Robotic Microsurgery in Extremity Reconstruction - Experience With a Novel Robotic System.

Background: Robotic systems have successfully been introduced into other surgical fields in the past. First attempts with different setups are made in the field of microsurgery. The Symani® Surgical System, a flexible platform consisting of two robotic arms, features motion scaling with tremor filtration to address the demands and complexity of microsurgery. Symani's NanoWrist Instruments are the world's smallest, wristed surgical instruments, intended to improve a surgeon's range of motion beyond the capability of the human hand. This combination allows surgeons to scale their hand movements while seamlessly articulating the robotic micro instruments. Purpose: We report on our experience in extremity reconstruction with this novel system.Research Design: The Symani Surgical System® was used for 6 cases of extremity reconstruction. The surgeon controlled the manipulators along with the footswitch while either sitting away from the operating table relying on 3D visualization with an exoscope or sitting at the operating table using a standard microscope.Data Collection: Microsurgical anastomoses were performed in 4 patients (3 end-to-end arterial anastomoses and one end-to-side arterial anastomosis) and nerve grafting was performed in 2 patients.Results: Microvascular anastomoses were slower vs conventional microsurgery, but all anastomoses were patent. Epineural coaptation showed proper fascicle alignment and tissue manipulation could be kept to a minimum. The platform's motion scaling allows the surgeon to perform precise micro-movements with only minimal tissue manipulation and hard-to-reach anatomy becomes accessible more easily.Conclusions: Robotic microsurgery might gain importance in the nearer future but more data will need to be collected.

Adipose-derived stem cells applied in skin diseases, wound healing and skin defects: a review.

Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells.

Distraction Arthroplasty for Basal Thumb Osteoarthritis: 10-Year Follow-Up.

PURPOSE: Trapeziectomy has frequently been used to treat basal thumb osteoarthritis. However, complications, such as shortening of the thumb ray and reduced mobility and strength, can occur. The aim of this study was to present a 10-year follow-up of distraction arthroplasty without trapeziectomy. METHODS: Fifteen patients were followed for a mean of 121 months (range, 121-124 months). Subjective outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire, while the pain intensity was assessed with a Visual Analog Scale both before surgery and at the end of follow-up. Objective outcomes were obtained using the Kapandji score and an assessment of grip and pinch strength. Preoperative and final postoperative x-rays were obtained to evaluate metacarpal subsidence and progression of trapezial-metacarpal joint arthritis. RESULTS: The Visual Analog Scale score was reduced from 9.4 ± 0.5 before surgery to 2.5 ± 1 at follow-up. The mean Disabilities of the Arm, Shoulder, and Hand questionnaire score was 75.6 ± 12.6 before surgery and 16.9 ± 4 at 10 years. Hand grip strength of the operated side (26 ± 5.5 kg) achieved 95% of functionality compared to the opposite side, while key pinch strength (6.4 ± 1.6 kg) reached 93%. A Kapandji opposition score of 10 points was found in 12 patients, a score of 9 was found in 1, and a score of 8 was found in 2. CONCLUSIONS: Distraction arthroplasty of the trapeziometacarpal joint ensures good results in long-term follow-up, when performed in patients with stage I-II basal thumb osteoarthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

In Vitro and In Vivo Effects of IGF-1 Delivery Strategies on Tendon Healing: A Review.

Tendon injuries suffer from a slow healing, often ending up in fibrovascular scar formation, leading to inferior mechanical properties and even re-rupture upon resumption of daily work or sports. Strategies including the application of growth factors have been under view for decades. Insulin-like growth factor-1 (IGF-1) is one of the used growth factors and has been applied to tenocyte in vitro cultures as well as in animal preclinical models and to human patients due to its anabolic and matrix stimulating effects. In this narrative review, we cover the current literature on IGF-1, its mechanism of action, in vitro cell cultures (tenocytes and mesenchymal stem cells), as well as in vivo experiments. We conclude from this overview that IGF-1 is a potent stimulus for improving tendon healing due to its inherent support of cell proliferation, DNA and matrix synthesis, particularly collagen I, which is the main component of tendon tissue. Nevertheless, more in vivo studies have to be performed in order to pave the way for an IGF-1 application in orthopedic clinics.

Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair.

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier.

A Cohort Study on Neuropathic Pain of the Sural Nerve-Can Neurectomy Be Considered a Valid Treatment Option?

BACKGROUND: Sural nerve neuroma is often caused by an injury during prior surgery, for example, osteosynthesis or ligament refixations at ankle level. Different surgical techniques to treat neuroma have been described. Neurectomy of an injured symptomatic sural nerve has been described as a treatment option for neuropathic pain. The aim of this study was to evaluate the outcomes of this technique to operatively treat sural nerve neuroma in our department. METHODS: From 2010 to 2020, a total of 30 consecutive patients with neuropathic pain and suspected neuroma of the sural nerve underwent sural nerve neurectomy. A medical chart review was performed to collect patient-, pain-, and treatment-specific factors. Outcomes were registered. RESULTS: After neurectomy, 22 patients (73.3%) had persisting pain. In logistic regression models evaluating the risk of persisting pain after sural nerve neurectomy, no independent predictor of higher risk of persisting pain could be identified. CONCLUSION: For sural nerve neuromas, neurectomy remains an option as the surgical morbidity is minor, but patients need to be counseled that only a fourth of those undergoing surgery will be pain-free afterward.

Impact of High-Molecular-Weight Hyaluronic Acid on Gene Expression in Rabbit Achilles Tenocytes In Vitro.

(1) Background: Surgical tendon repair often leads to adhesion formation, leading to joint stiffness and a reduced range of motion. Tubular implants set around sutured tendons might help to reduce peritendinous adhesions. The lubricant hyaluronic acid (HA) is a viable option for optimizing such tubes with the goal of further enhancing the anti-adhesive effect. As the implant degrades over time and diffusion is presumed, the impact of HA on tendon cells is important to know. (2) Methods: A culture medium of rabbit Achilles tenocytes was supplemented with high-molecular-weight (HMW) HA and the growth curves of the cells were assessed. Additionally, after 3, 7 and 14 days, the gene expression of several markers was analyzed for matrix assembly, tendon differentiation, fibrosis, proliferation, matrix remodeling, pro-inflammation and resolution. (3) Results: The addition of HA decreased matrix marker genes, downregulated the fibrosis marker α-SMA for a short time and slightly increased the matrix-remodeling gene MMP-2. Of the pro-inflammatory marker genes, only IL-6 was significantly upregulated. IL-6 has to be kept in check, although IL-6 is also needed for a proper initial inflammation and efficient resolution. (4) Conclusions: The observed effects in vitro support the intended anti-adhesion effect and therefore, the use of HMW HA is promising as a biodegradable implant for tendon repair.

Retrograde Free Venous Flaps for Extremity Reconstruction: A Roadmap.

Background and Objectives: Retrograde free venous flaps represent a separate entity among free venous flaps: their physiology is still unclear, but they provide an immediate visible refill after reconnection, with a similar behaviour to conventional flaps. Therefore, the dimensions and the indications of these flaps can be extended beyond what was previously believed, and they can be easily customized, including with respect to tendons and nerves. Nevertheless, they are still debated and regarded as unsafe. Materials and Methods: From 2012 to 2019, we performed 31 retrograde free venous flaps on 31 patients to reconstruct hands, digits, and in one case the heel. All the flaps were arterialized in a retrograde manner; the donor site was the forearm in 28 cases, the foot in 2 cases, and the calf in 1 case. We recorded the size, vein architecture, donor site, donor artery, donor morbidity, function for composite and non-composite flaps, immediate complications, late complications, survival rate, and the number of revisions. We recorded the hand function when appropriate. A total of 10 flaps were also intraoperatively studied with indocyanine green to monitor their hemodynamical behaviour. Results: All the patients were followed for an average of 8 months (6−15). The flap dimensions ranged from 6 cm2 to 136 cm2. All the flaps, except two that had complete necrosis, survived. Two flaps had partial necrosis. There was no correlation between necrosis and the size of the flap, with one case of necrosis and one of partial necrosis in the small flaps (<10 cm2). None of the cases with partial necrosis needed a new flap. Two flaps developed a late arterio-venous shunt that was ligated. Conclusions: The retrograde free venous flaps proved to be a useful tool for complex reconstructions of the hand and extremities. They can provide a large island of pliable skin and composite tissue with tendons and nerves, but surgeons must be aware of some caveats.

Thermal conditioning improves quality and speed of keratinocyte sheet production for burn wound treatment.

BACKGROUND AIMS: Cultured patient-specific keratinocyte sheets have been used clinically since the 1970s for the treatment of large severe burns. However, despite significant developments in recent years, successful and sustainable treatment is still a challenge. Reliable, high-quality grafts with faster availability and a flexible time window for transplantation are required to improve clinical outcomes. METHODS: Keratinocytes are usually grown in vitro at 37°C. Given the large temperature differences in native skin tissue, the aim of the authors' study was to investigate thermal conditioning of keratinocyte sheet production. Therefore, the influence of 31°C, 33°C and 37°C on cell expansion and differentiation in terms of proliferation and sheet formation efficacy was investigated. In addition, the thermal effect on the biological status and thus the quality of the graft was assessed on the basis of the release of wound healing-related biofactors in various stages of graft development. RESULTS: The authors demonstrated that temperature is a decisive factor in the production of human keratinocyte sheets. By using specific temperature ranges, the authors have succeeded in optimizing the individual manufacturing steps. During the cell expansion phase, cultivation at 37°C was most effective. After 6 days of culture at 37°C, three times and six times higher numbers of viable cells were obtained compared with 33°C and 31°C. During the cell differentiation and sheet formation phase, however, the cells benefited from a mildly hypothermic temperature of 33°C. Keratinocytes showed increased differentiation potential and formed better epidermal structures, which led to faster biomechanical sheet stability at day 18. In addition, a cultivation temperature of 33°C resulted in a longer lasting and higher secretion of the investigated immunomodulatory, anti-inflammatory, angiogenic and pro-inflammatory biofactors. CONCLUSIONS: These results show that by using specific temperature ranges, it is possible to accelerate the large-scale production of cultivated keratinocyte sheets while at the same time improving quality. Cultivated keratinocyte sheets are available as early as 18 days post-biopsy and at any time for 7 days thereafter, which increases the flexibility of the process for surgeons and patients alike. These findings will help to provide better clinical outcomes, with an increased take rate in severe burn patients.

In Vivo Measurement of Wrist Movements during the Dart-Throwing Motion Using Inertial Measurement Units.

BACKGROUND: This study investigates the dart-throwing motion (DTM) by comparing an inertial measurement unit-based system previously validated for basic motion tasks with an optoelectronic motion capture system. The DTM is interesting as wrist movement during many activities of daily living occur in this movement plane, but the complex movement is difficult to assess clinically. METHODS: Ten healthy subjects were recorded while performing the DTM with their right wrist using inertial sensors and skin markers. Maximum range of motion obtained by the different systems and the mean absolute difference were calculated. RESULTS: In the flexion-extension plane, both systems calculated a range of motion of 100° with mean absolute differences of 8°, while in the radial-ulnar deviation plane, a mean absolute difference of 17° and range of motion values of 48° for the optoelectronic system and 59° for the inertial measurement units were found. CONCLUSIONS: This study shows the challenge of comparing results of different kinematic motion capture systems for complex movements while also highlighting inertial measurement units as promising for future clinical application in dynamic and coupled wrist movements. Possible sources of error and solutions are discussed.

Adipose tissue and the vascularization of biomaterials: Stem cells, microvascular fragments and nanofat-a review.

Tissue defects in the human body after trauma and injury require precise reconstruction to regain function. Hence, there is a great demand for clinically translatable approaches with materials that are both biocompatible and biodegradable. They should also be able to adequately integrate within the tissue through sufficient vascularization. Adipose tissue is abundant and easily accessible. It is a valuable tissue source in regenerative medicine and tissue engineering, especially with regard to its angiogenic potential. Derivatives of adipose tissue, such as microfat, nanofat, microvascular fragments, stromal vascular fraction and stem cells, are commonly used in research, but also clinically to enhance the vascularization of implants and grafts at defect sites. In plastic surgery, adipose tissue is harvested via liposuction and can be manipulated in three ways (macro-, micro- and nanofat) in the operating room, depending on its ultimate use. Whereas macro- and microfat are used as a filling material for soft tissue injuries, nanofat is an injectable viscous extract that primarily induces tissue remodeling because it is rich in growth factors and stem cells. In contrast to microfat that adds volume to a defect site, nanofat has the potential to be easily combined with scaffold materials due to its liquid and homogenous consistency and is particularly attractive for blood vessel formation. The same is true for microvascular fragments that are easily isolated from adipose tissue through collagenase digestion. In preclinical animal models, it has been convincingly shown that these vascular fragments inosculate with host vessels and subsequently accelerate scaffold perfusion and host tissue integration. Adipose tissue is also an ideal source of stem cells. It yields larger quantities of cells than any other source and is easier to access for both the patient and doctor compared with other sources such as bone marrow. They are often used for tissue regeneration in combination with biomaterials. Adipose-derived stem cells can be applied unmodified or as single cell suspensions. However, certain pretreatments, such as cultivation under hypoxic conditions or three-dimensional spheroids production, may provide substantial benefit with regard to subsequent vascularization in vivo due to induced growth factor production. In this narrative review, derivatives of adipose tissue and the vascularization of biomaterials are addressed in a comprehensive approach, including several sizes of derivatives, such as whole fat flaps for soft tissue engineering, nanofat or stem cells, their secretome and exosomes. Taken together, it can be concluded that adipose tissue and its fractions down to the molecular level promote, enhance and support vascularization of biomaterials. Therefore, there is a high potential of the individual fat component to be used in regenerative medicine.

Evaluation of botulinum toxin A injections for the treatment of refractory chronic digital ulcers in patients with systemic sclerosis.

OBJECTIVES: To evaluate the therapeutic benefit of botulinum toxin A (BTX-A) injections for digital ulcers (DU) in patients with systemic sclerosis (SSc). METHODS: A systematic literature review was performed and the identified articles were selected by two reviewers and analysed with respect to date of publication, inclusion and exclusion criteria, number and age of participants, volume of BTX-A, injection sites, outcomes, and adverse events. In addition, in the Zurich cohort, 7 SSc patients were eligible for the study and were assessed for the duration of DU to heal, duration of DU-free periods, changes in frequency and numbers of prescribed vasodilators, pain and blood flow. RESULTS: In five articles from the systematic review, at least 48% of DU had healed and up to 100% reduction in VAS for pain was reported. Our 7 patients (median age of 53 (47-82) years) had in median 2.5 (2-4) DU and were injected with a median BTX-A volume of 90 (50-100) units per hand. Of the 31 DU in all patients, 77% (n=24) healed. Time to wound closure was in median 8 (4-12) weeks and the DU-free duration was in median 8 (3-10) months. In 80% of the cases, at least one vasodilator was stopped or could be administered less frequently. An improvement of blood flow and pain was reported in 60% of the cases. CONCLUSIONS: BTX-A injections might be of benefit for the treatment of chronic, refractory DU in selected SSc patients, yet a sufficiently powered prospective study will be needed as ultimate proof.

Supporting Cell-Based Tendon Therapy: Effect of PDGF-BB and Ascorbic Acid on Rabbit Achilles Tenocytes in Vitro.

Cell-based tendon therapies with tenocytes as a cell source need effective tenocyte in vitro expansion before application for tendinopathies and tendon injuries. Supplementation of tenocyte culture with biomolecules that can boost proliferation and matrix synthesis is one viable option for supporting cell expansion. In this in vitro study, the impacts of ascorbic acid or PDGF-BB supplementation on rabbit Achilles tenocyte culture were studied. Namely, cell proliferation, changes in gene expression of several ECM and tendon markers (collagen I, collagen III, fibronectin, aggrecan, biglycan, decorin, ki67, tenascin-C, tenomodulin, Mohawk, α-SMA, MMP-2, MMP-9, TIMP1, and TIMP2) and ECM deposition (collagen I and fibronectin) were assessed. Ascorbic acid and PDGF-BB enhanced tenocyte proliferation, while ascorbic acid significantly accelerated the deposition of collagen I. Both biomolecules led to different changes in the gene expression profile of the cultured tenocytes, where upregulation of collagen I, Mohawk, decorin, MMP-2, and TIMP-2 was observed with ascorbic acid, while these markers were downregulated by PDGF-BB supplementation. Vice versa, there was an upregulation of fibronectin, biglycan and tenascin-C by PDGF-BB supplementation, while ascorbic acid led to a downregulation of these markers. However, both biomolecules are promising candidates for improving and accelerating the in vitro expansion of tenocytes, which is vital for various tendon tissue engineering approaches or cell-based tendon therapy.

Directing Stem Cell Commitment by Amorphous Calcium Phosphate Nanoparticles Incorporated in PLGA: Relevance of the Free Calcium Ion Concentration.

The microenvironment of mesenchymal stem cells (MSCs) is responsible for the modulation in MSC commitment. Nanocomposites with an inorganic and an organic component have been investigated, and osteogenesis of MSCs has been attributed to inorganic phases such as calcium phosphate under several conditions. Here, electrospun meshes and two-dimensional films of poly(lactic-co-glycolic acid) (PLGA) or nanocomposites of PLGA and amorphous calcium phosphate nanoparticles (PLGA/aCaP) seeded with human adipose-derived stem cells (ASCs) were analyzed for the expression of selected marker genes. In a two-week in vitro experiment, osteogenic commitment was not found to be favored on PLGA/aCaP compared to pure PLGA. Analysis of the medium revealed a significant reduction of the Ca2+ concentration when incubated with PLGA/aCaP, caused by chemical precipitation of hydroxyapatite (HAp) on aCaP seeds of PLGA/aCaP. Upon offering a constant Ca2+ concentration, however, the previously observed anti-osteogenic effect was reversed: alkaline phosphatase, an early osteogenic marker gene, was upregulated on PLGA/aCaP compared to pristine PLGA. Hence, in addition to the cell-material interaction, the material-medium interaction was also important for the stem cell commitment here, affecting the cell-medium interaction. Complex in vitro models should therefore consider all factors, as coupled impacts might emerge.

Corticoperiosteal medial femoral condyle flap for recalcitrant nonunion in ankle and foot: Outcomes and radiological evaluation of donor site morbidity.

BACKGROUND: The aim of this study was to evaluate the effectiveness and safety of free corticoperiosteal medial femoral condyle (MFC) flap for ankle, hindfoot and midfoot reconstruction in patients with recalcitrant nonunion. METHODS: Patients who underwent ankle and foot reconstruction using the MFC flap at our clinic were recruited for assessment of the union rate, time to union and functional outcome. Furthermore, a clinical and radiological examination of the donor knee was performed using both computed tomography and magnetic resonance imaging. RESULTS: Thirteen patients with a mean follow-up time of 2.5 years were included; 10 of them had a previously failed ankle and foot arthrodesis. Union was achieved in 11 patients in an average time of 10 months after MFC flap surgery. Donor site morbidity was minor with no radiological evidence for soft tissue or bone complication. CONCLUSION: MFC flaps are a useful and safe reconstructive tool and may be considered after failed ankle and foot arthrodesis.

Cellular self-assembly into 3D microtissues enhances the angiogenic activity and functional neovascularization capacity of human cardiopoietic stem cells.

While cell therapy has been proposed as next-generation therapy to treat the diseased heart, current strategies display only limited clinical efficacy. Besides the ongoing quest for the ideal cell type, in particular the very low retention rate of single-cell (SC) suspensions after delivery remains a major problem. To improve cellular retention, cellular self-assembly into 3D microtissues (MTs) prior to transplantation has emerged as an encouraging alternative. Importantly, 3D-MTs have also been reported to enhance the angiogenic activity and neovascularization potential of stem cells. Therefore, here using the chorioallantoic membrane (CAM) assay we comprehensively evaluate the impact of cell format (SCs versus 3D-MTs) on the angiogenic potential of human cardiopoietic stem cells, a promising second-generation cell type for cardiac repair. Biodegradable collagen scaffolds were seeded with human cardiopoietic stem cells, either as SCs or as 3D-MTs generated by using a modified hanging drop method. Thereafter, seeded scaffolds were placed on the CAM of living chicken embryos and analyzed for their perfusion capacity in vivo using magnetic resonance imaging assessment which was then linked to a longitudinal histomorphometric ex vivo analysis comprising blood vessel density and characteristics such as shape and size. Cellular self-assembly into 3D-MTs led to a significant increase of vessel density mainly driven by a higher number of neo-capillary formation. In contrast, SC-seeded scaffolds displayed a higher frequency of larger neo-vessels resulting in an overall 1.76-fold higher total vessel area (TVA). Importantly, despite that larger TVA in SC-seeded group, the mean perfusion capacity (MPC) was comparable between groups, therefore suggesting functional superiority together with an enhanced perfusion efficacy of the neo-vessels in 3D-MT-seeded scaffolds. This was further underlined by a 1.64-fold higher perfusion ratio when relating MPC to TVA. Our study shows that cellular self-assembly of human cardiopoietic stem cells into 3D-MTs substantially enhances their overall angiogenic potential and their functional neovascularization capacity. Hence, the concept of 3D-MTs may be considered to increase the therapeutic efficacy of future cell therapy concepts.

Comparison of a New Inertial Sensor Based System with an Optoelectronic Motion Capture System for Motion Analysis of Healthy Human Wrist Joints.

This study aims to compare a new inertial measurement unit based system with the highly accurate but complex laboratory gold standard, an optoelectronic motion capture system. Inertial measurement units are sensors based on accelerometers, gyroscopes, and/or magnetometers. Ten healthy subjects were recorded while performing flexion-extension and radial-ulnar deviation movements of their right wrist using inertial sensors and skin markers. Maximum range of motion during these trials and mean absolute difference between the systems were calculated. A difference of 10° ± 5° for flexion-extension and 2° ± 1° for radial-ulnar deviation was found between the two systems with absolute range of motion values of 126° and 50° in the respective axes. A Wilcoxon rank sum test resulted in a no statistical differences between the systems with p-values of 0.24 and 0.62. The observed results are even more precise than reports from previous studies, where differences between 14° and 27° for flexion-extension and differences between 6° and 17° for radial-ulnar deviation were found. Effortless and fast applicability, good precision, and low inter-observer variability make inertial measurement unit based systems applicable to clinical settings.

Factors predicting the 1-year outcome of collagenase treatment for Dupuytren's disease.

INTRODUCTION: Several studies have investigated the clinical outcome after collagenase treatment for Dupuytren's disease in terms of range of motion of the affected finger. However, good objective clinical outcome defined by a small remaining flexion contracture does not necessarily translate into satisfactory patient-subjective hand function. The aim of the present study was to identify predictors of patient-reported as well as objective clinical outcome in patients 1 year after collagenase treatment for Dupuytren's disease. MATERIALS AND METHODS: Socio-demographic and disease-related data of 92 Dupuytren patients were collected prior to the intervention. Flexion contracture of the most affected finger was measured at baseline and 1 year after treatment. Patients also completed the brief Michigan Hand Outcomes Questionnaire (brief MHQ) before the intervention and at 1-year follow-up. First, univariate correlations using Pearson's correlation coefficient of the baseline variables with the two target variables were investigated. All variables with r > 0.35 were selected for a multivariate linear stepwise backwards regression model. RESULTS: The mean brief MHQ score increased between baseline (72 ± 14) and the 1-year follow-up (85 ± 15) (p ≤ 0.001) and baseline flexion contracture decreased from 76° (± 26) to 33° (± 31) (p ≤ 0.001). Higher hand function at baseline (R2 = 0.31) and less flexion contracture (R2 = 0.46) were identified as positive predictors for the outcome 1 year after collagenase treatment for Dupuytren's disease. Other variables such as age, gender, manual work and if the MCP or PIP joint was affected did not determine outcome in our patient series. CONCLUSIONS: Collagenase treatment resulted in considerable improvement in flexion contracture as well as patient-reported hand function at the 1-year follow-up. Clinicians can expect better outcome after collagenase infiltration in patients with less flexion contracture and in patients showing good initial self-reported hand function.

The Crucial Role of Vascularization and Lymphangiogenesis in Skin Reconstruction.

BACKGROUND: The treatment of extensive skin defects and bradytrophic wounds remains a challenge in clinical practice. Despite emerging tissue engineering approaches, skin grafts and dermal substitutes are still the routine procedure for the majority of skin defects. Here, we review the role of vascularization and lymphangiogenesis for skin grafting and dermal substitutes from the clinician's perspective. SUMMARY: Graft revascularization is a dynamic combination of inosculation, angiogenesis, and vasculogenesis. The majority of a graft's microvasculature regresses and is replaced by ingrowing microvessels from the wound bed, finally resulting in a chimeric microvascular network. After inosculation within 48-72 h, the graft is re-oxygenated. In contrast to skin grafts, the vascularization of dermal substitutes is slow and dependent on the ingrowth of vessel-forming angiogenic cells. Preclinical angiogenic strategies with adipose tissue-derived isolates are appealing for the treatment of difficult wounds and may markedly accelerate skin reconstruction in the future. However, their translation from bench to bedside is still restricted by major regulatory restrictions. Finally, the lymphatic system contributes to edema reduction and the removal of local wound debris. Therapeutic lymphangiogenesis is an emerging field of research in skin reconstruction. Key Messages: For the successful engraftment of skin grafts and dermal substitutes, the rapid formation of a microvascular network is of pivotal importance. Hence, to understand the biological processes behind revascularization of skin substitutes and to implement this knowledge into clinical practice is a prerequisite when treating skin defects. Furthermore, a functional lymphatic drainage crucially contributes to the engraftment of skin substitutes.

The novel treatment of SVF-enriched fat grafting for painful end-neuromas of superficial radial nerve.

INTRODUCTION: None of the existing treatments in the management of painful end-neuromas of the superficial branch of the radial nerve (SBRN) has been proven superior due to high levels of pain relapse. Fat grafts enriched with the stromal vascular fraction (SVF) could act as a mechanic barrier with biological effects decreasing the resorption rate and boosting the graft's regenerative potential. This study describes the novel surgical treatment technique of SVF-enriched fat grafting. PATIENTS AND METHODS: In this clinical study, five consecutive patients treated for painful end-neuromas of the SBRN between 2012 and 2013 were analyzed retrospectively. Microsurgical resection of end-neuromas followed by SVF-enriched fat grafting around the nerve stump was performed in all patients. Five different pain modalities and various predictors were compared pre- and up to 36 months postoperatively. RESULTS: Pain reduction observed at 2 months after surgery was constant over time, though not statistically significant compared to preoperative levels. Spontaneous pain could be reduced from 1.6 ± 0.55 to 1.2 ± 1.1 (p = 0.414), spikes from 2.2 ± 1.3 to 1.4 ± 1.34 (p = 0.180), hyperaesthesia from 1.6 ± 1.14 to 1.2 ± 1.64 (p = 0.713), tap pain from 2.8 ± 0.45 to 1.8 ± 1.3 (p = 0.197) and motion pain from 2.8 ± 0.45 to 1.4 ± 1.34 (p = 0.066). An improvement in overall pain reduction could be observed from 2.2 ± 0.97 to 1.4 ± 1.26 3 years after the surgery (p = 0.104). CONCLUSION: SVF-enriched fat grafting represents another alternative to numerous available treatments of painful end-neuromas of the SBRN. Our preliminary results could not show any significant difference in pain reduction following SVF-enriched fat grafting. Further larger trials are required in order to evaluate the therapeutic potential of SVF-enriched fat grafting.