Full-thickness Tissue Research Articles

Assessing nanotoxicity of food-relevant particles: A comparative analysis of cellular responses in cell monolayers versus 3D gut epithelial cultures

Engineered nanoparticles (NPs) are extensively used in the food industry, yet safety concerns remain. The lack of validated methodologies is a bottleneck towards resolving this uncertainty. Hence, the current study aims to compare two cell models by examining the toxicological impacts of two food-relevant NPs (SiO2 and Ag) on intestinal epithelia using monolayer Caco-2 cells and full-thickness 3D tissue models of human small intestines (EpiIntestinal™). Comprehensive characterization and dosimetric analysis of the NPs were performed to determine effective doses and model realistic exposures. Neither genotoxicity nor cytotoxicity were detected in the 3D tissues after NP treatment, while the 2D cultures exhibited cytotoxic response from Ag NP treatment for 24 h at 1 μg/ml. Hyperspectral imaging and transmission electron microscopy confirmed uptake of both NPs by cells in both 2D and 3D culture models. Ag NPs caused an increase in autophagy, whereas SiO2 NPs induced increased cytoplasmic vacuolization. Based on realistic exposure levels studied, the 3D small intestinal tissue model was found to be more resilient to NP treatment compared to 2D cell monolayers. This comparative approach towards toxicological assessment of food relevant NPs could be used as a framework for future analysis of NP behavior and nanotoxicity in the gut.

Repair of mitral paravalvular leak using left atrial appendage tissue.

Paravalvular leak after mitral valve replacement causes serious symptoms such as heart failure and haemolysis. However, whether re-replacement or direct leak site repair is the appropriate surgical treatment for this condition remains controversial. Herein, we describe a case of paravalvular leak repaired using left atrial appendage tissue with excellent results. The proposed technique enables the repair of a leak at the 9 o'clock position with healthy, full-thickness autologous tissue. For this method, the leak must be located near the left atrial appendage, and the left atrial appendage must not adhere to the pericardial sac. Although this technique can only be used under specific conditions, it is a useful option for cardiac surgeons.

Structural and molecular characteristics of weight-bearing volar skin can be reconstituted by micro skin tissue column grafting.

For patients with lower limb amputations, prostheses are immensely helpful for mobility and the ability to perform job-related or recreational activities. However, the skin covering the amputation stump is typically transposed from adjacent areas of the leg and lacks the weight-bearing capacity that is only found in the specialized skin covering the palms and soles (a.k.a. volar skin). As a result, the skin tissue in direct contact with the prosthesis frequently breaks down, leading to the development of painful sores and other complications that limit, and often preclude, the use of prostheses. Transplanting volar skin onto amputation stumps could be a solution to these problems, but traditional skin transplantation techniques cause substantial morbidity at the donor site, such as pain and scarring, which are especially problematic for volar skin given the critical functional importance of the volar skin areas. We previously developed the technology to collect and engraft full-thickness skin tissue while avoiding long-term donor site morbidity, by harvesting the skin in the form of small (~0.5 mm diameter) cores that we termed "micro skin tissue columns" (MSTCs), so that each donor wound is small enough to heal quickly and without clinically appreciable scarring or other long-term abnormalities. The goal of this study was to establish whether a similar approach could be used to confer the structural and molecular characteristics of volar skin ectopically to other skin areas. In a human-to-mouse xenograft model, we show the long-term persistence of various human plantar MSTC-derived cell types in the murine recipient. Then in an autologous porcine model, we harvested MSTCs from the bottom of the foot and transplanted them onto excision wounds on the animals' trunks. The healing processes at both the donor and graft sites were monitored over 8 weeks, and tissue samples were taken to verify volar-specific characteristics by histology and immunohistochemistry. The volar donor sites were well-tolerated, healed rapidly, and showed no signs of scarring or any other long-term defects. The graft sites were able to maintain volar-specific histologic features and expression of characteristics protein markers, up to the 8-week duration of this study. These results suggest that MSTC grafting could be a practical approach to obtain autologous donor volar skin tissue, confer volar skin characteristics ectopically to nonvolar skin areas, improve the load-bearing capacity of amputation stump skin, and ultimately enhance mobility and quality-of-life for lower limb amputees.

Reduced endometrial glycolysis concomitant with increased lesional fibrosis in patients with adenomyosis who complained of heavy menstrual bleeding

RESEARCH QUESTIONWhat role, if any, does the extent of lesional fibrosis play in adenomyosis-associated heavy menstrual bleeding (ADM-HMB)? DESIGNForty-eight patients with ADM-HMB were recruited, among them 25 reported moderate/heavy bleeding (MHB) and the remaining 23, excessive bleeding (EXB). The full-thickness uterine tissue columns were processed for Masson trichrome staining and immunohistochemistry analyses. The levels of HIF-1α, GLUT1, HK2, PFKFB3 and PKM2—proteins critically involved in glycolysis—in endometrial epithelial cells cultured on substrates of different stiffness, and the levels of glycolysis were quantitated. A mouse experiment with induced adenomyosis and simulated menstrual bleeding was conducted to assess the impact of adenomyosis on immunoexpression of proteins involved in glycolysis and inflammation as well as on endometrial repair and bleeding. RESULTSThe endometrial staining of HIF-1α, GLUT1, HK2, PFKFB3 and PKM2 was significantly lower in the EXB group as compared with MHB patients, concomitant with higher extent of fibrosis. The expression of HIF-1α, GLUT1, HK2, PFKFB3 and PKM2 was significantly reduced when endometrial epithelial cells were cultured in stiff substrate, concomitant with reduced glycolysis. Mice with induced adenomyosis exhibited reduced immunoexpression of Hif-1α, as well as those proteins each of which plays a vital, rate-limiting role in different steps of the glycolysis pathway, such as Glut1, Hk2, Pfkfb3 and Pkm2, and elevated fibrosis in endometrium, concomitant with disrupted endometrial repair and more bleeding. CONCLUSIONSLesional fibrosis results in reduced endometrial glycolysis in eutopic endometrium and subsequent imbalance in pro- and anti-inflammatory response, leading to ADM-HMB.

Key extracellular proteins and TF-miRNA co-regulatory network in diabetic foot ulcer: Bioinformatics and experimental insights.

Diabetic foot ulcers (DFUs), a serious complication of diabetes, are associated with abnormal extracellular protein (EP) metabolism. The identification of key EPs and their regulatory networks is crucial for the understanding of DFU formation and development of effective treatments. In this study, a large-scale bioinformatics analysis was conducted to identify potential therapeutic targets and experimental validation was performed to ensure the reliability and biological relevance of the findings. Due to the comprehensive profiling of DFU samples provided by the GSE80178 dataset, we initially selected it to derive differentially expressed genes (DEGs) associated with DFU. Subsequently, utilizing the UniProt database and annotated EP list from the Human Protein Atlas annotation database, we screened for extracellular protein-related differentially expressed genes (EP-DEGs) due to their crucial role in the pathogenesis and healing of DFU. We examined EP-DEG pathway enrichment and protein-protein interaction networks, analyzed paired full-thickness skin tissue samples from 24 patients with DFUs and healthy controls, and performed polymerase chain reaction (PCR) experiments to validate candidate genes. Ultimately, we constructed a transcription factor (TF)-microRNA (miRNA)-hub gene co-regulatory network to explore upstream and downstream regulatory connections based on validated DEGs. Four crucial candidate genes (FMOD, LUM, VCAN, and S100A12) were identified and verified via PCR analysis. The TF-miRNA-hub EP-DEG regulatory network contained the pivotal TFs TRIM28 and STAT3 and the miRNAs hsa-mir-20a-5p, hsa-miR-21, and hsa-miR-203. The findings of this study advance our understanding of the pathology of DFU by defining key roles of specific EPs and elucidating a comprehensive regulatory network. These insights pave the way for novel approaches to improve DFU treatment outcomes.

The human colon: Evidence for degenerative changes during aging and the physiological consequences.

The incidence of constipation increases among the elderly (>65 years), while abdominal pain decreases. Causes include changes in lifestyle (e.g., diet and reduced exercise), disease and medications affecting gastrointestinal functions. Degenerative changes may also occur within the colo-rectum. However, most evidence is from rodents, animals with relatively high rates of metabolism and accelerated aging, with considerable variation in time course. In humans, cellular and non-cellular changes in the aging intestine are poorly investigated. To examine all available studies which reported the effects of aging on cellular and tissue functions of human isolated colon, noting the region studied, sex and age of tissue donors and study size. The focus on human colon reflects the ability to access full-thickness tissue over a wide age range, compared with other gastrointestinal regions. Details are important because of natural human variability. We found age-related changes within the muscle, in the enteric and nociceptor innervation, and in the submucosa. Some involve all regions of colon, but the ascending colon appears more vulnerable. Changes can be cell- and sublayer-dependent. Mechanisms are unclear but may include development of "senescent-like" and associated inflammaging, perhaps associated with increased mucosal permeability to harmful luminal contents. In summary, reduced nociceptor innervation can explain diminished abdominal pain among the elderly. Degenerative changes within the colon wall may have little impact on symptoms and colonic functions, because of high "functional reserve," but are likely to facilitate the development of constipation during age-related challenges (e.g., lifestyle, disease, and medications), now operating against a reduced functional reserve.

Quadriceps Tendon Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients: 3-Year Clinical and Patient-Reported Outcomes.

The rate of anterior cruciate ligament (ACL) rupture in active, skeletally immature patients is increasing. Although hamstring tendon autograft (HTA) was previously deemed the gold standard, recent studies have shown HTA to have a high failure rate in this high-risk population of young competitive athletes, and quadriceps tendon autograft (QTA) has yielded excellent preliminary outcomes in some studies examining this population. To evaluate 3-year clinical and patient-reported functional outcomes of primary ACL reconstruction (ACLR) with soft tissue QTA in skeletally immature patients. Case series; Level of evidence, 4. Skeletally immature patients who underwent ACLR with a full-thickness soft tissue QTA were included. Preoperative patient and surgical data were collected. The ACLR technique was selected predicated upon skeletal age and included all-epiphyseal and complete transphyseal techniques. Patients were followed for a minimum of 2 years with successive clinical visits or were contacted via telephone. Patients who did not have minimum 2-year follow-up after 3 contact attempts via telephone were excluded. Information regarding return to sports (RTS) and concomitant or subsequent surgical procedures was collected. Pediatric International Knee Documentation Committee (Pedi-IKDC), Hospital for Special Surgery Functional Activity Brief Scale (HSS Pedi-FABS), and Single Assessment Numeric Evaluation (SANE) scores were collected. Of 85 adolescent patients aged 11.1 to 17.6 years (mean age, 14.1 ± 1.2 years), 2 patients were determined to be lost to follow-up after 3 failed contact attempts. Of the patients included in this study (N = 83), 26 patients (31%) underwent all-epiphyseal and 57 patients (69%) underwent complete transphyseal ACLR. Additionally, 48 patients (58%) underwent concomitant lateral extra-articular tenodesis using the iliotibial band with a modified Lemaire technique. The mean follow-up time was 3.7 ± 1.2 years (range, 2-7 years). Twenty (24%) patients had subsequent surgical procedures, of which 3 (4%) were due to graft failures. At a mean 3-year follow-up, the mean Pedi-IKDC, HSS Pedi-FABS, and SANE scores were 90, 23, and 94 respectively; the RTS rate was 100%; and the rate of RTS at the previous level of performance was 93%. Use of a soft tissue QTA for ALCR in a high-risk skeletally immature population of athletes resulted in excellent postoperative outcomes with low rates of graft failure and high return to sport rates.

Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery

BackgroundThe non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs.ResultsThe DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice.ConclusionResults obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.Graphical

Direct Subscarpal Lipectomy Combined With Liposuction in Abdominoplasty: An Analysis of Safety and Efficacy in 200 Consecutive Patients.

Abdominoplasty procedures continue to evolve because combining techniques such as suction-assisted lipectomy or direct subscarpal lipectomy have proven to be powerful adjuncts to achieve optimal aesthetic results. However, concern has been expressed about combining techniques simultaneously given the potential to damage the vascularity of the abdominoplasty flap. The aim of this study was to assess the safety and efficacy of simultaneous direct subscarpal lipectomy combined with liposuction in abdominoplasty patients. A 4-year retrospective review of consecutive abdominoplasties (n = 200) performed by a single surgeon was conducted. Liposuction of the abdominal flap and flanks was performed in all patients. After raising the abdominoplasty flap, undermining was performed to just beyond the xyphoid, the lower rib margins superiorly, and the anterior axillary line laterally. Fat deep to Scarpa's fascia was then removed by direct tangential excision in all zones of the abdominal flap. The patients had a mean age of 42.19 years and BMI of 28.10 kg/m2; the mean follow-up time was 7 months. Seroma occurred in 13 patients (6.5%), superficial wound dehiscence treated with local wound care in 16 patients (8%), hypertrophic scarring in 16 patients (8%), partial umbilical necrosis in 1 patient (0.5%), and partial umbilical epidermolysis in 6 patients (3%). No patients experienced major or minor full-thickness tissue loss. No patients needed reoperation. Simultaneous direct excision of subscarpal fat with liposuction of the abdomen and flanks does not appear to subject any zone of the abdominoplasty flap to increased risks of vascular compromise. No flap necroses were observed. The technique described is safe and may provide superior abdominoplasty results.

Large Penetrating Wounds to the Chest Managed With Immediate Chest Wall Reconstruction Using Biologic Mesh, Titanium Plates, and Rotational Tissue Flaps.

Large open chest wall wounds can be difficult to manage due to full-thickness tissue loss with underlying rib fractures and exposed lung parenchyma. Historically, the use of synthetic material has been discouraged in the traumatic setting with the concern that it may be associated with an increased risk of infection. We present 4 patients with large open injuries to the thorax-one from blunt and three from penetrating trauma. We describe our initial management followed by prompt surgical repair using biologic mesh, titanium rib spanning plates, and rotational tissue flaps with Z-plasty of the skin for definite closure. All patients did well post-operatively without complications or wound infections. With the appropriate management, we suspect there may be an advantage in performing immediate reconstruction and closure in large open thoracic injuries utilizing biologic mesh and titanium rib spanning plates with a lower risk of infection than previously believed.

Dehydration-Toughing Dual-Solvent Gels with Viscoelastic Transition for Infectious Wound Treatment.

The modulus of traditional biomedical hydrogels increases exponentially meditated by dehydration-stiffing mechanism, which leads to the failure of interface matching between hydrogels and soft tissue wounds. It is found in the study that the dual-solvent gels exhibit dehydration-toughening mechanism with the slowly increasing modulus that are always match the soft tissue wounds. Therefore, dual-solvent glycerol hydrogels (GCFen-gly DGHs) are prepared with hydrophobically modified catechol chitosan (hmCSC) and gelatin based on the supramolecular interactions. GCFen-gly DGHs exhibit excellent water retention capacity with a total solvent content exceeding 80%, permanent skin-like modulus within a range of 0.45 to 4.13kPa, and stable photothermal antibacterial abilities against S, aureus, E. coli, as well as MRSA. Infectious full-thickness rat skin defect model and tissue section analysis indicate that GCFen-gly DGHs are able to accelerate infectious wound healing by alleviating the inflammatory response, promoting granulation tissue growth, re-epithelialization, collagen deposition, and vascular regeneration. As a result, GCFen-gly DGHs is expected to become the next-generation biological gel materials for infectious wound treatment.

Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis

ObjectiveIntestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the...

Association of Quadriceps Tendon Harvest for ACL Reconstruction With Development of Osteochondritis Dissecans of the Patella in Pediatric Patients.

There are various reported complications after primary anterior cruciate ligament reconstruction (ACLR) necessitating additional surgery in skeletally immature patients, regardless of technique and autograft type. To analyze the rate and type of complications encountered with soft tissue quadriceps tendon autograft (QTA) for ACLR in patients ≤18 years as well as the overall rate of second surgery, unrelated to the use of the QTA. Case series; Level of evidence, 4. A total of 141 patients ≤18 years who underwent ACLR with a QTA and had minimum 6-month follow-up were included. All patients underwent ACLR by utilizing a full-thickness soft tissue QTA. Complications associated with the QTA harvest site and use of QTA were reported. The mean age of the included cohort (84 men, 57 women) was 14.8 ± 1.6 years. The average follow-up was of 2.0 ± 1.2 years. A total of 30 (21%) patients had a subsequent complication that required surgical intervention; in 11 (8%) patients, the complication was specifically associated with the use of a QTA, whereas in 19 (13%) patients, the complication was related to the ACLR. In addition, 13 (9%) patients underwent a contralateral ACLR procedure. Of the QTA-related complications, 2 patients developed osteochondritis dissecans (OCD)-like lesions in the superior aspect of the patella, 2 patients had injured their quadriceps extensor mechanism and required surgical repair, and 8 patients had a subsequent procedure to remove nonabsorbable sutures used for donor site quadriceps tendon closure. One of the patients who underwent the removal of nonabsorbable sutures also had an arthroscopic debridement of patellar chondral damage. We reported complications encountered with soft tissue QTA for ACLR. The complication rate for QTA harvest was 8%. However, given that the removal of nonabsorbable sutures from the donor site was caused by the surgical technique used, the revised nonsuture-related complication rate for QTA graft harvest was 2%. Although the use of a QTA has recently gained popularity due to its high return-to-sport and low graft-failure rates, surgeons should be aware of the complications associated with using this graft type.

P097 Spatially resolved insights into fistulating Crohn's disease pathogenesis: Unveiling molecular heterogeneity

Abstract Background Crohn's disease (CD) frequently results in fistula development in approximately 40% of patients due to sustained, transmural inflammation within the bowel wall. Despite advanced treatments, recurrence of fistulae affects one third of patients. Understanding its pathogenesis is crucial for targeted treatments, yet remains poorly defined. This study employs spatial transcriptomic and single-cell RNA-sequencing (scRNA-seq) technologies to characterise human fistulating CD tissue pathology. Methods Unbiased FFPE spatial transcriptomics (10x Visium) were applied to surgically resected, full-thickness (FT) tissue from 20 CD-associated fistulae cases and 15 controls. Subsequently, selected cases underwent further analysis using custom 500-plex MERFISH subcellular resolution spatial transcriptomics (Vizgen MERSCOPE). Additionally, a reference single-cell cohort encompassing patients with fistulating, stricturing, and inflammatory CD phenotypes, along with healthy controls, was generated. Optimisation of scRNA-seq for resected FT ileal tissue enabled the isolation and profiling of epithelial, immune, and stromal populations (10x Chromium). Computational analysis facilitated the spatial localisation of single-cell clusters enriched in fistula CD tissue, identifying key parameters linked to fistula development. Results The scRNA-seq data revealed diverse CD-specific cellular states adopted by intestinal fibroblasts, with IL11+ fibroblasts prominently expressing CD82, COL7A1, MMP1, CHI3L1, suggestive of pro-fibrotic signalling and regenerative morphogen pathways. This coincided with the expansion of a CD-specific subpopulation of pericytes (CCL19/CCL21) involved in leucocyte migration. Spatial profiling of CD fistula tracts by Visium and MERSCOPE unveiled an enrichment of key epithelial developmental transcription factors (e.g., GRHL3) and localised the pro-fibrotic signature displaying increased IL11 and MMP expression, along with perturbed WNT signalling within the fistula stroma. Active proliferation (HOPX, MKI67) was observed at the base of fistula tracts and within the stroma. Transcriptomic characterisation depicted a gradual loss in stem cell signature (LGR5, ASCL2, SMOC2) and supporting telocytes (POSTN) toward the leading edge of the fistula, signifying abnormal epithelium loss. Conclusion This pioneering study integrates multi-modal spatial transcriptomics and single-cell profiling to unveil the intricate cellular and molecular landscape in FT, fistulating CD pathology. Spatial analyses elucidate specific mechanisms involved in epithelial loss, stromal remodelling, and perturbed WNT signalling pathways within fistulating tissue, outlining a course of disrupted regenerative processes in fistulating CD.

Potential Role of Macrophage Polarization in the Progression of Hunner-Type Interstitial Cystitis.

Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.

Surgical Approach of Pleomorphic Dermal Sarcoma on the Scalp: A Case Report

Pleomorphic dermal sarcoma (PDS) is a fast-growing mesenchymal tissue tumor with similar characteristics to an atypical fibroxanthoma (AFX) presenting a significant clinical challenge to diagnose for physicians. We report a 79-year-old male presenting with a 3-month history of a lesion on his scalp that had been previously superficially biopsied yielding a diagnosis of PDS or AFX. Following a second biopsy, new findings led to the diagnosis of PDS. A wide local excision with 2 cm margin with delayed split-thickness skin graft reconstruction was performed. Treatment for PDS favors wide local excision with a 2–3 cm margin and adjuvant radiotherapy if perineural involvement. We support the following recommendations: full-thickness appropriate tissue diagnosis, pulmonary computed tomography scan, or X-ray to rule out metastasis, followed by a multidisciplinary team evaluation. These complex cases should be presented at a tumor board and tailored treatments should be based on patient risk factors and relevant history.

Frontal Flaps for Reconstruction of Nasal Defects

Nasal reconstruction is no longer just about filling in a nasal defect, it aims for an aesthetic and functional results. It is a three-dimensional reconstruction, restoring the mucosal plane, the osteo-cartilaginous architecture and the skin coverage to which Burget added a fourth dimension, the aesthetic result. Frontal flaps have been used for a very long time to repair nasal defects. Their popularity is mainly linked to their proximity to the recipient site, their good vascularization and especially the color and texture of the frontal skin which are significantly similar to those of the nasal skin. The frontal flap is the technique of choice in the reconstruction of full-thickness nasal tissue defects. We adopted the reconstruction by frontal flaps for the repair of multiple nasal defects, concerning multiple patients all treated at the plastic and aesthetic surgery department of the Mohammed VI University Hospital of Tangier over a period of 2 years going from March 2021 to March 2023. The goal of this study is to evaluate its contribution and answer the following question; What are the indications of using frontal flaps, its advantages and limitations in rhinopoiesis? and to draw practical recommendations regarding its use.

Assessment of the utility of the novel Phenion® full thickness human skin model for detecting the skin irritation potential of antimicrobial cleaning products

The skin is a potential route of exposure to antimicrobial cleaning products (ACP). Skin irritation, reversible damage to the skin, is an endpoint for protecting consumers and operators accidently exposed to these complex mixtures. To assess skin irritation of 24 ACP formulations, a new protocol was developed and adapted from OECD Test Guideline No. 439 with EpiDerm™ (epidermis model) replaced by Phenion® FT (full thickness tissue, including epidermis and dermis) as the test system. A full thickness tissue was utilized to provide a more human in vivo-like model. Formulations were applied to Phenion® FT and cell viability measured by MTT reduction after a 15-min exposure and 42 h post exposure period. A prediction model was applied, and results compared with in vivo rabbit skin irritation data. Concordance between in vivo and in vitro was demonstrated to be suitable (i.e., sensitivity 78%, specificity 83%, and accuracy 79%) using this modified OECD Test Guideline No. 439 method with a 70% cell viability selected as the most reasonable cut off for discriminating non-irritants (EPA Class IV). These results were considered suitable to develop a draft IATA i.e., with any ACP formulation identified as EPA Category IV in this test. The method will be further refined to distinguish irritant categories.

On-Site Construction of a Full-Thickness Skin Equivalent with Endothelial Tube Networks via Multilayer Electrospinning for Wound Coverage.

Novel full-thickness skin substitutes are of increasing interest due to the inherent limitations of current models lacking capillary networks. Herein, we developed a novel full-thickness skin tissue containing blood capillary networks through a layer-by-layer assembly approach using a handy electrospinning apparatus and evaluated its skin wound coverage potential in vivo. The average diameter and thickness of fabricated poly-ε-caprolactone-cellulose acetate scaffolds were easily tuned in the range of 474 ± 77-758 ± 113 nm and 9.43 ± 2.23-29.96 ± 5.78 μm by varying electrospinning distance and duration, as indicated by FE-SEM. Besides, keratinocytes exhibited homogeneous differentiation throughout the fibrous matrix prepared with electrospinning distance and duration of 9 cm and 1.5 min within five-layer (5L) epidermal tissues with thickness of 135-150 μm. Moreover, coculture of vascular endothelial cells, circulating fibrocytes, and fibroblasts within the 5L dermis displayed network formation in vitro, resulting in reduced inflammatory factor levels and enhanced integration with the host vasculature in vivo. Additionally, the skin equivalent grafts consisting of the epidermal layer, biomimetic basement membrane, and vascularized dermis layer with an elastic modulus of approximately 11.82 MPa exhibited accelerated wound closure effect indicative of re-epithelialization and neovascularization with long-term cell survival into the host, which was confirmed by wound-healing rate, bioluminescence imaging activity, and histological analysis. It is the first report of a full-thickness skin equivalent constructed using a battery-operated electrospinning apparatus, highlighting its tremendous potential in regenerative medicine.

Tailoring the Swelling-Shrinkable Behavior of Hydrogels for Biomedical Applications.

Hydrogels with tailor-made swelling-shrinkable properties have aroused considerable interest in numerous biomedical domains. For example, as swelling is a key issue for blood and wound extrudates absorption, the transference of nutrients and metabolites, as well as drug diffusion and release, hydrogels with high swelling capacity have been widely applicated in full-thickness skin wound healing and tissue regeneration, and drug delivery. Nevertheless, in the fields of tissue adhesives and internal soft-tissue wound healing, and bioelectronics, non-swelling hydrogels play very important functions owing to their stable macroscopic dimension and physical performance in physiological environment. Moreover, the negative swelling behavior (i.e., shrinkage) of hydrogels can be exploited to drive noninvasive wound closure, and achieve resolution enhancement of hydrogel scaffolds. In addition, it can help push out the entrapped drugs, thus promote drug release. However, there still has not been a general review of the constructions and biomedical applications of hydrogels from the viewpoint of swelling-shrinkable properties. Therefore, this review summarizes the tactics employed so far in tailoring the swelling-shrinkable properties of hydrogels and their biomedical applications. And a relatively comprehensive understanding of the current progress and future challenge of the hydrogels with different swelling-shrinkable features is provided for potential clinical translations.