Postoperative Morbidity Outcomes Associated With Superficial Temporal Versus Cervical Vessels as Recipient Vessels in Head and Neck Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: The purpose of this meta-analysis was to compare the surgical outcomes of head and neck reconstruction via free flap surgery, with neck vessels versus superficial temporal vessels as recipient vessels. METHODS: The PubMed, Embase, and Scopus databases were systematically searched via the following keywords: ("superficial temporal" OR "temporal") AND ("free flap" OR "free tissue transfer") AND ("head and neck" OR "face"). The following data were extracted: first author, publication year, flap type, reconstruction region, concordant vein graft, recipient vessel, and postoperative complications, including thrombosis, partial necrosis, and flap failure. The recipient vessels were divided into two groups: the superficial temporal artery (STA)/V group and the neck group. RESULTS: Six hundred and thirty-five studies that met the inclusion criteria were included and reviewed systematically for a meta-analysis. Compared with the neck vessel group, the STA/V vessel group had a significantly greater risk of flap failure (odds ratio: 2.18; 95% CI: 1.32-3.60; p = 0.002), with low heterogeneity (p = 0.84; I2 = 0%). However, there were no significant differences in the rates of thrombosis or partial necrosis. CONCLUSIONS: Compared with the use of neck vessels, the use of STA/V vessels as recipient vessels for head and neck reconstruction could increase the risk of total flap necrosis. Considering these findings, surgeons should exercise caution when selecting the STV as the recipient site, and as some authors have suggested, proximal dissection may be necessary during surgery.

Effect of Surgical Timing to Dental Health in Secondary Alveolar Bone Grafting: Three-Dimensional Outcomes.

BACKGROUND: There are various opinions on the optimal timing for performing secondary alveolar bone grafting (SABG). This study compared dental health and 3-dimensional outcomes according to the timing of SABG surgery. PATIENTS AND METHODS: A retrospective chart review was performed in patients who underwent SABG between January 1996 and October 2020. Patients were divided into early SABG (6-8 y old) and traditional SABG (9-13 y old) groups. The final dental survival of the lateral incisor and canine teeth, survival of the bone graft, and maxillary growth were analyzed using plain radiographs and computed tomography with a 3-dimensional volumetric analysis tool. RESULTS: Thirty-six patients were divided into an early group (15 patients) and a traditional group (21 patients). Five patients had bilateral cleft lip, and 26 patients had unilateral cleft lip and palate; therefore, 36 alveolar clefts were analyzed in this study. Lateral incisor survival was significantly greater in the early group than in the traditional group (60% vs. 23.5%; P<0.05). Compared with that in the traditional group, graft success in the early group was greater (80% vs. 57.1%; P<0.05). Three-dimensional volumetric analysis revealed superior bone graft efficiency in the early group compared with the traditional group (55.2 vs. 38.5%; P<0.05). There was no significant difference in maxillary growth between the 2 groups. CONCLUSIONS: In our study, superior dental and clinical outcomes were observed in the early SABG group without any long-term complications or maxillary retrusion. Our institution cautiously indicated that SABG could be performed at an age earlier than the existing SABG performed after 9 years old.

Long-Term Comparison of Esthetic Outcomes Between Hatchet and Transposition Flaps in Facial-Defect Reconstruction.

BACKGROUND: Transposition flaps are commonly used for facial-defect repair after wide excision of skin cancers. However, such repair often causes excessive tension at the donor site that can result in distortion of the adjacent area. The hatchet flap, a rotation-advancement flap, can prevent distortion by redistributing the donor site tension evenly to the recipient site. This study aims to compare the esthetic outcomes of the hatchet flap and transposition flap in facial-defect reconstruction. METHODS: We retrospectively included 50 patients who underwent facial reconstruction with the hatchet flap or transposition flap after excision of skin cancer. They were followed up for more than 6 months. At the last follow-up visit, the esthetic outcome was evaluated by subjective and objective assessments using the patients and observer scar assessment scale and Manchester scar scale. RESULTS: Thirty patients and 20 patients underwent reconstruction using the hatchet flap and the transposition flap, respectively. The total score from the patient and observer scar assessment scale was significantly lower in the hatchet flap group compared with the transposition flap group (p = 0.009). The Manchester scar scale showed a total score of 7.67 ± 2.2 for the hatchet flap and 9.95 ± 1.99 for the transposition flap: in the color (p < 0.001), distortion (p < 0.001), and texture (p < 0.02) categories, the hatchet flap yielded significantly better outcomes than the transposition flap. CONCLUSIONS: The hatchet flap had good esthetic outcome for facial reconstruction and could be a valuable option for reconstructing facial defects. 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 Table of Contents or online Instructions to Authors www.springer.com/00266.

Complete Preservation of Orbital Fat by Restoration of Attenuated Orbital Septa Using an Acellular Dermal Matrix in Lower Blepharoplasty.

BACKGROUND: We hypothesized that application of acellular dermal matrix (ADM) over the orbital septum overlying the herniated orbital fat to tighten and strengthen the attenuated orbital septum in lower blepharoplasty would allow successful repositioning of the herniated orbital fat within the bony orbit. METHODS: The author prospectively compared the cosmetic outcomes of lower blepharoplasty using ADM with standard blepharoplasty. We evaluated recurrence of eyelid bulging and tear trough deformity, volume of the lower periorbital region, and enophthalmos and eyelid droop 1 year after surgery. RESULTS: Twenty-two of the 24 enrolled patients completed the study. There was no significant difference in recurrence of eyelid bulging and tear trough deformity between standard blepharoplasty and blepharoplasty with ADM graft groups. In the standard blepharoplasty group, the volume of the lower periorbital region decreased significantly after surgery. In the blepharoplasty with ADM graft group, there was no significant change in the volume of the lower periorbital region after surgery. In the standard blepharoplasty group, there was no significant change in eyelid droop on either side after surgery. In the blepharoplasty with ADM graft group, the eyelid droop decreased significantly after surgery on the right side but showed no significant change on the left side. There was no significant change in enophthalmos after surgery for either group. CONCLUSIONS: This study demonstrated that ADM graft provided effective support for maintaining the replaced orbital fat in lower blepharoplasty. In the long-term, blepharoplasty with ADM graft might be effective in slowing development of age-related enophthalmos. 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 .

Comparative Study of En Bloc Excision and Dermal Shaving in Treating Axillary Osmidrosis.

BACKGROUND: Axillary osmidrosis is a distressing problem caused by hyperactivity of apocrine glands. There have been numerous studies on various surgical treatment methods. In this study, we evaluated the effectiveness of en bloc excision in comparison with dermal shaving. METHODS: The electronic records of 146 patients (286 axillae) who underwent surgery at our center for axillary osmidrosis between January 2009 and December 2020 were reviewed. Twenty-five patients (49 axillae) underwent en bloc excision and 121 (237 axillae) underwent dermal shaving. Patients in the en bloc excision group underwent Minor test preoperatively to detect sweating areas. Severity of osmidrosis was graded using a 4-point scale (0-3). A satisfaction questionnaire was used to evaluate patient experiences in the 2 types. RESULTS: Mean operation time was significantly shorter in the en bloc excision group than in dermal shaving group. Most en bloc excisions were performed on an outpatient basis under local anesthesia. Both groups showed an improvement in osmidrosis score at 6 months after surgery. A satisfaction questionnaire revealed better perioperative experiences in the en bloc excision group. Various surgical complications such as hematoma, wound dehiscence, and flap necrosis occurred in the dermal shaving group, and the en bloc excision group experienced significantly fewer complications that required intervention. CONCLUSIONS: En bloc excision combined with Minor test effectively reduces malodor without causing severe complications. In addition, perioperative patient satisfaction was better in the en bloc excision group than in the dermal shaving group as en bloc excision provided more rapid returns to normality and simplified communications with patients.

Harmonic scalpels compared with electrocautery in reconstructive flap harvesting: A meta-analysis.

BACKGROUND: Numerous studies have compared electrical devices used for flap surgery, but the results are inconsistent. This research was performed to evaluate the efficacy of two different types of electric devices: electrocautery and ultrasonic shears. METHODS: The PubMed, Embase, and Scopus databases were searched systematically. A total of 505 cases were included in this study, including 209 electrocautery and 296 harmonic scalpel cases. The following information was retrieved from the included studies: the first author of the article, publication year, flap type, flap harvest time, drain volume, bleeding volume and postoperative complications. Hematoma, infection, flap necrosis and wound dehiscence were considered postoperative complications. The Q statistic for heterogeneity and the I2 index were calculated. If I2 < 50%, we used a fixed-effects model; if I2 > 50%, we employed a random-effects model in our meta-analysis. RESULTS: A total of eight studies which met the inclusion criteria were included and reviewed systematically for a meta-analysis. The harmonic scalpel yielded a statistically significantly more favorable flap harvest time and drain volume than did electrocautery. The Harmonic scalpel led to a shorter flap harvest time by 26.29 min (95% CI = -39.38 to -13.2; p < .00001) and smaller drain volume by 58.76 ml (95% CI = -105.27 to -12.25; p = .01) on average. However, there were no significant differences in the bleeding volume or incidence rates of infection, flap necrosis and wound dehiscence. CONCLUSION: The Harmonic scalpel method yields better outcomes in terms of the flap harvest time and drain volume than does the conventional electrocautery method. Therefore, the Harmonic scalpel is a better option for cauterization and dissection in flap surgery.

A New Technique of Open Septal Reduction Using Polydioxanone Plates for Nasoseptal Fracture: Three-Dimensional Volumetric Analysis.

BACKGROUND: In this study, we designed a new technique for open septal reduction using a polydioxanone (PDS) plate and compared it with closed reduction (CR). METHODS: This study included 19 consecutive patients with nasoseptal fracture: 10 receiving open reduction with a PDS plate (PDS group) and 9 undergoing CR group. Open septal reduction was performed after CR for nasal bone fracture. A mucoperichondrial flap was unilaterally elevated, and the deviated septal cartilage was reduced. The PDS plate was inserted horizontally above the vomerine suture. Surgical outcome was analyzed with three-dimensional volumetry and with a quality-of-life scale for nasal obstruction (Nasal Obstruction Symptom Evaluation scale). RESULTS: Complications included 1 case of septal perforation in the CR group and 1 case of PDS exposure and septal hematoma in the PDS group. In the three-dimensional volumetric analysis of the PDS group, the median value of the nasal cavity change significantly differed between 1.14 mL (interquartile range; 0.46-2.4) at the preoperative computed tomography scan and 0.33 mL (interquartile range; -0.22 to 1.29) at the postoperative computed tomography scan (∗∗P = 0.0039). The Nasal Obstruction Symptom Evaluation scale revealed significant improvement in nasal obstruction postsurgically (median value, 42.5-7.5; ∗P = 0.0139) in the PDS group. CONCLUSIONS: Polydioxanone plates potentially present a new concept of open septal reduction in terms of septal reinforcement compared with the subtractive approach of open septal reduction.

Anthropometric Changes in the Upper Lip Between the Standing Position in the Clinic and Supine Position on the Operative Table in Secondary Cleft Lip Nasal Deformities.

BACKGROUND: We evaluated changes in lip height and length by position in cleft lip nasal deformity patients who underwent treatment with Millard technique. METHODS: A retrospective review of the medical records and an anthropometric analysis of photographs were performed in 209 cases of cleft lip nasal deformity. In the photogrammetric analysis, the lip height and length were calculated with respect to the intercanthal width. To evaluate the change in the difference between the cleft- and noncleft-side measurements between the standing and supine positions, the difference between the cleft- and noncleft-side measurements (Δnc-c) was calculated. We identified which patients and surgical factors affected the difference between the cleft- and noncleft-side measurements between the standing and supine positions (Δst-sp). RESULTS: From a total of 120 cases, cases with missing medical charts and clinical photographs were excluded, and 89 cases were included in this study. The discrepancy between the cleft-side lip height and noncleft-side lip height was significantly different between the standing and supine positions (P = 0.007). According to the univariate regression analysis, Δst-sp (sbal-cphi) had a significant positive correlation with body mass index (P = 0.044). In the final multiple linear regression analysis, body mass index had a significant positive correlation with Δst-sp (sbal-cphi, P = 0.044). CONCLUSION: In our results, the difference in vertical lip height is easy to underestimate in the supine position during surgery. Therefore, surgeons should verify lip height with the patient in the sitting or standing position during the operation to avoid undercorrecting lips with short heights.

The effect of combination therapy on critical-size bone defects using non-activated platelet-rich plasma and adipose-derived stem cells.

PURPOSE: Non-activated platelet-rich plasma (nPRP) slowly releases growth factors that induce bone regeneration. Adipose tissue-derived stem cells (ASCs) are also known to induce osteoblast differentiation. In this study, we investigated the combined effect of nPRP and ASC treatment compared with single therapy on bone regeneration. METHODS: Thirty New Zealand white rabbits with 15 × 15 mm2 calvarial defects were randomly divided into four treatment groups: control, nPRP, ASC, or nPRP + ASC groups. For treatment, rabbits received a collagen sponge (Gelfoam®) saturated with 1 ml normal saline (controls), 1 ml non-activated PRP (nPRP group), 2 × 106 ASCs (ASCs group), or 2 × 106 ASCs plus l ml nPRP (nPRP + ASCs group). After 16 weeks, bone volume and new bone surface area were measured, using three-dimensional computed tomography and digital photography. Bone regeneration was also histologically analyzed. RESULTS: Bone surface area in the nPRP group was significantly higher than both the control and ASC groups (p < 0.001 and p < 0.01, respectively). The percentage of regenerated bone surface area in the nPRP + ASC group was also significantly higher than the corresponding ratios in the control group (p < 0.001). The volume of new bone in the nPRP group was increased compared to the controls (p < 0.05). CONCLUSION: Our results demonstrate that slow-releasing growth factors from nPRP did not influence ASC activation in this model of bone healing. PRP activation is important for the success of combination therapy using nPRP and ASCs.

Septal Integration Graft, a Modified Direct Type of Septal Extension Graft for the Treatment of Unilateral Cleft Lip Nose Deformity: An Anthropometric Analysis.

BACKGROUND: The purpose of this study was to evaluate the cosmetic outcomes and stability of septal integration grafts (SIGs), a modified direct type of septal extension graft, in patients with cleft lip nose deformity. METHODS: Seventy-three patients underwent SIGs between January 2002 and July 2017. The exclusion criteria were patients who lacked clinical photographs preoperatively or postoperatively. We reviewed data regarding the patient demographics, combined procedures, and complications as well as preoperative and postoperative clinical photography. Eleven measurement items were evaluated from basal and right lateral views with photogrammetry and 3-dimensional anthropometry using standardized clinical photographic techniques. RESULTS: Sixty-one patients were analyzed in this study. Twelve patients were excluded owing to a lack of postoperative photographs. The mean ± SD follow-up period was 26.70 ± 29.43 months (range, 6-134 months). Compared with the preoperative value, the nasal tip projection index, height of nose index, and nostril axis inclination significantly improved. The columellar length (Rt-Lt) index significantly decreased, which implied improved columellar deviation. Complications included hematoma (n = 1), wound dehiscence (n = 1), tearing of septal mucosa (n = 3), and silicone implant deviation (n = 2). CONCLUSIONS: We used SIGs to correct nasal deformity in patients with cleft lip nose deformity. The SIG can minimize the amount of the graft used for septal extension and can effectively correct nasal tip and columella deformities.

Correlation between the inframammary fold and sixth rib: Application to breast reconstruction.

The inframammary fold (IMF) is an essential aesthetic element that influences the outcome of breast surgery. In this study, we introduced a new method for finding the IMF based on retrospective analysis of chest computed tomography (CT) scans of women's breasts. Sagittal sections of 80 female chest CTs were analyzed. Sagittal sections of 80 female chest CTs were analyzed by a single plastic surgeon. The distances between the fifth, sixth, and seventh ribs and the IMF were measured using Photoshop, and the location of the IMF was statistically analyzed according to age and height using paired t tests and Pearson's correlation test. As determined by our new method, the average distance between the IMF and the sixth rib was 5.33 mm, which was less than that between the IMF and any other rib. The IMF was closest to the sixth rib in all age groups (P < 0.001), and all IMFs were located between 39.5 mm superior and 24 mm inferior to the sixth rib. The sixth rib, one of the most visible reference structures in women's surface anatomy, is the "sentinel rib" for the IMF and the most predictive indicator of the location of the IMF. Knowing the original anatomic location of the IMF will enable better outcomes during breast surgery. Clin. Anat. 33:165-172, 2020. © 2019 Wiley Periodicals, Inc.

Subsegmental Osteotomy Technique With Distraction Osteogenesis for Natural Frontal Contouring in Metopic Synostosis.

Vectoring issues occur due to the dynamics of unidirectional procedure that is selected. To circumvent such difficulties, we have devised subsegmental osteotomy with distraction. In our technique, frontal bone flap was divided into 4 segments that were linked to each other by suturing wires in an 8-year-old patient with trigonocephaly. Subsegmental osteotomy and wiring of bone flap enabled us to slide bone in a more curvilinear manner and achieve natural contour. Distraction was initiated on postoperative day 7 at the rate of 1 mm/d for 20-mm gain. At the 9-year follow-up, the patient showed improved head shape and intellectual status.

Comparison of Pedal Soft Tissue Thickness Between Those With and Without Diabetes.

Ulceration is a serious consequence of diabetes that can lead to disability in patients with diabetes. One of the risk factors for ulceration is high foot pressure. The thickness of the pedal soft tissue is important because it has a cushioning effect. Soft tissue atrophy causes elevation in the plantar pressure, which, in turn, causes ischemia. Therefore, we investigated the severity of pedal soft tissue atrophy caused by diabetes and aging. From February 2009 to February 2016, we examined the feet of 261 patients treated in our hospital using magnetic resonance imaging. We divided the patients enrolled in the study into 2 groups. The first group included 52 patients with diabetes but without peripheral arterial disease and the second group included 47 patients without diabetes. We measured the vertical distances under all patients' metatarsal heads using T1-weighted magnetic resonance imaging and measured the pedal soft tissue thickness using the PACS workstation (m-view). We compared the soft tissue thicknesses of the 2 groups and performed statistical analyses of the relationships between these data and other parameters using 2-way analysis of variance. The soft tissue under the first to fourth metatarsal heads was thinner in the diabetic patients than in the nondiabetic patients (first metatarsal, 6.4 versus 8.69; second metatarsal, 8.85 versus 10.64; third metatarsal, 8.15 versus 9.21; fourth metatarsal, 7.38 versus 8.54; p < .05). Aging had no effect on pedal soft tissue atrophy in either group. In conclusion, our study confirmed that diabetic patients experience more severe plantar soft tissue atrophy than nondiabetic patients. We have developed a standard procedure to enable the prediction of pedal soft tissue atrophy severity in diabetic patients.

Scar Prevention and Enhanced Wound Healing Induced by Polydeoxyribonucleotide in a Rat Incisional Wound-Healing Model.

High-mobility group box protein-1 (HMGB-1) plays a central role in the inflammatory network, and uncontrolled chronic inflammation can lead to excessive scarring. The aim of this study was to evaluate the anti-inflammatory effects of polydeoxyribonucleotide (PDRN) on scar formation. Sprague-Dawley rats (n = 30) underwent dorsal excision of the skin, followed by skin repair. PDRN (8 mg/kg) was administered via intraperitoneal injection for three (PDRN-3 group, n = 8) or seven (PDRN-7 group, n = 8) days, and HMGB-1 was administered via intradermal injection in addition to PDRN treatment for three days (PDRN-3+HMGB-1 group; n = 6). The scar-reducing effects of PDRN were evaluated in the internal scar area and by inflammatory cell counts using histology and immunohistochemistry. Western blot, immunohistochemistry and immunofluorescence assays were performed to observe changes in type I and type III collagen and the expression of HMGB-1 and CD45. Treatment with PDRN significantly reduced the scar area, inflammatory cell infiltration and the number of CD45-positive cells. In addition, the increased expression of HMGB-1 observed in the sham group was significantly reduced after treatment with PDRN. Rats administered HMGB-1 in addition to PDRN exhibited scar areas with inflammatory cell infiltration similar to the sham group, and the collagen synthesis effects of PDRN were reversed. In summary, PDRN exerts anti-inflammatory and collagen synthesis effects via HMGB-1 suppression, preventing scar formation. Thus, we believe that the anti-inflammatory and collagen synthesis effects of PDRN resulted in faster wound healing and decreased scar formation.

Induction of delayed wound healing by irradiation with optional mechanical compression in swine.

A chronic wound or non-healing wound is one that fails to heal for at least 30 days after injury. This study was designed to create delayed wound healing induced by irradiation and mechanical compression using silicone block. Two female pigs received a single fraction of 20 Gy with 6-MeV electrons to a 22 × 60 cm field on the dorsal body skin 7 weeks before experimentation. A 30 × 30 mm sized wounds were created with preservation of muscle fascia on the dorsum. In groups of six, wounds were designated to be control (C) or test areas of irradiation only (T0), irradiation with silicone blocks for 1 week (T1), irradiation with silicone blocks for 2 weeks (T2), and irradiation with silicone blocks for 3 weeks (T3). Wound contraction, bacterial culture, and histological analysis were performed at 1-week intervals for 4 weeks. Control wounds displayed complete re-epithelialization at Weeks 4; however, all experimental groups (T0, T1, T2, and T3 groups) showed necrosis and delayed healing at Week 4. The number of bacterial strains in control wounds differed significantly from values recorded for all experimental groups from Weeks 1-3 (p < 0.05). However, in comparing the various test wounds (T0, T1, T2, and T3 groups), the numbers of strains did not differ significantly from Weeks 1-4. In the histological analysis, the control wound showed a peak influx of acute and chronic inflammatory cell and diminished inflammation thereafter. However, all experimental groups showed no peak in inflammatory score and prolonged chronic inflammation. In conclusion, radiation exposure alone, which triggers intense inflammation and extensive recruitment of inflammatory cells, proved sufficient to prevent re-epithelialization of skin at 30 days. Insertion of silicone blocks had limited effects on promoting delayed wound healing. Consequently, we now recommend using irradiation alone to simulate delayed wound healing in an experimental setting.

Risk of complications in panfacial bone fracture according to surgeons: A meta-analysis.

BACKGROUND: Panfacial bone fractures pose intricate challenges because of severe fragmentation and the loss of landmarks. Surgeons use a variety of reduction techniques, including bottom-up and top-down approaches. This single proportional meta-analysis explores sequencing differences and complications between oral and maxillofacial surgery surgeons (OMSs) and plastic and reconstructive surgeons (PRSs) in treating panfacial bone fractures. METHODS: The PubMed and Scopus databases were searched systematically, and we compiled 14 studies published between 2007 and 2023 involving 1238 patients. A systematic review of the included studies was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and data on the reduction techniques; total complication rates; and rates of malocclusion, enophthalmos, infection, asymmetry, and esthetic complications were collected. RESULTS: The bottom-up technique was the most prevalent for both types of surgeons (57.1%, 8 out of 14). Malocclusion rates (I2 = 0% for OMSs and 41% for PRSs) were similar between the groups (p = 0.72), but PRSs tended to have a lower enophthalmos rate (I2 = 0% for OMSs and 32% for PRSs) than OMSs (p < 0.01). Infection rates remained consistent across all studies. However, high heterogeneity was observed for the total complication rate (I2 = 94% for OMSs and 85% for PRSs) and asymmetry and esthetic complications (I2 = 88% for OMSs and 92% for PRSs), making direct comparison between the two groups inconclusive. CONCLUSIONS: In this study, the differences in surgical techniques and levels of interest have a greater impact on the outcomes of the panfacial bone fracture than the surgeon's specialty. However, more in-depth studies are needed to accurately pinpoint panfacial bone fracture reduction trends and differences in postoperative complications in the two expert groups.

Exploring the transcriptomic and metabolomic profiles of adipose tissues: Insights and implications for fat grafting.

BACKGROUND: Expanding on previous research on murine fat grafts' metabolic shift, this study delved deeper into the metabolic profiles of human adipose tissues, specifically the superficial subcutaneous adipose tissue (SSAT) and deep subcutaneous adipose tissue (DSAT). METHODS: Utilizing RNA sequencing, metabolomics, and metabolic flux analyses, SSAT and DSAT samples obtained during deep inferior epigastric perforator flap breast reconstructions were examined. Transcript data underwent unsupervised hierarchical clustering and Gene Set Enrichment Analysis. Metabolomics involved analyzing samples for cationic and anionic metabolites via capillary electrophoresis time-of-flight mass spectrometry, followed by principal component analysis (PCA) and heat map generation. Primary adipocytes from SSAT and DSAT were assessed using the Seahorse® extracellular flux analyzer. RESULTS: PCA and heat map analyses highlighted distinct transcriptomic and metabolomic differences between SSAT and DSAT. SSAT predominantly upregulated genes linked to adipogenesis [false discovery rate (FDR) q < 0.0001], oxidative phosphorylation (FDR q < 0.0001), fatty acid metabolism (FDR q < 0.0001), and glycolysis (FDR q = 0.001). In contrast, DSAT showed a significant upregulation in inflammatory response genes (FDR q < 0.05). Metabolite analysis revealed an abundance of glycolytic metabolites in SSAT, whereas DSAT was rich in metabolites associated with fatty acid metabolism and oxidative phosphorylation. Cellular flux analysis further confirmed SSAT's elevated glycolysis and spare oxidative phosphorylation capacities. CONCLUSION: Results highlighted the metabolic uniqueness of SSAT and DSAT in humans, with SSAT exhibiting superior metabolic flexibility. The implications of these metabolic differences, especially in fat grafting procedures, necessitate further research and exploration in future studies.

Unbiased transcriptome analysis of human cleft palate reveals evolutionally conserved molecular signatures of development: experimental study.

BACKGROUND: The development of the secondary palate, an essential process for hard palate formation, involves intricate cellular processes. Here, we examined the expression patterns of palatal fusion-associated genes in postdevelopmental human palatal tissues. METHODS: Mucosal samples collected from the anterior fused (control; n=5) and posterior unfused regions (study; n=5) of cleft palate patients were subjected to RNA sequencing. Gene Set Enrichment Analysis (GSEA) was conducted to identify consistent changes in molecular signaling pathways using hallmark (h) gene set collections from the Molecular Signature Database v7.4. The results of RNA sequencing were validated by epithelial-mesenchymal transition (EMT) assays with suppression of target genes, including lrp6, shh, Tgfß-3 (Bioneer, Daejeon, Korea), and negative control siRNA in a human fibroblast cell line (hs68). RESULTS: Transcriptome profiling of the cleft mucosa demonstrated that the fully fused anterior mucosa exhibited globally upregulated EMT, Wnt ß-catenin, Hedgehog, and TGF-ß signaling pathways in gene set enrichment. This strongly indicates the evolutionary conserved similarities in pathways implicated in palatogenesis, as previously shown in murine models. In EMT assays with suppression of Lrp6, Shh, and TGF-ß3 in human fibroblast cell lines, suppression of Lrp6 exhibited consistent suppression effects on EMT markers. This indicates a closer association with EMT compared to the other two signals. CONCLUSION: Our study highlights evolutionarily conserved molecular signatures and provides insights into the importance of the EMT pathway in palatal fusion in humans. Furthermore, intraindividual comparative analysis showed the spatial regulation of gene expression within the same organism. Further research and animal models are needed to explore the complexities of EMT-related palatal fusion.

Adipose-derived exosomes as a preventative strategy against complications in hyaluronic acid filler applications: A comprehensive in vivo analysis.

BACKGROUND: The aim of this study was to investigate the impact of exosomes derived from adipose-derived stem cells (ASCs) on complications arising from hyaluronic acid (HA) filler injections. METHODS: An HA hydrogel blended with adipose stem cell-derived exosomes was prepared and administered to the inguinal fat pads of 16 C57BL/6J mice. The control group received only HA filler (HA group), and the study group was treated with a combination of HA filler and exosomes (exoHA group). Biopsy was performed 1 week and 1, 2, 3, and 6 months after the injections. The effects were assessed using hematoxylin and eosin and Masson's trichrome staining for histological examination, immunohistochemistry for collagen type I and Vascular Endothelial Growth Factor (VEGF), RNA sequencing, and quantitative real-time polymerase chain reaction (PCR) (Il6, Ifng, Hif1a, Acta2, Col1a1). RESULTS: RNA sequencing revealed significant downregulation of the hypoxia (false discovery rate [FDR] q = 0.007), inflammatory response (FDR q = 0.009), TNFα signaling via NFκB (FDR q = 0.007), and IL6 JAK-STAT signaling (FDR q = 0.009) gene sets in the exoHA group. Quantitative PCR demonstrated a decrease in expression of proinflammatory cytokines (Il6, P < 0.05; Hif1a, P < 0.05) and fibrosis markers (Acta2, P < 0.05; Col1a1, P < 0.05) within the exoHA group, indicating reduced inflammation and fibrosis. Compared to the exoHA group, the HA group exhibited a thicker and more irregular capsules surrounding the HA filler after 6 months. CONCLUSION: The addition of ASC-derived exosomes to HA fillers significantly reduces inflammation and accelerates collagen capsule maturation, indicating a promising strategy to mitigate the formation of HA filler-related nodules.

Fat graft survival requires metabolic reprogramming toward the glycolytic pathway.

BACKGROUND: Fat grafts are widely used as natural fillers in reconstructive and cosmetic surgery. However, the mechanisms underlying fat graft survival are poorly understood. Here, we performed an unbiased transcriptomic analysis in a mouse fat graft model to determine the molecular mechanism underlying free fat graft survival. METHODS: We conducted RNA-sequencing (RNA-seq) analysis in a mouse free subcutaneous fat graft model on days 3 and 7 following grafting (n = 5). High-throughput sequencing was performed on paired-end reads using NovaSeq6000. The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heatmap generation, and gene set enrichment analysis. RESULTS: PCA and heatmap data revealed global differences in the transcriptomes of the fat graft model and the non-grafted control. The top meaningful upregulated gene sets in the fat graft model were related to the epithelial-mesenchymal transition, hypoxia on day 3, and angiogenesis on day 7. Mechanistically, the glycolytic pathway was upregulated in the fat graft model at days 3 (FDR q = 0.012) and 7 (FDR q = 0.084). In subsequent experiments, pharmacological inhibition of the glycolytic pathway in mouse fat grafts with 2-deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n = 5). CONCLUSIONS: Free adipose tissue grafts undergo metabolic reprogramming toward the glycolytic pathway. Future studies should examine whether targeting this pathway can enhance the graft survival rate.