clinical application of autologous bio-complexes on a leg lesion was also reported, showing an improvement of both re-epitalization process and softness of the lesion. Additionally, our in vitro model showed that cell viability after mechanical disaggregation with this system is maintained over time for up to seven (7) days of culture. We also observed, by flow cytometry analysis, that the pool of cells obtained from disaggregation is composed of several cell types, including mesenchymal stem cells, that exert a key role in the processes of tissue regeneration and repair, for their high regenerative potential. Finally, we demonstrated in vitro that this procedure maintains the sterility of micro-grafts when cultured in Agar dishes. In summary, we conclude that this new regenerative approach can be a promising tool for clinicians to obtain in one step viable, sterile and ready to use micro-grafts that can be applied alone or in combination with most common biological scaffolds.

Peritendinous adhesions are a frequent occurrence following tenolysis and present a major clinical challenge regarding prevention and management, with no recovery assured from conservative or surgical approaches. Herein, we investigated the effectiveness of Hyaloglide^®, a hyaluronan gel-based product with a novel autocross-linked technology, in a rabbit model affected by tenolysis on the flexor digitorum communis tendon (FDC). A 1.5-cm-long scrubbing of the tendon surface was performed bilaterally to induce peritendinous adhesion on FDC of 30 animals with subsequent application of Hyaloglide^® on the surrounding injured area, in one randomly chosen tendon. The contralateral tendon was treated with saline solution as the control. We sacrificed the rabbit models after 45 days of surgery and quantitatively assessed the generation of peritendinous adherence and regeneration of the tendon sheaths using histological (hematossyline-eosine, masson’s trichromic), histomorphometrical (Tang score, Soslowsky Svesson, and Cook score), light electron microscopic, and gene expression investigations. Four rabbits were devoted to biomechanical analysis. Peritendinous adhesions were limited in Hyaloglide^®-treated tendons; moreover, well-regenerated tendon sheaths were observed conversely to untreated tendons presenting with extensive areas of adhesions on the tendon surface. Histomorphometrical analysis revealed an adhesion score (Tang score) significantly better in the treated group (p = 0.001 *) compared to the control group. Moreover, the Soslowsky, Svensson, and Cook score parameters revealed a significantly improved regeneration for fiber structure, cellularity, and vascularity in the treated group (p = 0.001 *). No differences were reported for cartilaginous formation (p = 0.08). Gene expression analysis showed a significant increase in collagen type I expression in the treated group compared to the control group, while metalloprotease 1 and 9 were significantly increased in the control group. Biomechanical analysis did not show significant differences in both groups. Hyaloglide^® treatment was safe and well-tolerated, generating improved tissue status. Local application of Hyaloglide^® prevents adhesion formation after tenolysis and promotes normal healing with regeneration of the synovial sheath in a rabbit model.