Fragmented Dermo-Epidermal Units (FdeU) as an Emerging Strategy to Improve Wound Healing Process: An In Vitro Evaluation and a Pilot Clinical Study.

Innovative strategies have shown beneficial effects in healing wound management involving, however, a time-consuming and arduous process in clinical contexts. Micro-fragmented skin tissue acts as a slow-released natural scaffold and continuously delivers growth factors, and much other modulatory information, into the microenvironment surrounding damaged wounds by a paracrine function on the resident cells which supports the regenerative process. In this study, in vitro and in vivo investigations were conducted to ascertain improved effectiveness and velocity of the wound healing process with the application of fragmented dermo-epidermal units (FdeU), acquired via a novel medical device (Hy-Tissue® Micrograft Technology). MTT test; LDH test; ELISA for growth factor investigation (IL) IL-2, IL-6, IL-7 IL-8, IL-10; IGF-1; adiponectin; Fibroblast Growth Factor (FGF); Vascular Endothelial Growth Factor (VEGF); and Tumor Necrosis Factor (TNF) were assessed. Therefore, clinical evaluation in 11 patients affected by Chronic Wounds (CW) and treated with FdeU were investigated. Functional outcome was assessed pre-operatory, 2 months after treatment (T0), and 6 months after treatment (T1) using the Wound Bed Score (WBS) and Vancouver Scar Scale (VSS). In this current study, we demonstrate the potential of resident cells to proliferate from the clusters of FdeU seeded in a monolayer that efficiently propagate the chronic wound. Furthermore, in this study we report how the discharge of trophic/reparative proteins are able to mediate the in vitro paracrine function of proliferation, migration, and contraction rate in fibroblasts and keratinocytes. Our investigations recommend FdeU as a favorable tool in wound healing, displaying in vitro growth-promoting potential to enhance current therapeutic mechanisms.

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.

Adipose micro-grafts enhance tendinopathy healing in ovine model: An in vivo experimental perspective study.

In Europe, approximatively 100 000 to 500 000 tendon repairs are performed every year. These procedures are associated with a considerable rate of postoperative complications (from 6% to 11%). Autologous micro-grafts (AAMG) and stromal vascular fraction (SVF) have been shown to improve tendon healing in 60% to 70% of treated rodents. The purpose of this study was to evaluate the effects of AAMG in a sheep model with tendinopathy. We used sheep models because, as a large animal, they are more comparable to humans. The hypothesis was that SVF injection would improve tendon healing compared with the control group, reducing inflammatory and matrix degrading, while increasing anti-inflammatory expression and collagen synthesis in the early stage of tendon injury. Sixteen Apennine sheep aged 2 to 5 years underwent 500 UI type I collagenase injection into both common calcaneal tendons (CCT) to induce tendinopathy. After 15 days (T0), one CCT in every ovine underwent randomly to 2.5 mL of AAMG obtained by mechanical disruption and the contralateral CCTs received no treatment. Clinical, ecographic, and sonographic evaluations were performed after 4 weeks (T1) and 8 weeks (T2). Histological, immunohistochemical, real-time polymerase chain reaction (RT-PCR), and biomechanical evaluations were performed at T2. At T2, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative-inflammatory process, and necrosis score (4.3 ± 3.3) compared with control group (8.8 ± 2.9). Immunohistochemically, the treated group showed high expression of collagen 1, Factor VIII and significantly low expression of collagen 3. These data were confirmed by RT-PCR analysis. The study findings suggested that AAMGs obtained through mechanical disruption present a safe, efficient, and reliable technique, enhancing tendon healing.

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.

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.

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.

Salvage of advanced carpal collapse: proximal row carpectomy with pyrocarbon resurfacing of the capitate versus four-corner arthrodesis.

In this retrospective study we report on two comparable groups of patients with advanced carpal arthritis treated with either proximal row carpectomy combined with a pyrocarbon resurfacing of the capitate (31 patients) or a four-corner arthrodesis and dorsal plating (26 patients). Follow-up time was 46 months (24-118). Except for a modestly higher radial wrist deviation in the patients treated with four-corner arthrodesis, there were no significant differences in outcomes between the groups. Asymptomatic progression of osteoarthritis in the lunate fossa was observed in four cases in both groups. Two cases were converted to a total wrist arthrodesis in the pyrocarbon group compared with one case in the four-corner arthrodesis group. Although four-corner arthrodesis remains the reference standard in the treatment of wrist osteoarthritis with involvement of the midcarpal joint, proximal row carpectomy combined with pyrocarbon resurfacing of the capitate is an alternative option. It can even be used in selected cases with erosion of the lunate fossa.Level of evidence: III.

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.

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.

Mechanical and Enzymatic Procedures to Isolate the Stromal Vascular Fraction From Adipose Tissue: Preliminary Results.

Adipose-derived MSCs (ASCs) and stromal vascular fraction (SVF) play an important role in regenerative medicine and in the treatment of osteoarthritis. ASCs extracted from lipoaspirates are a valuable cell source due to their abundance and accessibility. ASCs are retrieved from the aqueous fraction of the digested lipoaspirate. The aqueous fraction is known as SVF and includes, ASCs, endothelial precursor cells (EPCs), endothelial cells (ECs), macrophages, smooth muscle cells, lymphocytes, pericytes, as well as pre-adipocytes. To date, two types of techniques to isolate SVF have been proposed: enzymatic and mechanical. The enzymatic method is particularly indicated in SVF isolation since it disrupts the extracellular matrix (ECM) and the binding of adipocytes and other cells but is restricted by regulatory issues related to enzymatic procedures, especially within the European Community. Thus, making the search for alternative mechanical methods imperative. This study assesses the SVF harvested from subcutaneous abdominal fat via two different mechanical procedures and the standard enzymatic method to evaluate their eligibility in a clinical context. In particular, we analyze cell viability (at 0 and after 72 h) as well as the expression of cluster differentiation (CD) for each sample and the differentiation in adipocytic, chondrocytic, osteocytic linage. The mechanical procedures yielded no significant difference in cell viability and cluster differentiation pattern expression, even if enzymatic procedure still remain the "gold standard." We retain that clinical efficacy in treating ostheoarthrosis with SVF administration is probably related to his anti-inflammatory and immunoregulatory effect, rather than the ability to differentiate in specific cell lineage. However, further studies are required to support and improve our findings.

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 .