EDTP enhances and protects the fluorescent signal of GFP in cleared and expanded tissues.

Advanced 3D high-resolution imaging techniques are essential for investigating biological challenges, such as neural circuit analysis and tumor microenvironment in intact tissues. However, the fluorescence signal emitted by endogenous fluorescent proteins in cleared or expanded biological samples gradually diminishes with repeated irradiation and prolonged imaging, compromising its ability to accurately depict the underlying scientific problem. We have developed a strategy to preserve fluorescence in cleared and expanded tissue samples during prolonged high-resolution three-dimensional imaging. We evaluated various compounds at different concentrations to determine their ability to enhance fluorescence intensity and resistance to photobleaching while maintaining the structural integrity of the tissue. Specifically, we investigated the impact of EDTP utilization on GFP, as it has been observed to significantly improve fluorescence intensity, resistance to photobleaching, and maintain fluorescence during extended room temperature storage. This breakthrough will facilitate extended hydrophilic and hydrogel-based clearing and expansion methods for achieving long-term high-resolution 3D imaging of cleared biological tissues by effectively safeguarding fluorescent proteins within the tissue.

Endoscopic Tissue Expander Implantation in Post-Burn Reconstruction: A Review of the Literature.

BACKGROUND: Tissue expansion generates new tissue that can be used in post-burn reconstruction. Expanders are placed through small incisions, requiring difficult and sometimes blind dissection to prepare an adequate pocket. Recently, the use of endoscopy to assist in expander placement has been described, which may improve intraoperative visualization and allow for a smaller incision. In this review, we summarize the existing literature of endoscopic tissue expander (TE) placement in post-burn reconstruction and highlight areas for future research. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were utilized to conduct this review. The following databases were queried for the initial search of relevant articles: PubMed, Embase, Scopus, Cochrane, and Web of Science. The data was assessed qualitatively due to the heterogeneity in reporting between the studies. RESULTS: Our literature query yielded 1,023 studies. Sixteen manuscripts underwent full-text review, and seven met inclusion criteria. All studies demonstrated that the endoscopic approach led to successful tissue expansion. Four articles performed a comparative analysis between the open and endoscopic approach, all of which found a significant reduction in complications like seroma, hematoma formation, and device exposure with endoscopic TE implantation. Two studies demonstrated that the use of endoscopy significantly reduced operative time and length of stay. CONCLUSION: Endoscopy is a safe and effective tool in tissue expansion for post-burn reconstruction. Further prospective research should include evaluating the cost-benefit of this approach and long-term outcomes for patients who have undergone endoscopic-assisted tissue expander placement.

Reconstructive techniques for radiation-induced hemifacial sequelae: A hemangioma case study.

INTRODUCTION AND IMPORTANCE: The use of radiation therapy for infantile hemangiomas 30 years ago has led to severe consequences in adulthood. CASE PRESENTATION: This article shares the experience of using multiple reconstructive procedures to treat radiation-induced hemifacial sequelae for capillary malformations. Based on the damaged anatomical surgical units, appropriate reconstructive materials are used for the surgery. Thin antero-lateral thigh (ALT) flaps cover lesions on the forehead and cheeks, while a skin expander covers the temporal scalp lesion. Autologous grafting covers damage in both eyelids. CLINICAL DISCUSSION: Choosing a suitable reconstructive material will provide aesthetic outcomes such as facial symmetry, skin color compatibility, and textural similarity in the constructive areas for the patient. The patients were highly satisfied with the surgical results. CONCLUSION: Using appropriate surgical techniques and materials, along with meticulous attention to facial integrity, can achieve optimal aesthetic and functional outcomes in patients with severe facial disfigurement from radiation therapy. A thorough understanding of pathophysiology and anatomy, along with skillful execution, can result in a successful outcome and improved quality of life.

Aesthetic Reconstruction of the Sequelae of Large Facial Involuted Infantile Hemangioma with Tissue Expanders.

BACKGROUND: Large involuted infantile hemangioma remains a challenge in facial reconstruction. The characteristic fibrofatty residuum and multiple subunits/tissues involvement contribute significantly to the difficulty of surgical management. Tissue expander plays an important role in facial reconstruction, allowing plastic surgeons to repair skin damaged by both congenital and acquired defects. METHODS: Between 2009 and 2021, 30 patients who underwent tissue expansion surgery were reviewed in a single hospital. The demographic data, lesion characteristics, surgical approaches, complication rate, and aesthetic outcomes were analyzed. RESULTS: Thirty patients (5 men and 25 women) with a mean age of 14.03 ± 7.25 years (range, 4-33 years) were included. The mean follow-up is 35.92 months, ranging from 9 to 75 months. Tissue expansion-related complications include closed infection, 2/30 (6.67%); skin ischemia, 2/30 (6.67%); hematoma, 1/30 (3.33%); flap necrosis, 1/30 (3.33%). CONCLUSION: Large facial involuted infantile hemangiomas have variable patterns of presentation and necessitate tailored therapy. Tissue expansion is a reproducible approach to achieving aesthetic reconstruction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Serial Tissue Expansion and Skin Grafts in the Management of a Giant Congenital Nevus of the Face: Review of Literature and Case Report.

Giant congenital nevi, especially on the head and neck, pose a challenge for plastic surgeons. This requires extensive experience in detailed planning, combining different techniques, and selecting appropriate materials for reconstruction. There have been reports of using a tissue expander, serial resection method, and full-thickness skin grafts for this type of nevus. However, the best way to completely remove a giant congenital nevus is endless. In this article, we would like to present a case of a left hemifacial giant congenital nevus in which we used multiple tissue expansion to fully replace the nevus, along with some of our modification techniques.

Pediatric Facial Burn Reconstruction.

Contrary to prior pediatric burn treatment philosophies, we now know that early burn excision and grafting for non life-threatening burns can compromise future reconstruction. Extensive scar excision should be minimized and scar rehabilitation maximized, as secondary iatrogenic deformities can become even more difficult to fix. Scar remodeling with local tissue rearrangement can relieve tension and soften scars over time. The majority of facial burns often only involve skin and can be adequately treated without the need for complex flap reconstruction. Facial burn scars are a different problem than facial burn scar contracture. The former needs scar rehabilitation, whereas the latter needs the addition of skin. Laser therapy has transformed the treatment of burn scars and is an incredibly valuable adjunct to local tissue rearrangement and grafting. The most favorable functional, aesthetic, and psychological outcomes require a long-term multidisciplinary effort and customized protocol utilizing the vast armamentarium of reconstructive tools described below.

Deletion of Impdh2 in adipocyte precursors limits the expansion of white adipose tissue and enhances metabolic health with overnutrition.

The equilibrium between the hypertrophic growth of existing adipocytes and adipogenesis is vital in managing metabolic stability in white adipocytes when faced with overnutrition. Adipogenesis has been established as a key player in combating metabolic irregularities caused by various factors. However, the benefits of increasing adipogenesis-mediated white adipose tissue (WAT) expansion for metabolic health regulation remain uncertain. Our findings reveal an increase in Impdh2 expression during the adipogenesis phase, both in vivo and in vitro. Xmp enhances adipogenic potential by fostering mitotic clonal expansion (MCE). The conditional knockout of Impdh2 in adipocyte progenitor cells(APCs) in adult and aged mice effectively curbs white adipose tissue expansion, ameliorates glucose tolerance, and augments energy expenditure under high-fat diet (HFD). However, no significant difference is observed under normal chow diet (NCD). Concurrently, the knockout of Impdh2 in APCs significantly reduces the count of new adipocytes induced by HFD, without affecting adipocyte size. Mechanistically, Impdh2 regulates the proliferation of APCs during the MCE phase via Xmp. Exogenous Xmp can significantly offset the reduction in adipogenic abilities of APCs due to Impdh2 deficiency. In summary, we discovered that adipogenesis-mediated WAT expansion, induced by overnutrition, also contributes to metabolic abnormalities. Moreover, the pivotal role of Impdh2 in regulating adipogenesis in APCs offers a novel therapeutic approach to combat obesity.

A machine learning approach to predict in vivo skin growth.

Since their invention, tissue expanders, which are designed to trigger additional skin growth, have revolutionised many reconstructive surgeries. Currently, however, the sole quantitative method to assess skin growth requires skin excision. Thus, in the context of patient outcomes, a machine learning method which uses non-invasive measurements to predict in vivo skin growth and other skin properties, holds significant value. In this study, the finite element method was used to simulate a typical skin expansion protocol and to perform various simulated wave propagation experiments during the first few days of expansion on 1,000 individual virtual subjects. An artificial neural network trained on this dataset was shown to be capable of predicting the future skin growth at 7 days (avg. R2 = 0.9353) as well as the subject-specific shear modulus (R2 = 0.9801), growth rate (R2 = 0.8649), and natural pre-stretch (R2 = 0.9783) with a very high degree of accuracy. The method presented here has implications for the real-time prediction of patient-specific skin expansion outcomes and could facilitate the development of patient-specific protocols.

Superficial Temporal Artery Island Flap Combined With Laser Hair Removal for Inadequate Skin Expansion Following Tissue Expansion: A Case Report of Congenital Melanocytic Nevus of the Forehead in an Adult.

Tissue expansion is a handy reconstructive technique for the head and neck region; however, its implementation requires careful planning and surgical experience. If tissue expansion is inadequate, forced closure results in wound tension and risks complications, such as postoperative deformity, wide scarring, and wound dehiscence. We report a case of adult forehead melanocytic nevus excision using a tissue expander (TE) where complications caused by insufficient tissue expansion were avoided by creating a flap using a dog ear. The patient was a male in his 20s who underwent surgery with a TE for a congenital melanocytic nevus sized 15 × 10 cm on the left forehead. Resection was performed by tissue expansion using two TEs; however, simple advancement flaps led to excessive wound tension, risk of elevation of the eyebrow on the affected side, and postoperative scarring. Hence, a superficial temporal artery fasciocutaneous island flap with left superficial temporal vessels as a pedicle was raised at the dog ear and moved to the site of strong tension, and the wound was closed without difficulty. Although postoperative laser hair removal was required, both the appearance and functional results were satisfactory. Using anatomical flaps obtained from the surroundings during tissue expansion helps avoid complications associated with forced wound closure.

Dynamic alterations in M2 macrophage subtypes enhance flap expansion efficiency and tissue regeneration.

Dilatation of soft skin tissue is a common surgical procedure in plastic surgery. M2 macrophages play a critical role in reducing inflammation, promoting epithelial and vascular endothelial cell proliferation, enhancing collagen synthesis in fibroblasts, and orchestrating extracellular matrix remodelling by promoting angiogenesis, epithelialisation, and fibrosis. Macrophages improve flap survival by promoting microangiogenesis and collagen remodelling. However, the role of macrophages in flap expansion has not yet been investigated. Improving the expansion efficiency of dilatation flaps and promoting flap vascularisation are the pressing problems in the fields of plastic and reconstruction surgery. In the present study, we used a mouse model to assess the effects of macrophage activation on skin expansion, thickness, ultrastructure, intradermal angiogenesis, and collagen and cytokine levels. Our findings revealed dynamic changes in the macrophage content and subtypes within the expansion flaps. The enrichment of M2 macrophages significantly enhanced the efficiency of flap expansion, vascularisation, and collagen synthesis. Our findings underline the pivotal role of M2 macrophages in tissue regeneration at the molecular and biochemical levels. These findings provide a basis for improving flap expansion efficiency using M2 macrophages.

Hair follicle stem cells promote epidermal regeneration under expanded condition.

Skin soft tissue expansion is the process of obtaining excess skin mixed with skin development, wound healing, and mechanical stretching. Previous studies have reported that tissue expansion significantly induces epidermal proliferation throughout the skin. However, the mechanisms underlying epidermal regeneration during skin soft tissue expansion are yet to be clarified. Hair follicle stem cells (HFSCs) have been recognized as a promising approach for epidermal regeneration. This study examines HFSC-related epidermal regeneration mechanisms under expanded condition and proposes a potential method for its cellular and molecular regulation.

Flap Advancement Technique for Scalp Hair Preservation in Massive Cutis Verticis Gyrata.

Cutis verticis gyrata (CVG) is a rare skin condition characterized by ridges and furrows resembling the brain. CVG falls under three categories: primary essential, primary nonessential, and secondary. This case report focuses on primary essential CVG, where approximately a fourth of the scalp and a significant portion of the forehead and eyelid were involved. Flap advancement after skin expansion was performed to rectify the disorder. This technique adequately covers the residual defect postexcision and preserves hair growth in affected regions. It is a successful skin expansion technique to cover the exposed scalp, preserve hair growth, and achieve excellent cosmetic results. Our approach demonstrates a promising solution for severe cosmetic disfigurement in primary essential CVG, positively impacting both the physical appearance and psychosocial well-being of the patient.

The Effects of Negative Pressure Therapy on Hair Growth of Mouse Models.

Negative pressure therapy (NPT) has been shown to facilitate wound healing and promote hair growth in a porcine model. However, there is a paucity of research on the impact of negative pressure on hair growth in murine models. Despite the ability of nude mice to develop hair follicles, the hair they produce is often flawed towing to genetically induced keratin disorders, rendering them a pertinent animal model for assessing hair regeneration. Therefore, this study aims to investigate the effects of negative pressure on hair follicle growth in a nude mouse model. To achieve this, a customized external tissue expansion device was developed to apply negative pressure to the dorsum of nude mice. The mice were subjected to several treatment courses consisting of 15 and 30 min of continuous negative pressure at 10 mmHg, which were repeated 5 and 10 times every other day until sacrifice. Dorsal skin samples were subsequently extracted from the suction and nonsuction areas. The sections were stained with various antibodies to assess the expression of SOX-9, LHX-2, Keratin-15, ß-catenin, CD31, and vascular endothelial growth factor-A, and a TUNEL assay was used to analyze cell apoptosis. The results showed that the number of hair follicles and angiogenesis were significantly higher in the suction area than in the nonsuction area in all groups. Moreover, mice that received NPT for 15 min for 10 times had a higher hair follicle density than the other three groups. Immunofluorescence staining for LHX-2 and Keratin 15 further validated the results of these findings. In conclusion, this study demonstrated that negative pressure effectively promotes hair follicle growth and angiogenesis in nude mice through SOX-9- and LHX-2-mediated follicular regeneration and ß-catenin-mediated hair follicle morphogenesis.

Prediction model for haematoma after tissue expander placement: A retrospective cohort study of 7080 cases over 20 years.

Haematoma is an early complication of tissue expander placement and can lead to infection, capsule contracture and various complications, hindering successful reconstruction. However, no scientific models can accurately predict the risk of haematoma following tissue expansion. Therefore, this study aimed to develop and validate a prediction model for haematoma following tissue expander placement. The medical records of patients who underwent expander placement between 2001 and 2021 were obtained from the clinical database of the Department of Plastic Surgery at the Xijing Hospital. A total of 4579 consecutive patients with 7080 expanders and 179 expanded pocket haematomas were analysed. Multivariate logistic regression analysis identified adult age (P = 0.006), male sex (P < 0.001), scar reconstruction (P = 0.019), perioperative hypertension (P < 0.001), face and neck location (P = 0.002) and activated partial thromboplastin time above the normal range (P < 0.001) as risk factors for haematoma. Therefore, these were included in the prediction model, and a nomogram was constructed. The discrimination of the nomogram was robust (area under the curve: 0.78; 95% confidence interval: 0.72-0.83). Further, the prediction model had a strong fit (Hosmer-Lemeshow test, P = 0.066) and maintained similar discrimination after considering performance optimism (bootstrapped area under the curve: 0.79; 95% confidence interval: 0.73-0.84). This clinical prediction model was created using a generalisable dataset and can be utilised to obtain valid haematoma predictions after expander placement, assisting surgeons in implementing preventive measures or interventions to reduce the occurrence of haematoma.

A perioperative layered autologous tissue expansion graft for hollow organ repair.

Tissue engineering has not been widely adopted in clinical settings for several reasons, including technical challenges, high costs, and regulatory complexity. Here, we introduce the Perioperative Layered Autologous Tissue Expansion graft (PLATE graft), a composite biomaterial and collagen-reinforced construct with autologous epithelium on one side and smooth muscle tissue on the other. Designed to mimic the structure and function of natural hollow organs, the PLATE graft is unique in that it can be produced in a standard operating theatre and is cost-effective. In this proof-of-principle study, we test its regenerative performance in eight different organs, present biomechanical and permeability tests, and finally explore its in vivo performance in live rabbits.

Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion.

Background: Tissue expansion, a technique in which skin regeneration is induced by mechanical stretch stimuli, is commonly used for tissue repair and reconstruction. In this study, we aimed to monitor the autophagy levels of expanded skin after the application of expansion stimuli and explore the effect of autophagy modulation on skin regeneration. Methods: A rat scalp expansion model was established to provide a stable expanded skin response to mechanical stretch. Autophagy levels at different time points (6, 12, 24, 48 and 72 h after the last expansion) were detected via western blotting. The effect of autophagy regulation on skin regeneration during tissue expansion was evaluated via skin expansion efficiency assessment, western blotting, immunofluorescence staining, TUNEL staining and laser Doppler blood flow imaging. Results: The autophagic flux reached its highest level 48 h after tissue expansion. Activating autophagy by rapamycin increased the area of expanded skin as well as the thicknesses of epidermis and dermis. Furthermore, activating autophagy accelerated skin regeneration during tissue expansion by enhancing the proliferation of cells and the number of epidermal basal and hair follicle stem cells, reducing apoptosis, improving angiogenesis, and promoting collagen synthesis and growth factor secretion. Conversely, the regenerative effects were reversed when autophagy was blocked. Conclusions: Autophagy modulation may be a promising therapeutic strategy for improving the efficiency of tissue expansion and preventing the incidence of the complication of skin necrosis.

Single versus Double Drainage for Immediate Two-Stage Implant-Based Breast Reconstruction: A Propensity Score-Matched Analysis.

BACKGROUND: Reports evaluating plastic surgeons' practices indicate there are conflicting trends regarding the use of one or two drains for implant-based breast reconstruction (IBBR). Our study aimed to perform a matched cohort analysis to examine the postoperative outcomes and complications of immediate IBBR with tissue expander (TE) using two drains versus a single drain. METHODS: A propensity score-matched analysis (nearest neighbor, 1:1 matching) of immediate reconstructions using two versus one drain was conducted. Female patients undergoing immediate two-stage IBBR with TEs between January 2011 and May 2021 were included. The covariables were as follows: BMI, mastectomy weight, lymph node surgery, TE surface, plane of reconstruction, use of acellular dermal matrix products, fluorescence imaging use, and intraoperative TE volume. RESULTS: After matching using propensity scores, 192 reconstructions were included in the final analysis: 96 in each group. The rate of 30-day complications and overall complications during the first phase of IBBR were comparable between groups. The time for drain removal, time to initiate and finalize expansions, and time for TE-to-implant exchange were comparable between groups. Diabetes (OR 3.74, p = 0.025) and an increased estimated blood loss (OR 1.004, p = 0.01) were the only independent predictors for seroma formation. CONCLUSION: In this matched cohort analysis evaluating the role of one versus two drains for two-stage IBBR, we found a comparable rate of complications and surgical outcomes between the two cohorts. Using two drains for immediate IBBR needs to be tailored depending on intraoperative findings. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment for benign skin lesion in zygomatic-infraorbital region by the expanded multi-lobe cervicofacial advancement rotation flap in pediatric patients.

PURPOSE: Benign skin lesions in zygomatic-infraorbital regions severely influence pediatric patients' appearance as well as mental health. Treatments are difficult for the high requirements of patients' guardians in both function and aesthetics. The present study aims to introduce a surgical method, Expanded Multi-Lobe Cervicofacial Flap, which combines the advantages of the classical cervicofacial advancement rotation flap and the tissue expansion technique. METHODS: A total of 21 pediatric patients were enrolled. The treatment process included 2 stages: implantation of the skin tissue expander and flap transfer. The excessive skin created by tissue expansion extended the coverage area of the multi-lobe flap. RESULTS: In this retrospective study, follow-up periods were all more than 12 months (20.8 ± 6.7). In the last follow-ups, the flaps were all in good condition, and No facial organ displacement was observed. The patients' guardians were satisfied with the outcomes. CONCLUSIONS: Using the expanded multi-lobe cervicofacial flap for the zygomatic-infraorbital benign skin lesion repair is effective, and this method is especially applicable to the pediatric population.

CT-based evaluation of tissue expansion in cryoablation of ex vivo kidney.

OBJECTIVES: To evaluate tissue expansion during cryoablation, the displacement of markers in ex vivo kidney tissue was determined using computed tomographic (CT) imaging. METHODS: CT-guided cryoablation was performed in nine porcine kidneys over a 10 min period. Markers and fiber optic temperature probes were positioned perpendicular to the cryoprobe shaft in an axial orientation. The temperature measurement was performed simultaneously with the acquisitions of the CT images in 5 s intervals. The distance change of the markers to the cryoprobe was determined in each CT image and equated to the measured temperature at the marker. RESULTS: The greatest increase in the distance between the markers and the cryoprobe was observed in the initial phase of cryoablation. The maximum displacement of the markers was determined to be 0.31±0.2 mm and 2.8±0.02 %, respectively. CONCLUSIONS: The mean expansion of ex vivo kidney tissue during cryoablation with a single cryoprobe is 0.31±0.2 mm. The results can be used for identification of basic parameters for optimization of therapy planning.

S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion.

Background: In plastic surgery, tissue expansion is widely used for repairing skin defects. However, low expansion efficiency and skin rupture caused by thin, expanded skin remain significant challenges in promoting skin regeneration during expansion. S100 calcium-binding protein A9 (S100A9) is essential in promoting wound healing; however, its effects on skin regeneration during tissue expansion remain unclear. The aim of the present study was to explore the role of S100A9 in skin regeneration, particularly collagen production to investigate its importance in skin regeneration during tissue expansion. Methods: The expression and distribution of S100A9 and its receptors-toll-like receptor 4 (TLR-4) and receptor for advanced glycation end products were studied in expanded skin. These characteristics were investigated in skin samples of rats and patients. Moreover, the expression of S100A9 was investigated in stretched keratinocytes in vitro. The effects of S100A9 on the proliferation and migration of skin fibroblasts were also observed. TAK-242 was used to inhibit the binding of S100A9 to TLR-4; the levels of collagen I (COL I), transforming growth factor beta (TGF-ß), TLR-4 and phospho-extracellular signal-related kinase 1/2 (p-ERK1/2) in fibroblasts were determined. Furthermore, fibroblasts were co-cultured with stretched S100A9-knockout keratinocytes by siRNA transfection and the levels of COL I, TGF-ß, TLR-4 and p-ERK1/2 in fibroblasts were investigated. Additionally, the area of expanded skin, thickness of the dermis, and synthesis of COL I, TGF-ß, TLR-4 and p-ERK1/2 were analysed to determine the effects of S100A9 on expanded skin. Results: Increased expression of S100A9 and TLR-4 was associated with decreased extracellular matrix (ECM) in the expanded dermis. Furthermore, S100A9 facilitated the proliferation and migration of human skin fibroblasts as well as the expression of COL I and TGF-ß in fibroblasts via the TLR-4/ERK1/2 pathway. We found that mechanical stretch-induced S100A9 expression and secretion of keratinocytes stimulated COL I, TGF-ß, TLR-4 and p-ERK1/2 expression in skin fibroblasts. Recombined S100A9 protein aided expanded skin regeneration and rescued dermal thinning in rats in vivo as well as increasing ECM deposition during expansion. Conclusions: These findings demonstrate that mechanical stretch promoted expanded skin regeneration by upregulating S100A9 expression. Our study laid the foundation for clinically improving tissue expansion using S100A9.