Efficacy of Adipose-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction Alone and Combined to Biomaterials in Tendinopathy or Tendon Injury: Systematic Review of Current Concepts.

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.

K-wire fixation vs 23-gauge percutaneous hand- crossed hypodermic needle for the treatment of distal phalangeal fractures.

BACKGROUND: Distal Phalanx (DP) fractures are the most common hand injuries. Bone fixation associated with soft tissue reconstruction, is often required to ensure more effective outcomes. The aim of the present study is to compare functional outcomes of DP fractures surgically treated with crossed manual drilled 23 Gauge needles vs crossed Kirschner-wires (k-wire). METHODS: Clinical data included analysis of patient demographics, range of motion (ROM), and complications. Radiographic assessment considered fracture type, location, fracture displacement, and radiographic union. Functional outcomes analysis was performed.The statistical significance was assessed at the level of probability lower than 5%. RESULTS: A total of 60 patients from 2012 to 2015 were retrospectively enrolled and among them 12 patients suffering from diabetes or current smokers. A total of 60 DP fractures were treated, 32 with needles (group A) and 28 with k-wire fixation (group B). Time to union, showed in different time points, was significantly lower in group A (≤ 40 days, p = 0.023*) compared to group B. ROM of the distal interphalangeal joint at six months follow-up was 60° in group A and 40° in group B. A significant improvement was observed (p = 0.001*) in the 23 G needle treated group. Functional outcome analysis showed that VAS was significantly lower in group A compared to group B (p = 0.023*). CONCLUSION: Our study showed that the 23 G needle yielded satisfactory results in terms of time to union and range of motion compared to k-wire fixation especially for tuft and shaft DP fractures. Therefore, should be a valid alternative to k-wire fixation in selected patients.

A Multistep Iter for Functional Reconstruction in Mangled Upper Limb: A Retrospective Analysis of Integrated Surgical and Medical Approach.

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.

Efficacy of the Arteriovenous Loop for Free Flap Reconstruction in Patients with Complex Limb Trauma: Case Series and Literature Review.

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.

Nerve repair and regeneration: Biological tubulization limits and future perspectives.

Peripheral nerve physiology and regeneration has been observed and investigated in literature but surgical applications to reconstruct and restore motor or sensory functions are still in a developmental phase. The peripheral nerve progresses slowly and incompletely compared with other tissues, it may provoke separations of the nerve stumps and the axonal proliferation of the conduits is restricted to 30 mm. Recent surgical attempts to treat proximal nerve injures include direct nerve restoration, transfer, and autografting measures with favorable results. Moreover, studies are suggesting that engineering tissue tubes maybe as effective as nerve grafting to restore separations of more than 4 cm toward optimal nerve repair.

Managing Pathologic Scars by Injecting Auto-Cross-linked Hyaluronic Acid: A Preliminary Prospective Clinical Study.

BACKGROUND: Pathological scars are unattractive and may significantly impair the patient's quality of life. Current treatments provide inconsistent results, and none may be regarded as definitive. Recently, an auto-cross-linked hyaluronic acid (HA) formulation, IAL-SYSTEM ACP, featuring a long residence time and an enhanced safety profile, has been successfully used to prevent surgical adhesions, treat tendon lesions and rejuvenate the face and the décolletage. This study aims to preliminarily investigate whether IAL-SYSTEM ACP may also be effective in treating pathological scars resulting from burns, trauma or iatrogenic causes. METHODS: Patients presenting one pathological scar were prospectively recruited and treated with two IAL-SYSTEM ACP injections carried out two weeks apart. Scar improvement was measured comparing the patient and observer scar assessment scale (POSAS) scores collected before treatment (T0) and 90 days after the second injection (T90) using nonparametric tests. The effect of age and scar type over score variation was investigated through quantile regression analysis. RESULTS: Forty-one patients, 10 women and 31 men (median age, 34 years) were recruited. No patient dropped out, and no significant adverse event was observed. At T90, the median observer total score decreased by 11 units (- 77.5%) and the median patient total score decreased by 15 units (- 73.7%). The difference was significant (p < 0.001) in both cases. Traumatic injuries and young patient's age were the most significant predictors of a positive treatment outcome. CONCLUSIONS: Treatment of pathological scars by two IAL-SYSTEM ACP injections, carried out two weeks apart, may provide significant clinical benefits. These findings should be the subject of further investigations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The amnion muscle combined graft (AMCG) conduits in nerves repair: an anatomical and experimental study on a rat model.

The amnion muscle combined graft (AMCG) conduits showed good clinical results in peripheral nerves gap repair. It combines the human amniotic membrane with autologous skeletal muscle fibres. These results seem attributable to the biological characteristics of human amniotic membrane: Pluripotency, anti-inflammatory and low immunogenicity.We here evaluate the final outcome of nerve regeneration morphologically and functionally, across the AMCG compared to nerve autograft. Fourteen Wistar rats were divided into two groups: In Group A, including 6 rats, the left forelimb was treated performing a 1.5 cm length gap on median nerve that was then reconstructed with a reverse autograft. In Group B, including 8 rats, the gap was reconstructed with AMCG. Functional results were evaluated at 30, 60 and 90 days performing grasping tests. Morphological and stereological analyses were performed at T90 using high-resolution light microscopy and design-based stereology. The AMCG conduits revealed nerve fibres regeneration and functional recovery. Functional recovery was observed in both groups with AMCG conduits group showing lower values and a regeneration of median nerves with more myelinated fibres with the same axon size, but thinner myelin than the autograft group. Though the autograft remains the gold standard to restore wide nerve gaps, the AMCG conduit has proved to be effective in enabling nerve regeneration through a critical rat's nerve gap of 15 mm. These findings empirically support the great clinical results obtained using AMCG conduit to restore traumatic nerve's gap from 3 to 6 cm of mixed forearm nerves.

The amnion muscle combined graft (AMCG) conduits: a new alternative in the repair of wide substance loss of peripheral nerves.

The use of autologous sural nerve grafts is still the current gold standard for the repair of peripheral nerve injuries with wide substance losses, but with a poor rate of functional recovery after repair of mixed and motor nerves, a limited donor nerve supply, and morbidity of donor site. At present, tubulization through the muscle vein combined graft, is a viable alternative to the nerve autografts and certainly is a matter of tissue engineering still open to continuous development, although this technique is currently limited to a critical gap of 3 cm with less favorable results for motor function recovery. In this report, we present a completely new tubulization method, the amnion muscle combined graft (AMCG) technique, that consists in the combination of the human amniotic membrane hollow conduit with autologous skeletal muscle fragments for repairing the substance loss of peripheral nerves and recover both sensory and motor functions. In a series of five patients with loss of substance of the median nerve ranging 3-5 cm at the wrist, excellent results graded as S4 in two cases, S3+ in two cases, and S3 in one case; M4 in four cases and M3 in one case were achieved. No iatrogenic damage due to withdrawal of a healthy nerve from donor site was observed. This technique allows to repair extensive loss of substance up to 5 cm with a good sensory and motor recovery. The AMCG thus may be considered a reasonable alternative to traditional nerve autograft in selected clinical conditions.

A case report of upper limb loss of substance: Use of functional gracilis free flap, brachioradialis transposition and bioglass for bone regeneration.

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.

A Peculiar Case of Open Complex Elbow Injury with Critical Bone Loss, Triceps Reinsertion, and Scar Tissue might Provide for Elbow Stability?

BACKGROUND: Complex elbow injuries (CEIs) are severe and rare lesions, difficult to treat correctly due to the different patterns of clinical presentations. Standard methods cannot often be applied. The main goals of the treatment are performing a stable osteosynthesis of all fractures, obtaining a concentric and stable reduction of the elbow by repairing the soft tissue constraint lesions, and allowing early motion. Since the introduction of virtual reality (VR) approaches in clinical practice, three-dimensional (3D) computed tomography (CT) and 3D printing have revolutionised orthopaedic surgeries, thus helping to understand the anatomy and the pathology of complex cases. CASE DESCRIPTION: We discussed a case of CEI, characterised by an extended soft tissue (IIIB Gustilo classification) and neurovascular lesions associated with bone loss in a young female patient. Olecranon fracture was type IIIB according to Mayo classification. We outlined the steps of a pluri-tissue reconstructive approach and stressed the importance of 3D printing in the preoperative planning for such cases. Finally, peculiar final functional patient outcomes were reported. CONCLUSION: In this case, we found out that triceps reinsertion and scar process may provide for the joint stability in a low-demanding patient. 3D printing and VR approaches in clinical practice can be useful in the management of CEIs associated with an important bone and soft tissue loss. HOW TO CITE THIS ARTICLE: Facco G, Politano R, Marchesini A, et al. A Peculiar Case of Open Complex Elbow Injury with Critical Bone Loss, Triceps Reinsertion, and Scar Tissue might Provide for Elbow Stability? Strategies Trauma Limb Reconstr 2021;16(1):53-59.

A New Animal Model for Pathological Subcutaneous Fibrosis: Surgical Technique and in vitro Analysis.

Fibrosis is a condition that affects the connective tissue in an organ or tissue in the restorative or responsive phase as a result of injury. The consequences of excessive fibrotic tissue growth may lead to various physiological complications of deformity and impairment due to hypertrophic scars, keloids, and tendon adhesion without understating the psychological impact on the patient. However, no method accurately quantifies the rate and pattern of subcutaneous induced hypertrophic fibrosis. We, therefore, devised a rodent excisional model to evaluate the extent of fibrosis with talc. Tissue specimens were set on formalin, and paraffin sections for histological, immunohistochemical, and molecular analysis talc was used to induce the fibroproliferative mechanism typical of hypertrophic scars. This pathway is relevant to the activation of inflammatory and fibrotic agents to stimulate human hypertrophic scarring. This model reproduces morpho-functional features of human hypertrophic scars to investigate scar formation and assess potential anti-scarring therapies.

Functional donor-site morbidity after soleus muscle-flap procedure in the treatment of lower limb severe injuries.

BACKGROUND: The gastrocnemius and soleus muscle flaps are the most commonly used transfer flaps to treat lower limb severe lesions. The use of the muscle as coverage tissuemay incur in functionality loss and motor control deficits. The aim of this study is to assess whether functional deficits are present during gait, posture and heel rise test (HRT). METHOD: From 2008-2013 we treated 9 patients suffering from complex injury of the lower third of the leg (Gustilo III B). A population of 9 patients (group A) was examined after reconstruction with a soleus muscle flap. The results were compared with a control population (group B: 9 patients). Each patient performed at least 3 gait tests at a fast pace, 2 posture tests and 2 HRT on an inclined plane. RESULTS: Gait parameters for group A: Spatio-temporal parameters such as step length, cadence were reduced compared to the homolateral leg (p < 0.05). The initial double support phase was shorter in relation to the final phase and the first peak in the vertical ground reaction component was reduced compared to the contralateral leg.Posture for the group A: the mediolateral excursion (during open- and closed-eyes test) and the related mean velocity (in the open-eyes test) were significantly lower compared to the control group (p < 0.05).HRT for group A: the number of rises and relative height and angular excursion were reduced in the operated leg in relation to the control group (p < 0.05) and to the contralateral leg. CONCLUSION: The patients treated with the soleus muscle used as tissue defect coverage completely recovered the ability to walk but showed some deficits in kinetic parameters during the body weight-loading phase. During gait prolonged muscle activity compared to controls was observed. The absence of soleus (group A) revealed no significant alterations in postural control. However, the HRT remained the most relevant test to measure patients' performance when treated with soleus flap in relation to the control group.

A Rare Case of Distal Interphalangeal Chondromatosis in the Middle Finger: Case Report With Review of Literature.

Primary synovial chondromatosis is a benign condition and consists of cartilaginous metaplasia of the synovium, which leads to the production of intra-articular and periarticular osteocartilaginous bodies. The entity usually involves the synovium of large joints (knee, hip, elbow, and shoulder). It has also been reported in the hand, especially involving interphalangeal or metacarpal joints of digits. The most common symptoms are pain, swelling, loss of range of motion and muscle atrophy. Because of its low prevalence and non-specific symptoms, synovial chondromatosis can present a diagnostic challenge for the hand surgeon and may lead to a delay in treatment. To date, only three cases involving distal interphalangeal joint have been reported. This article describes a rare case of primary articular synovial chondromatosis in the distal interphalangeal joint of a 65-year-old female, giving a deep insight into this pathology, and reviews the literature.

A Multicentre Study: The Use of Micrografts in the Reconstruction of Full-Thickness Posttraumatic Skin Defects of the Limbs-A Whole Innovative Concept in Regenerative Surgery.

The skin graft is a surgical technique commonly used in the reconstructive surgery of the limbs, in order to repair skin loss, as well as to repair the donor area of the flaps and cover the dermal substitutes after engraftment. The unavoidable side effect of this technique consists of unaesthetic scars. In order to achieve the healing of posttraumatic ulcers by means of tissue regeneration and to avoid excessive scarring, a new innovative technology based on the application of autologous micrografts, obtained by Rigenera technology, was reported. This technology was able to induce tissue repair by highly viable skin micrografts of 80 micron size achieved by a mechanical disaggregation method. The specific cell population of these micrografts includes progenitor cells, which in association with the fragment of the Extracellular Matrix (ECM) and growth factors derived by patients' own tissue initiate biological processes of regeneration enhancing the wound healing process. We have used this technique in 70 cases of traumatic wounds of the lower and upper limbs, characterized by extensive loss of skin substance and soft tissue. In all cases, we have applied the Rigenera protocol using skin micrografts, achieving in 69 cases the complete healing of wounds in a period between 35 and 84 days. For each patient, the reconstructive outcome was evaluated weekly to assess the efficacy of this technique and any arising complication. A visual analogue scale (VAS) was administered to assess the amount of pain felt after the micrografts' application, whereas we evaluated the scars according to the Vancouver scale and the wound prognosis according to Wound Bed Score. We have thus been able to demonstrate that Rigenera procedure is very effective in stimulating skin regeneration, while reducing the outcome scar.

Assessment of functional outcomes of temporalis muscle transfers for patients with longstanding facial paralysis.

BACKGROUND: Usually, clinical evaluation of facial reanimation provides accurate information about contraction of the mimetic muscles and phonation but fails to identify smile recovery and to quantify the motility of the lower third of the face during a smile. The purpose of this study was to verify that, in longstanding facial palsy, the modified temporalis muscle transfer (MTMT) can result in the ability to smile, not only voluntarily with chewing, but also spontaneously with a sudden emotional stimulus, and to confirm that a symmetric smile can be obtained. METHODS: Ten patients of the treated group (group T; 4 women and 6 men) were randomly selected from a population of 24 patients with longstanding facial palsy treated by MTMT. Five normal subjects of the control group (group C; 3 women and 2 men) were enrolled as the control population. Functional outcomes after transposed temporalis muscle were examined and measured through clinical assessment by using a scored smile symmetry grading system, video recording, and surface electromyography (sEMG). In addition, the voluntary smile test (VST) and the not-voluntary smile test (NVST) were performed to study voluntary and spontaneous smiling. RESULTS: Subjects in the VST group (group T) were able to smile voluntarily and the expression was characterized by symmetry. In the NVST group, they were able to smile spontaneously and the symmetry of the smile was maintained for 8 subjects and only partially for 2 subjects. During both tests, the temporalis muscle of the treated side and the orbicularis oris muscle of the not-treated side were activated during smiling, indicating spontaneous activity of the transposed temporalis muscle with an emotional stimulus. For the control group, smiles during VST and NVST were symmetric and the temporalis muscles were not activated during smiling, whereas the orbicularis oris muscles were. CONCLUSION: Our study shows that the Morrison MTMT is able to restore the voluntary smile ability. Particularly, this technique allows for recovery of the spontaneous smile with symmetry. This assessment would seem to suggest that the transposed temporalis muscle might adapt from a chewing to a mimetic muscle. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1535-E1543, 2016.

Tissue Characterization after a New Disaggregation Method for Skin Micro-Grafts Generation.

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.