Intradermal and transdermal absorption of beta-naphthylamine and N-Phenyl-beta-naphthylamine in a viable human skin model.

Technical products containing N-Phenyl-beta-naphthylamine (PBNA) are contaminated with beta-naphthylamine (BNA), a known carcinogen. Both amines penetrate the skin to different degrees, but little is known about their dermal-depot formation. This study investigated the dermal penetration of PBNA and its degradation product BNA using a viable human-skin model. PBNA (259 µg) or BNA (0.52 µg) in n-hexane and industrial grease were applied to freshly excised human skin (n = 6, 0.64 cm2) for 2-72 h. After temporary/continuous and single/repeated exposure, samples were taken (stratum corneum, epidermis/dermis, receptor fluid) and analyzed for their amine content by GC-MS. Continuous exposure led to a PBNA dermal depot of ∼47 µg/cm2 over 72 h. Temporary applications also resulted in lower but consistent PBNA dermal depots. A single 2-h application resulted in a dermal depot of ∼16 µg/cm2 after 72 h, while this was ∼25 µg/0.64 cm2 with repeated applications. BNA behaved differently; with repeated 2-h applications, intradermally retained BNA initially increased 3-6 fold, then dropped to ∼200-250 ng/cm2. This incomplete decline upon repeated short-term exposure to PBNA suggests that a BNA dermal depot is formed either due to contamination of PBNA with BNA or to enzymatic conversion of PBNA to BNA. Additionally, PBNA dermal depots were saturable under the given conditions. These findings highlight the importance of understanding the dermal-exposure dynamics of potential carcinogenic compounds in industrial settings.

The Effect of Ionizing Irradiation on the Autotaxin-Lysophasphatidic Acid Axis and Interleukin-6/8 Secretion in Different Breast Cancer Cell Lines.

BACKGROUND: The Autotaxin (ATX)-lysophosphatidic acid (LPA) axis is involved in decreasing radiation sensitivity of breast tumor cells. This study aims to further elucidate the effect of irradiation on the ATX-LPA axis and cytokine secretion in different breast cancer cell lines to identify suitable breast cancer subtypes for targeted therapies. METHODS: Different breast cancer cell lines (MCF-7 (luminal A), BT-474 (luminal B), SKBR-3 (HER2-positive), MDA-MB-231 and MDA-MB-468 (triple-negative)) and the breast epithelial cell line MCF-10A were irradiated. The influence of irradiation on LPA receptor (LPAR) expression, ATX expression, and Interleukin (IL)-6 and IL-8 secretion was analyzed. Further, the effect of IL-6 and IL-8 on ATX expression of adipose-derived stem cells (ADSC) was investigated. RESULTS: Irradiation increased ATX and LPAR2 expression in MDA-MB-231 cells. Additionally, IL-6 secretion was enhanced in MDA-MB-231, and IL-8 secretion in MDA-MB-231 and MDA-MB-468. Stimulation of ADSC with IL-6 and IL-8 increased ATX expression in ADSC. CONCLUSIONS: Targeting ATX or its downstream signaling pathways might enhance the sensitivity of triple-negative breast cancer cells to radiation. Further exploration of the interplay between irradiation, the ATX-LPA axis, and inflammatory cytokines may elucidate novel pathways for overcoming radioresistance and improving individual treatment outcomes.

[Reconstruction of Oncological Defects in the Pelvic-perineal Region: Report on the Consensus Workshop at the 44th Annual Meeting of the DAM 2023 in Bern, CH]. / Rekonstruktion onkologischer Defekte im Becken-Perinealbereich ­ Bericht zum Konsensus-Workshop im Rahmen der 44. Jahrestagung der DAM 2023 in Bern, CH.

The surgical-oncological treatment of pelvic and perineal malignancies is associated with a high complication rate and morbidity for patients. Modern multimodal treatment modalities, such as neoadjuvant radio-chemotherapy for anal or rectal cancer, increase the long-term survival rate while reducing the risk of local recurrence. Simultaneously, the increasing surgical radicality and higher oncological safety with wide resection margins is inevitably associated with larger and, due to radiation, more complex tissue defects in the perineal and sacral parts of the pelvic floor. Therefore, the plastic-surgical reconstruction of complex pelvic-perineal defects following oncological resection remains challenging. The reconstructive armamentarium, and thus the treatment of such defects, is broad and ranges from local, regional and muscle-based flaps to microvascular and perforator-based procedures. While the use of flaps is associated with a significant, well-documented reduction in postoperative complications compared to primary closure, there is still a lack of reliable data directly comparing the postoperative results of different reconstructive approaches. Additionaly, the current data shows that the quality of life of these patients is rarely recorded in a standardised manner. In a consensus workshop at the 44th annual meeting of the German-speaking Association for Microsurgery on the topic of "Reconstruction of oncological defects in the pelvic-perineal area", the current literature was discussed and recommendations for the reconstruction of complex defects in this area were developed. The aim of this workshop was to identify knowledge gaps and establish an expert consensus to ensure and continuously improve the quality of reconstruction in this challenging area. In addition, the importance of the "patient-reported outcome measures" in pelvic reconstruction was highlighted, and the commitment to its widespread use in the era of value-based healthcare was affirmed.

Mapping wrist motion: 3D CT analysis after scapholunate ligament transection.

The injury of the scapholunate (SL) ligament is common in wrist traumas leading to pain and reduced wrist function. The wrist's unique joint design and possible underlying theories as the carpal row theory were subject to earlier investigations studying wrist kinematics. Nevertheless, a comprehensive understanding of how SL ligament injuries affect wrist biomechanics is still lacking. Through a quantitative analysis of carpal bone motion patterns, we evaluated the impact on wrist kinematics occurring after SL ligament injury. We conducted a study using computer tomography imaging to analyse wrist kinematics after SL ligament transection in 21 fresh-frozen anatomical specimens. The collected data were then transformed into 3D models, employing both standardized global and object coordinate systems. The study encompassed the evaluation of rotation and translation for each individual carpal bone, as well as the ulna, and all metacarpal bones in reference to the radius. The study showed a significant increase in rotation towards palmar (p < 0.01), particularly notable for the scaphoid, following transection of the SL ligament during palmar flexion. Ulnar deviation did not significantly affect rotation or translation, and radial deviation also showed no significant changes in rotation or translation. The study highlights the significance of the SL ligament in wrist kinematics, revealing that SL ligament tears lead to changes in wrist motion. While we observed significant rotational changes for the scaphoid, other carpal bones showed less pronounced alterations, emphasizing the complexity of wrist biomechanics.

Introducing a Simple Tool of Patient Self-Assessment of Wrist Range of Motion.

Hand disorders can reduce wrist range of motion (ROM). The SARS-CoV-2 pandemic highlighted challenges in routine follow-up exams, making telemedicine a viable solution. This study evaluates the feasibility and accuracy of patient self-measured wrist ROM using a self-designed goniometer template. The template was designed to measure flexion/extension and radial/ulnar abduction movements. A cohort of 50 adults (25 males/25 females) participated in this prospective study. The exclusion criteria included wrist immobilization and ages outside of 18-65 years. Participants self-assessed their wrist ROM with the goniometer template. Measurements were independently performed by a student and a specialist using standard goniometry, as well as a resident using the self-designed goniometer. The results were blinded for unbiased analysis. Mean differences in ROM varied across movement directions, with minimal differences for ulnar abduction and more substantial deviations for radial abduction, extension and flexion. The patient-specialist comparison showed deviations below 5 degrees for flexion and ulnar abduction in 50% of cases. Telemedicine, expanded by the COVID-19 pandemic, offers significant potential for hand rehabilitation. Current methods of ROM assessment lack cost-effectiveness and simplicity. Our method, demonstrating comparable accuracy for most movements, provides a cost-effective, reliable alternative for remote ROM assessment, enhancing telemedicine practices in hand rehabilitation.

[Long-Term Outcome of Digital Defect Reconstruction using Cross-Finger Flaps]. / Langzeitergebnisse nach Rekonstruktion von Fingerdefekten mittels Cross-Finger-Lappenplastik.

INTRODUCTION: Although multiple advances have been made in finger defect reconstruction, cross-finger flaps remain an important reconstructive tool. However, data on long-term results are scarce in the literature. This study aimed to assess the clinical and subjective long-term outcomes of patients who underwent cross-finger flap reconstruction for palmar digital and fingertip defects. PATIENTS AND METHODS: Between January 2003 and July 2022, 35 patients (31 male, 4 female, mean age: 59.0 years±20.1) were screened and included in the study. The data were obtained through a clinical examination, a Quick-DASH score and a self-designed questionnaire. Clinical outcomes were assessed by evaluating the range of motion (ROM) of the reconstructed finger and the donor finger compared with the contralateral uninjured hand. In addition to ROM, a static two-point separation test was performed to assess the sensory function of the reconstructed finger. The follow-up period was between 1 year and 19 years (mean: 12.6 years±6.1). RESULTS: There was no significant difference in terms of ROM between the reconstructed finger and the donor finger compared with the contralateral uninjured hand. All patients reported normal discrimination between sharp and blunt objects. However, there was a significant difference in two-point discrimination between the reconstructed finger and the healthy contralateral finger (p<0.05). The average Quick-DASH score was 5.1 points. Satisfaction with the functional outcome in terms of mobility and load-bearing capacity of the cross-finger flap averaged 8.1 out of 10 points. Satisfaction with the aesthetic outcome of the reconstructed finger averaged 7.7 out of 10 points. In 4 cases, persistent pain was reported when the reconstructed finger was under stress. No cases of pain at rest were reported. CONCLUSION: In the long run, cross-finger flaps are a safe and effective reconstructive procedure for covering defects in palmar injuries of the finger and fingertip amputation. They represent a simple, reliable, long-lasting reconstructive technique. The necessary temporary iatrogenic syndactyly does not lead to long-term limitations in the range of motion.

Application of Near Infrared Spectroscopy to Enhance Safety and Individualize Distraction of Severely Contracted Joints in Far-Advanced Dupuytren's Disease.

Background: Slow distraction of contracted joints is a well-established treatment in far-advanced stages of Dupuytren's disease (DD). To assess finger perfusion and avoid malperfusion, we studied near infrared spectroscopy (NIRS) to evaluate the maximum extent of distraction that would not harm microcirculation to the finger. This technique also allows an optimized treatment in accordance with sufficient blood perfusion during distraction. Methods: Eligible patients with stage IV finger contractures who needed treatment for Dupuytren's contracture were included and prospectively investigated. The operation was performed with local anaesthesia. First, the Dupuytren strand of the treated finger was dissected in the palm to allow distraction. Under X-ray control, the distraction device was applied. Then, slow distraction of the treated joint was performed to evaluate the finger perfusion. To assess perfusion of the treated finger, NIRS was used to measure tissue oxygen saturation. If impaired finger perfusion was detected, traction was reduced until sufficient oxygen levels and perfusion patterns were reestablished. Results: NIRS was performed after application of the distraction device in seven cases. We treated six male and one female patient (mean age 70 years, range 51-80 years). Rapid distraction resulted in malperfusion of the treated fingers. Using NIRS proved to render reliable and reproducible information on finger perfusion and oxygenation in all seven patients. Conclusions: Application of NIRS enhances safety in the treatment of far-advanced DD finger contractures with an external skeletal distraction device. It is non-invasive, reproducible, easy to use and allows for an individualized adapted distraction velocity.

Vein Visualization With a Near Infrared Imaging Device and Its Impact on Students' and Nurses' Skills in an Academic Teaching University Hospital.

Venipuncture for blood collection is frequently delegated to medical or nursing students, while their individual skills depend on the quality of teaching. The aim of this study was to evaluate the use of a near infrared imaging (NIR) system on the visualization of veins and its potential benefit for the education of medical personnel. Participants answered a questionnaire following standardized venipuncture for blood sampling with the help of an NIR device. Vein visibility with the NIR device and its ability to facilitate venipuncture were examined. Visibility of veins was significantly better with the NIR, and its direction was clearly delineated. Sixty-nine percent of the participants stated that they felt more secure with venipuncture after using the NIR device. Patients' individual factors limited the visibility of veins. The adjuvant use of an NIR system for venipuncture improves participants' subjective skills through visualization of veins and their direction.

Application of Stem Cells Shows Antiinflammatory Effect in an Irradiated Random Pattern Flap Model.

BACKGROUND: In reconstructive surgery, local flaps might develop tissue necrosis or partial flap loss especially after previous irradiation, which may be necessary in many tumor entities. The application of stem cells seems promising to improve flap perfusion and might be a possible solution to optimize flap survival. METHODS: Twenty rats received harvesting of bilateral random pattern fasciocutaneous flaps. The right flaps received 20 Gy ionizing radiation 4 weeks prior to the surgery, while the left flaps served as the non-irradiated control. After flap harvest, four different stem cell mixtures (5 × 106 ASC, ASC-HUVEC, MSC, MSC-HUVEC) were applied under both right and left flaps using 1 mL fibrin glue as the delivery vehicle. Flap size and its necrotic area were examined clinically. Two weeks after the surgery, HE staining and immunohistochemical staining for CD68 and ERG, as well as PCR analysis (Interleukin 6, HIF-1α and VEGF), were performed. RESULTS: Application of ASCs, ASCs-HUVECs and MSCs resulted in a lower number of CD68-stained cells compared to the no cell group. The expression of Hif1α was higher in the ASC group compared to those in the MSC and previously treated no cell groups. Treatment with MSCs and MSCs-HUVECs prevented shrinking of the flaps in this series. CONCLUSION: Application of ASCs, MSCs and ASCs-HUVECs was shown to have an antiinflammatory effect. Treatment with MSCs and MSCs-HUVECs can prevent early shrinking of the flaps.

Analysis of laboratory markers in body contouring procedures after bariatric surgery does not indicate particular risks for perioperative complications.

BACKGROUND: Body contouring surgery after massive weight loss is associated with different risk factors. Wound healing disorders and seromas commonly occur postoperatively. Bariatric interventions lead to massive weight loss with excess skin and soft tissue. In this study, perioperatively collected laboratory markers of this special patient population were analyzed. METHODS: Fifty-nine patients were analyzed retrospectively regarding bariatric surgery, weight loss, body contouring surgery, laboratory markers, and complication rates. RESULTS: Body contouring surgery (n = 117) was performed in 59 patients. Weight loss was achieved after gastric bypass (40.1%), gastric banding (33.9%), or sleeve gastrectomy (26.0%), with an average of 69.2 kg. The most common body contouring procedure included abdominoplasty (n = 50), followed by thigh lift (n = 29), mammaplasty (n = 19), brachioplasty (n = 14), and upper body lift (n = 5). Analysis of laboratory markers revealed no exceptional and clinically relevant variations. Correlation analysis revealed associations between resection weight, amount of drain fluid, and particular laboratory markers. CONCLUSION: Analysis of perioperative laboratory markers in this special patient population after massive weight loss did not indicate clinically relevant risk factors regardless of the type of bariatric or body contouring surgery. Body contouring surgeries after bariatric interventions prove to be safe and low risk concerning perioperative laboratory markers and postoperative hospitalization.

Characterization of two different alginate-based bioinks and the influence of melanoma growth within.

Extrusion-based bioprinting is an established method in biofabrication. Suitable bioinks have fundamentally different compositions and characteristics, which should be examined, in order to find a perfect model system. Here, we investigate the effect of two alginate-based, yet unalike 3D-printed bioinks, pre-crosslinked alginate-dialdehyde gelatin (ADA-GEL) and a mixture of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), on the melanoma cell line Mel Im and vice versa in terms of stiffness, shrinkage, cellular behavior and colony formation over 15 days. Rheological stiffness measurements revealed two soft gels with similar storage moduli. The cells did not have a significant impact on the overall stiffness, whereas ADA-GEL (2.5/2.5%) was significantly stiffer than Alg/HA/Gel (0.5/0.1/3%). Regarding the shrinkage of printed constructs, cells had a significant influence, especially in ADA-GEL, which has covalent bonds between the oxidized alginate and gelatin. Multi-photon microscopy exhibited proliferation, cell spreading and migration in ADA-GEL with cell-cell and cell-matrix interaction, dissimilarly to Alg/HA/Gel, in which cells formed spherical, encapsulated colonies. Scanning electron microscopy and histology showed degradation and multi-layered growth on ADA-GEL and fewer examples of escaped cells on Alg/HA/Gel. Both gels serve as proliferation bioink for melanoma with more necrosis in deeper Alg/HA/Gel colonies and differences in spreading and matrix interaction. These findings show the importance of proper characterization of the bioinks for different applications.

A vascularized in vivo melanoma model suitable for metastasis research of different tumor stages using fundamentally different bioinks.

Although 2D cancer models have been the standard for drug development, they don't resemble in vivo properties adequately. 3D models can potentially overcome this. Bioprinting is a promising technique for more refined models to investigate central processes in tumor development such as proliferation, dormancy or metastasis. We aimed to analyze bioinks, which could mimic these different tumor stages in a cast vascularized arteriovenous loop melanoma model in vivo. It has the advantage to be a closed system with a defined microenvironment, supplied only with one vessel-ideal for metastasis research. Tested bioinks showed significant differences in composition, printability, stiffness and microscopic pore structure, which led to different tumor stages (Matrigel and Alg/HA/Gel for progression, Cellink Bioink for dormancy) and resulted in different primary tumor growth (Matrigel significantly higher than Cellink Bioink). Light-sheet fluorescence microscopy revealed differences in vascularization and hemorrhages with no additional vessels found in Cellink Bioink. Histologically, typical human melanoma with different stages was demonstrated. HMB-45-positive tumors in progression inks were infiltrated by macrophages (CD163), highly proliferative (Ki67) and metastatic (MITF/BRN2, ATX, MMP3). Stainings of lymph nodes revealed metastases even without significant primary tumor growth in Cellink Bioink. This model can be used to study tumor pathology and metastasis of different tumor stages and therapies.

The Impact of Technical Innovations and Donor-Site Mesh Repair on Autologous Abdominal-Based Breast Reconstruction-A Retrospective Analysis.

Background: The aim of this study was to examine the potential benefit that may be achieved through the introduction of technical innovations and the incorporation of mesh for fascial donor site closure in uni- and bilateral autologous breast reconstruction with abdominal tissue. Methods: A retrospective single-center review of all breast reconstructions with a DIEP or MS-TRAM flap between January 2004 and December 2019 was performed. Donor and recipient site complications and operation times were evaluated before and after the implementation of coupler anastomoses, preoperative computed tomography angiography (CTA), indocyanine green (ICG) angiography, and the inclusion of mesh in donor site repair. Results: A total of 396 patients were included, accounting for 447 flaps. Operation time was significantly shorter in unilateral reconstructions after the implementation of CTA (p < 0.0001). ICG angiography significantly reduced the rates of partial flap loss (p = 0.02) and wound healing disorders (p = 0.02). For unilateral reconstructions, abdominal bulging or hernia was observed more often in MS1-TRAM flaps without synthetic mesh repair (p = 0.001), whereas conservatively treated seroma developed more frequently after mesh implantation (p = 0.03). Conclusions: Recent technological advancements developed over the past few decades have made a substantial impact on decreasing surgical duration and enhancing procedure safety.

[Postbariatric plastic surgery for body reconstruction]. / Postbariatrische plastische Körperrekonstruktionen.

Massive weight loss following bariatric surgery is often accompanied by functional impairments due to the resulting excess skin and soft tissues. To achieve both functional reconstruction and restoration of the body silhouette, it is imperative to undergo body contouring surgery involving the strategic transposition of tissues. Several surgical techniques are available for the affected body regions and their application for treatment is determined by the unique circumstances specific to each patient. When conducted by skilled practitioners, postbariatric body reconstruction can be executed safely, leading to outcomes that are both functionally and esthetically satisfying, ultimately contributing to an enhanced quality of life for patients. This article provides the fundamental principles for patient selection, surgical preparation, treatment planning, surgical techniques and the postoperative care following bariatric surgery.

Schwann Cells Do Not Promote Myogenic Differentiation in the EPI Loop Model.

In skeletal muscle tissue engineering, innervation and vascularization play an essential role in the establishment of functional skeletal muscle. For adequate three-dimensional assembly, biocompatible aligned nanofibers are beneficial as matrices for cell seeding. The aim of this study was to analyze the impact of Schwann cells (SC) on myoblast (Mb) and adipogenic mesenchymal stromal cell (ADSC) cocultures on poly-ɛ-caprolactone (PCL)-collagen I-nanofibers in vivo. Human Mb/ADSC cocultures, as well as Mb/ADSC/SC cocultures, were seeded onto PCL-collagen I-nanofiber scaffolds and implanted into the innervated arteriovenous loop model (EPI loop model) of immunodeficient rats for 4 weeks. Histological staining and gene expression were used to compare their capacity for vascularization, immunological response, myogenic differentiation, and innervation. After 4 weeks, both Mb/ADSC and Mb/ADSC/SC coculture systems showed similar amounts and distribution of vascularization, as well as immunological activity. Myogenic differentiation could be observed in both groups through histological staining (desmin, myosin heavy chain) and gene expression (MYOD, MYH3, ACTA1) without significant difference between groups. Expression of CHRNB and LAMB2 also implied neuromuscular junction formation. Our study suggests that the addition of SC did not significantly impact myogenesis and innervation in this model. The implanted motor nerve branch may have played a more significant role than the presence of SC.

Quick and safe: why a k-wire-extension-block-fixation of a bony mallet finger is the favoured treatment.

INTRODUCTION: Mallet fingers are the most common tendon injuries of the hand. Bony avulsion distal finger extensor tendon ruptures causing a mallet finger require special attention and management. In this monocentral study, we analyzed the clinical and individual outcomes succeeding minimal invasive k-wire extension block treatment of bony mallet fingers. MATERIALS AND METHODS: In a retrospective study, we sent a self-designed template and a QUICK-DASH score questionnaire to all patients, who were treated because of a bony mallet finger between 2009 and 2022 and fulfilled the inclusion criteria. A total of 244 requests were sent out. 72 (29.5%) patients participated in the study. Forty-five men and twenty-seven women were included. RESULTS: 98.7% (n = 75) of the cases were successfully treated. Patients were highly satisfied with the treatment (median 8.0; SD ± 2.9; range 1.0-10.0). Based on the QUICK-DASH score, all patients showed no difficulties in daily life. The extent of avulsion did not influence the outcome. CONCLUSION: We conclude that the minimally invasive treatment of a bony mallet finger should be offered to every patient, because it is safe, fast, and reliable. Thus, we propose to perform extension-block pinning independently of the articular area.

Variation in cartilage T2 and T2* mapping of the wrist: a comparison between 3- and 7-T MRI.

BACKGROUND: To analyze regional variations in T2 and T2* relaxation times in wrist joint cartilage and the triangular fibrocartilage complex (TFCC) at 3 and 7 T and to compare values between field strengths. METHODS: Twenty-five healthy controls and 25 patients with chronic wrist pain were examined at 3 and 7 T on the same day using T2- and T2*-weighted sequences. Six different regions of interest (ROIs) were evaluated for cartilage and 3 ROIs were evaluated at the TFCC based on manual segmentation. Paired t-tests were used to compare T2 and T2* values between field strengths and between different ROIs. Spearman's rank correlation was calculated to assess correlations between T2 and T2* time values at 3 and 7 T. RESULTS: T2 and T2* time values of the cartilage differed significantly between 3 and 7 T for all ROIs (p ≤ 0.045), with one exception: at the distal lunate, no significant differences in T2 values were observed between field strengths. T2* values differed significantly between 3 and 7 T for all ROIs of the TFCC (p ≤ 0.001). Spearman's rank correlation between 3 and 7 T ranged from 0.03 to 0.62 for T2 values and from 0.01 to 0.48 for T2* values. T2 and T2* values for cartilage varied across anatomic locations in healthy controls at both 3 and 7 T. CONCLUSION: Quantitative results of T2 and T2* mapping at the wrist differ between field strengths, with poor correlation between 3 and 7 T. Local variations in cartilage T2 and T2* values are observed in healthy individuals. RELEVANCE STATEMENT: T2 and T2* mapping are feasible for compositional imaging of the TFCC and the cartilage at the wrist at both 3 and 7 T, but the clinical interpretation remains challenging due to differences between field strengths and variations between anatomic locations. KEY POINTS: •Field strength and anatomic locations influence T2 and T2* values at the wrist. •T2 and T2* values have a poor correlation between 3 and 7 T. •Local reference values are needed for each anatomic location for reliable interpretation.

Intraoperative Blood Flow Analysis of Free Flaps with Arteriovenous Loops for Autologous Microsurgical Reconstruction.

BACKGROUND: Arteriovenous (AV) loops help to overcome absent or poor-quality recipient vessels in highly complex microvascular free flap reconstruction cases. There are no studies on blood flow and perfusion patterns. The purpose of this study was to evaluate and compare intraoperative hemodynamic characteristics of AV loops followed by free tissue transfer for thoracic wall and lower extremity reconstruction. METHODS: this prospective clinical study combined Transit-Time Flowmetry and microvascular Indocyanine Green Angiography for the assessment of blood flow volume, arterial vascular resistance and intrinsic transit time at the time of AV loop construction and on the day of free flap transfer. RESULTS: A total of 11 patients underwent AV loop creation, of whom five required chest wall reconstruction and six required reconstruction of the lower extremities. In seven of these cases, the latissimus dorsi flap and in four cases the vertical rectus abdominis myocutaneous (VRAM) flap was used as a free flap. At the time of loop construction, the blood flow volume of AV loops was 466 ± 180 mL/min, which increased to 698 ± 464 mL/min on the day of free tissue transfer (p > 0.1). After free flap anastomosis, the blood flow volume significantly decreased to 18.5 ± 8.3 mL/min (p < 0.001). There was no significant difference in blood flow volume or arterial vascular resistance between latissimus dorsi and VRAM flaps, nor between thoracic wall and lower extremity reconstruction. However, a significant correlation between the flap weight and the blood flow volume, as well as to the arterial vascular resistance, was found (p < 0.05). CONCLUSION: This is the first study to perform intraoperative blood flow and hemodynamic measurements of AV loops followed by free tissue transfer. Our results show hemodynamic differences and contribute to deeper understanding of the properties of AV loops for free flap reconstruction.

Perspectives on the Current State of Bioprinted Skin Substitutes for Wound Healing.

Human skin is particularly vulnerable to external damaging influences such as irradiation, extreme temperatures, chemical trauma, and certain systemic diseases, which reduce the skin's capacity for regeneration and restoration and can possibly lead to large-scale skin defects. To restore skin continuity in severe cases, surgical interventions such as the transplantation of autologous tissue are needed. Nevertheless, the coverage of larger skin defects caused by severe third-grade burns or extensive irradiation therapy is limited due to the depletion of uninjured autologous tissue. In such cases, many of the patient's epidermal cells can become available using biofabricated skin grafts, thereby restoring the skin's vital functions. Given the limited availability of autologous skin grafts for restoring integrity in large-scale defects, using bioprinted constructs as skin graft substitutes could offer an encouraging therapeutic alternative to conventional therapies for large-scale wounds, such as the transplantation of autologous tissue. Using layer-by-layer aggregation or volumetric bioprinting, inkjet bioprinting, laser-assisted bioprinting, or extrusion-based bioprinting, skin cells are deposited in a desired pattern. The resulting constructs may be used as skin graft substitutes to accelerate wound healing and reconstitute the physiological functions of the skin. In this review, we aimed to elucidate the current state of bioprinting within the context of skin tissue engineering and introduce and discuss different bioprinting techniques, possible approaches and materials, commonly used cell types, and strategies for graft vascularization for the production of bioprinted constructs for use as skin graft substitutes.