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.

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.

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.

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.

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.

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.

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.

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 .

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.

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.

Hydrogel based soft tissue expanders for orodental reconstruction.

Tension-free flap closure to prevent soft tissue dehiscence is a prerequisite for successful bone augmentation in orodental reconstructive surgery. Since soft tissue contour follows the underlying jaw bony architecture, resorption of alveolar (jaw) bone limits the availability of soft tissue for wound closure following major bone reconstruction, required to facilitate oral rehabilitation with endosseous dental implants following tooth loss. Although there are several clinical procedures to increase soft tissue volume, these techniques are complicated and technically demanding. Soft tissue expansion, an established technique in reconstructive surgery, is an ideal alternative to generate surplus soft tissue prior to bone augmentation and dental implant placement. Increase in tissue volume can be achieved by using soft tissue expanders (STEs). Contemporary STEs have evolved from silicone balloons to osmotically inflating hydrogel-based systems. Here, we provide an overview of STEs in clinical oral surgery, outline the current research in STEs, and an update on recent clinical trials as well as the associated complications. Also, the mechanism governing soft tissue expansion and the critical factors that control the expansion process are covered. Design considerations for STEs for intraoral applications are given particular attention. Finally, we present our perspectives on utilization of minimally invasive methods to administer STEs for orodental applications. STATEMENT OF SIGNIFICANCE: Soft tissue expansion is required for a range of reconstructive applications and more notably in regenerative dentistry for vertical bone augmentation. This review describes the commercially available soft tissue expanders along with the latest systems being currently developed. This review insightfully discusses the biological and physical mechanisms leading to soft tissue expansion and critically assesses the design criteria of soft tissue expanders. A particular focus is given on the development of a new generation of hydrogel-based soft tissue expanders; their chemistry and required physical properties for tissue expansion is described and the obstacles towards clinical translations are identified. Finally, the review elaborates on promising minimally invasive injectable hydrogel-based tissue expanders and highlights the beneficial features of these systems.

Diploid mycelia of Ustilago esculenta fails to maintain sustainable proliferation in host plant.

Smut fungi display a uniform life cycle including two phases: a saprophytic phase in vitro and a parasitic phase in host plants. Several apathogenic smut fungi are found, lacking suitable hosts in their habitat. Interestingly, MT-type Ustilago esculenta was found to maintain a parasitic life, lacking the saprophytic phase. Its long period of asexual proliferation in plant tissue results in severe defects in certain functions. In this study, the growth dynamics of U. esculenta in plant tissues were carefully observed. The mycelia of T- and MT-type U. esculenta exhibit rapid growth after karyogamy and aggregate between cells. While T-type U. esculenta successfully forms teliospores after aggregation, the aggregated mycelia of MT-type U. esculenta gradually disappeared after a short period of massive proliferation. It may be resulted by the lack of nutrition such as glucose and sucrose. After overwintering, infected Zizania latifolia plants no longer contained diploid mycelia resulting from karyogamy. This indicated that diploid mycelia failed to survive in plant tissues. It seems that diploid mycelium only serves to generate teliospores. Notably, MT-type U. esculenta keeps the normal function of karyogamy, though it is not necessary for its asexual life in plant tissue. Further investigations are required to uncover the underlying mechanism, which would improve our understanding of the life cycle of smut fungi and help the breeding of Z. latifolia.

Predictors for Prolonged TE-to-Implant Exchange During Implant-Based Breast Reconstruction: A Single Institution Experience.

BACKGROUND: There is limited evidence regarding the factors causing a prolonged time for tissue expander (TE) exchange into a definitive implant using two-stage implant-based breast reconstruction (IBBR). This study aimed to review our experience with IBBR, focusing on the time for TE-to-implant exchange and determining which factors cause a prolonged time for exchange. METHODS: A retrospective review was performed to include women undergoing immediate two-stage IBBR with TEs after total mastectomy between January 2011 and May 2021. Reconstructions with irradiated TEs were excluded. Cases that had a prolonged time for TE-to-implant exchange were defined as those undergoing exchange longer than 232 days, which corresponds to the 75th percentile of the overall study group. RESULTS: We included 442 reconstructions in our analysis. The median age for our series was 51 years and the median body mass index was 26.43-kg/m2. The median time for TE-to-implant exchange was 155 days [IQR, 107-232]. Cases that had a prolonged time for TE-to-implant exchange were defined as those undergoing exchange on postoperative day 232 or afterward. Diabetes (OR 4.05, p = 0.006), neoadjuvant chemotherapy (OR 2.76, p = 0.006), an increased length of stay (OR 1.54, p = 0.013), and a lengthier time to complete outpatient expansions (OR 1.018, p < 0.001) were independently associated with a prolonged time for exchange. CONCLUSION: As evident from our analysis, the time for exchange is highly heterogeneous among patients. Although several factors affect the timing for TE-to-implant exchange, efforts must be directed to finalize outpatient expansions as soon as possible to expedite the transition into a definitive implant. 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 .

The use of abdominal wall tissue expansion prior to herniorrhaphy in massive ventral hernia defects.

BACKGROUND: Massive ventral hernias pose a challenging reconstructive problem. In comparison to bridging mesh repair, the primary fascial repair is associated with significantly reduced rates of hernia recurrence. This study will review our experience with massive ventral hernia repairs using tissue expansion and anterior component separation as well as present the largest case series to date. METHODS: A retrospective review was conducted of 61 patients who underwent abdominal wall tissue expansion prior to herniorrhaphy at a single institution between 2011 and 2017. Demographics, perioperative co-variates, and outcomes were recorded. Univariate and subgroup analysis was performed. Kaplan-Meier survival analysis was used to assess the time to recurrence. RESULTS: Sixty-one patients underwent abdominal wall expansion via tissue expanders (TE). Of these, 56 subsequently underwent staged anterior component separation for attempted closure of large ventral hernia. Major complications of TE placement included TE replacement (4,6.6%), TE leak (2,3.3%), and unplanned readmission (3,4.9%). Higher BMI groups were significantly associated with comorbid hypertension (BMI<30 kg/m2, 22.7%; BMI 30-35 kg/m2, 68.7%; BMI>35 kg/m2, 64.7%; P = 0.004). 15 patients (32.6%) had hernia recurrence and 21 patients (34.4%) still required bridging mesh during herniorrhaphy after tissue expansion. CONCLUSION: The use of tissue expansion prior to herniorrhaphy can be effective in achieving durable closure for most massive abdominal wall defects - especially those associated with musculofascial, soft tissue, or skin deficiencies. In this proof-of-concept analysis, we found that the efficacy and safety profile of this technique compares favorably to other methods for massive hernia repair in the literature.

Nasal reconstruction with the expanded forehead flap: Long-term follow-up of esthetic outcome and 12-year experience.

BACKGROUND: The expanded forehead flap has its unique advantage in nasal reconstruction. The authors present their 12-year experience with nasal reconstruction with an expanded forehead flap. The esthetic and functional outcomes were assessed with long-term subjective and objective evaluations. METHODS: A retrospective analysis was conducted of consecutive patients who underwent nasal reconstruction with the expanded forehead flap from 2009 to 2021 performed by the senior author (F.F.). Data were collected and analyzed regarding defect characteristics, processes of treatment, and complications. Subjective esthetic and functional outcomes were assessed through questionnaires FACE-Q (Face Questionnaire) and NOSE (Nasal Obstruction Symptom Evaluation). The objective esthetic outcome was assessed by a senior resident through the viewing of clinical photographs. RESULTS: One hundred and fifty-five patients underwent nasal reconstruction with an expanded forehead flap. The average expansion period was 174 days, and the injection volume was 685.7 ml. There were 15 complications. One hundred and eight patients (69.6%) were satisfied, and 19 patients (12.2%) were very satisfied with the outcome. The differences between postoperative and preoperative scores of FACE-Q were statistically significant (p < 0.01). Sixty-nine percent of patients complained of bilateral eyebrow asymmetry, 27.1% of patients reported partial recovery of frontal deformity with dissatisfaction, and 2.6% of patients considered not recovered at all. The results of 78 patients (50.3%) were considered "satisfied," and 41 patients (26.5%) were considered "very satisfied" by objective evaluation. CONCLUSION: Nasal reconstruction with an expanded forehead flap was a safe technique with good esthetic outcomes. Although problems with the asymmetry of the eyebrows and frontal deformation were presented, the influence was minimal and well-accepted by most patients.

Molecular Decrowding by Tissue Expansion Allows Precise Determination of the Spatial Distribution of Synaptic Proteins at a Nanometer Scale by exTEM.

To understand how the molecular machinery of synapses works, it is essential to determine an inventory of synaptic proteins at a subsynaptic resolution. Nevertheless, synaptic proteins are difficult to localize because of the low expression levels and limited access to immunostaining epitopes. Here, we report on the exTEM (epitope-exposed by expansion-transmission electron microscopy) method that enables the imaging of synaptic proteins in situ. This method combines TEM with nanoscale resolution and expandable tissue-hydrogel hybrids for enhanced immunolabeling with better epitope accessibility via molecular decrowding, allowing successful probing of the distribution of various synapse-organizing proteins. We propose that exTEM can be employed for studying the mechanisms underlying the regulation of synaptic architecture and function by providing nanoscale molecular distribution of synaptic proteins in situ. We also envision that exTEM is widely applicable for investigating protein nanostructures located in densely packed environments by immunostaining of commercially available antibodies at nanometer resolution.

Macrophage contribution to the survival of transferred expanded skin flap through angiogenesis.

Background: Despite the application of tissue expansion in the reconstruction of significant tissue defects, complications with expanded random-pattern skin flaps remain a major challenge. Insufficient angiogenesis is one of the keys factors in flap ischemia and dysfunction. Macrophages play a key role in promoting tissue angiogenesis, but their effects on expanded flap angiogenesis and the survival of the transferred skin flap are still unknown. Methods: A rat scalp expansion model was established to evaluate the dynamic changes of macrophages in expanded skin. Clodronate liposomes (Clo-lipo) were injected into the expanded scalps to deplete the macrophages, and the expanded scalp flaps with macrophage depletion were orthotopically transferred. The remaining expanded rat scalp flaps were treated with either a macrophage-colony stimulating factor (M-CSF) alone or M-CSF in combination with Clo-lipo and transferred. The number of macrophages, blood perfusion, microvascular densities (MVDs), flap survival, histological changes, and gene expression related to macrophage polarization and angiogenesis were determined with immunofluorescence (IF) staining, full-field laser perfusion imager, hematoxylin and eosin (HE) staining, and quantitative real-time polymerase chain reaction. Results: The number of pan-macrophages significantly increased in the expanded scalp on days 14 and 21 after expander placement. The depletion rate after treatment with Clo-lipo was 29.06%, and the number of macrophages was significantly reduced in the group that underwent Clo-lipo treatment on day 14 before flap transfer (P<0.05). Macrophage depletion resulted in decreased blood perfusion, reduced MVDs, lower expression of factors, and poor survival rate. The recruitment of macrophages with a M-CSF led to higher blood perfusion, increased MVDs, greater expression of angiogenic factors, and better flap survival after flap transfer. Conclusions: Alternatively activated macrophages in the expanded flap could significantly promote angiogenesis, improve blood perfusion, and ultimately increase the flap survival rate. Modulating alternatively activated macrophages may provide a key therapeutic strategy to promote expanded skin flap survival. Our study has provided a basis for clinically improving random-pattern skin flap survival.

Tissue expansion techniques in reconstructive surgery: a 10-year bibliometric analysis.

Background: Tissue expansion (TE) has attracted significant attention from researchers over the past decade. However, there are currently no bibliometric analyses in this field. We aimed to quantitatively and visually analyze the literature to explore the hotspots and frontiers in TE research. Methods: We extracted all the documents on this topic published from the Web of Science Core Citation (WOSCC) database between 2012 and 2021. CiteSpace (version 5.8 R3) and VOSviewer (version 1.6.18) were used to perform the visualization analysis. Results: A total of 1,085 documents were included in the analysis. The publication trend fluctuated over time. The United States led the research, and Harvard University was the most productive institution. Plastic and Reconstructive Surgery published the largest number of documents and had the most citations. Kim JYS was the most prolific and most cited author. The high-frequency keywords were "complications", "breast reconstruction", "outcomes", "tissue expander", "mastectomy", and "acellular dermal matrix" (ADM). "Surgical site infection", "tissue expander/implant", "bilateral prophylactic mastectomy", and "activated controlled expansion" were the keywords with the strongest citation bursts until 2021. Conclusions: This study provided a complete analysis of the research on TE. The effect of ADM on the complication rates after breast reconstruction is the current hotspot of TE research in surgery. Patient-activated controlled expansion might be a promising future research direction for TE.