Superficial circumflex iliac artery perforator propeller flap for penoscrotal extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare intra-epidermal adenocarcinoma, and reconstruction of the penoscrotal region remains a clinical challenge. The superficial circumflex iliac artery perforator (SCIP) flap has been successfully used as a free flap, while its application as a propeller flap in the reconstruction of penoscrotal EMPD defect is rarely reported. The objective was to evaluate the safety and efficacy of the SCIP propeller flap in the reconstruction of penoscrotal defects in EMPD. METHODS: Between September 2010 and August 2022, consecutive patients diagnosed with penoscrotal EMPD were enrolled. All patients underwent penoscrotal EMPD excision and reconstruction with SCIP propeller flap combined with other flaps or skin grafts on individual defects. Demographic information, surgical parameters, postoperative complications, patient satisfaction, and recurrence rates were analyzed. RESULTS: Twenty-four patients (mean age, 73 ± 8.8 years; mean BMI, 23.98 ± 3.62 kg/m2) with 33 SCIP propeller flaps (mean size 120.1 cm2; range, 24-208 cm2) were included, and the mean defect size was 67.4 cm2 (range, 12-255 cm2). The mean operative duration was 385.4 ± 146.8 min. Fifteen patients received autologous full-thickness skin grafts, and four received other flaps simultaneously. All flaps survived without total or partial loss, and all donor sites achieved primary closure, though local hematoma (one case) and limited skin graft necrosis (two cases) were observed. All patients experienced complete wound healing and maintained penoscrotal morphology and function without recurrent lesions over a mean follow-up of 59 months. CONCLUSIONS: The SCIP propeller flap seems a safe and effective reconstructive method for penoscrotal EMPD. LEVEL OF EVIDENCE: IV.

Distraction force promotes the osteogenic differentiation of Gli1+ cells in facial sutures via primary cilia-mediated Hedgehog signaling pathway.

BACKGROUND: Trans-sutural distraction osteogenesis (TSDO) involves the application of distraction force to facial sutures to stimulate osteogenesis. Gli1+ cells in the cranial sutures play an important role in bone growth. However, whether Gli1+ cells in facial sutures differentiate into bone under distraction force is unknown. METHODS: 4-week-old Gli1ER/Td and C57BL/6 mice were used to establish a TSDO model to explore osteogenesis of zygomaticomaxillary sutures. A Gli1+ cell lineage tracing model was used to observe the distribution of Gli1+ cells and explore the role of Gli1+ cells in facial bone remodeling. RESULTS: Distraction force promoted bone remodeling during TSDO. Fluorescence and two-photon scanning images revealed the distribution of Gli1+ cells. Under distraction force, Gli1-lineage cells proliferated significantly and co-localized with Runx2+ cells. Hedgehog signaling was upregulated in Gli1+ cells. Inhibition of Hedgehog signaling suppresses the proliferation and osteogenesis of Gli1+ cells induced by distraction force. Subsequently, the stem cell characteristics of Gli1+ cells were identified. Cell-stretching experiments verified that mechanical force promoted the osteogenic differentiation of Gli1+ cells through Hh signaling. Furthermore, immunofluorescence staining and RT-qPCR experiments demonstrated that the primary cilia in Gli1+ cells exhibit Hedgehog-independent mechanosensitivity, which was required for the osteogenic differentiation induced by mechanical force. CONCLUSIONS: Our study indicates that the primary cilia of Gli1+ cells sense mechanical stimuli, mediate Hedgehog signaling activation, and promote the osteogenic differentiation of Gli1+ cells in zygomaticomaxillary sutures.

SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2 Promoter.

Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells. IMPLICATIONS: Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.

Safety and Effectiveness of Laser or Intense Pulsed Light Treatment for Early Surgical Scar: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to investigate the safety and efficacy of laser or intense pulsed light therapy for early treatment of surgical scar. METHODS: A literature search was conducted for relevant prospective, randomized controlled trials published in PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang Database, and VTTMS between January 2006 and January 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used to extract literature data. The risk of bias was assessed by RevMan. Safety was assessed based on the presence of serious adverse reactions (blisters, infections, burns above the second degree), while effectiveness was assessed using the Vancouver Score Scale. RESULTS: 1512 related articles were preliminarily retrieved, including 1211 English articles and 301 Chinese articles. According to the inclusion criteria and exclusion criteria, 12 articles were selected for this analysis. In total, 475 patients were included (laser group, 238; control group, 236). All studies confirmed that the laser group was superior to the control group. In the subgroup analysis of 7 articles, the standardized mean difference was 1.99 (P = 0.0001). CONCLUSIONS: This meta-analysis demonstrates that laser or intense pulsed light therapy is a safe and effective approach for early surgical scar treatment, resulting in improved scar appearance and minimal adverse reactions. LEVEL OF EVIDENCE I: 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 .

Aesthetic Enhancement of the Gonial Angle and Inferior Mandibular Border in the Chinese Population.

BACKGROUND: The current absence of a standardized mandibular body osteotomy design poses challenges in surgical planning. Traditional approaches may not suit patients with wider anterior mandibles, potentially resulting in unsatisfactory outcomes. Addressing this issue requires a rational design that combines mandibular angle and body osteotomies for improved clinical practice. OBJECTIVES: In this retrospective cohort study we aimed to analyze mandibular computed tomography (CT) data with digital methods. The goal was to establish an integrated osteotomy design for both mandibular angle and body procedures and classify prevalent mandibular types in the Chinese Han population for surgical guidance. METHODS: Included were 89 patients who underwent mandibular angle osteotomy without genioplasty between 2016 and 2022 at Peking University Third Hospital. Mimics 21.0 software facilitated CT data reconstruction and osteotomy planning. Postoperative effects were assessed through imaging, complications, and surveys, leading to mandibular type classification. RESULTS: Mandibular angles were categorized by 3 types, based on osteotomy range. Type I involved mandibular body osteotomy only, type II mandibular angle osteotomy only, and type III both mandibular angle and body osteotomies. Distribution within the cohort was 2.25%, 8.99%, and 88.76% for types I, II, and III respectively. Patient satisfaction was high, with minor and major complications at 47.19% and 1.12% by Clavien-Dindo classification. CONCLUSIONS: Utilizing Mimics software, we established an integrated osteotomy design and categorized mandibular types. Findings offer valuable guidance for mandibular angle surgery and contribute to understanding of Asian mandibular morphology.

The SHH-GLI1 pathway is required in skin expansion and angiogenesis.

To investigate the role of GLI1 on skin proliferation and neovascularization during skin expansion in mice. We constructed GLI1-cre/R26-Tdtomato and GLI1-cre/R26-mtmg gene-tagged skin expansion mouse models. Using a two-photon in vivo imaging instrument to observe the changes in the number and distribution of GLI1(+) cells during the expansion process and to clarify the spatial relationship between GLI1(+) cells and blood vessels during the expansion process. In vitro proliferation assays were performed to further validate the effects of SHH (sonic hedgehog) and its downstream component GLI1 on cell proliferation viability. Finally, qRT-PCR was used to verify the changes in proliferation, angiogenesis-related factors, SHH signalling pathway-related factors, and the role of GLI1 cells in the process of skin expansion in mice. The number of GLI1(+) cells increased during dilation and were attached to the outer membrane of the vessel. The epidermis was thickened and the dermis thinned after the dilated skin was taken, while the epidermal thickening was suppressed and the dermis became thinner after the GLI1 cells were inhibited. The non-inhibited group showed a significant increase in PCNA positivity with prolonged dilation compared to the GANT61(GLI specificity inhibitor) inhibited group; CD31 immunofluorescence showed a significant increase in the number of dilated skin vessels and a significant decrease in the number of vessels after treatment with GANT61 inhibitor. In vitro proliferation results showed that SHH signalling activator significantly increased the proliferation viability of GLI1(+) hair follicle mesenchymal stem cells, while GNAT61 significantly inhibited the proliferation viability of GLI1(+) hair follicle mesenchymal stem cells. GLI1 is necessary for proliferation and neovascularization in expansion skin of mice through activation of the SHH signalling pathway.

Targeting the Glycolytic Enzyme PGK1 to Inhibit the Warburg Effect: A New Strategy for Keloid Therapy.

BACKGROUND: Aerobic glycolysis (the Warburg effect) may play an important role in keloid pathogenesis, which may be aggravated by the hypoxic microenvironment in keloids. Phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme, is essential for cellular aerobic glycolysis, but its role in keloid formation remains unknown. This study aimed to detect PGK1 expression in keloid tissue and investigate the effects of inhibiting PGK1 expression on keloid fibroblasts (KFbs) under hypoxia and normoxia. METHODS: Normal skin and keloid samples were separated into two parts, one was used for immunohistochemistry, and one for primary cell culture. PGK1 tissue expression was detected by immunohistochemistry. Reverse-transcriptase polymerase chain reaction and Western blotting were used to detect PGK1, GLUT1, LDHA, and COL1 expression, and glucose uptake and lactate production were detected with a microplate reader. Cell proliferation and apoptosis were investigated with IncuCyte and flow cytometry. Cell migration and invasion were detected with Transwell assays. Glycolytic function was explored with the Seahorse XF96 system. RESULTS: Immunohistochemistry showed PGK1 overexpression in keloid tissue compared with normal skin tissue ( P < 0.05). Consistently, PGK1 expression was significantly higher in KFbs than in normal skin fibroblasts (NFbs), and hypoxia stimulated PGK1 expression in KFbs and NFbs ( P < 0.05). PGK1 knockdown significantly inhibited KFb glycolysis, proliferation, migration, invasion, glucose consumption, and lactate production ( P < 0.05). Furthermore, GLUT1, LDHA, and COL1 expression was decreased in KFbs compared with NFbs ( P < 0.05). In addition, suppressing PGK1 may mediate the PI3K/AKT pathway to down-regulate GLUT1, LDHA, and COL1 expression ( P < 0.05). CONCLUSIONS: These findings provide new evidence that suppressing PGK1, inhibiting glycolysis, reduces KFb proliferation, migration, invasion, and type I collagen expression. Targeting PGK1 to inhibit the Warburg effect may be a new therapeutic strategy for keloids. CLINICAL RELEVANCE STATEMENT: This article may provide new suggestions into the pathogenesis and treatment of keloids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Regional flap: A reliable coverage for post-radiation ulcer.

Ulcer in radiation-damaged tissue is a dilemma with limited treatment strategies. The study aimed to evaluate the safety and efficacy of regional flaps for patients with post-radiation ulcers through a 10-year experience. A retrospective study of consecutive patients with post-radiation ulcers at a single institute from 2012 to 2022 was conducted. Reconstruction included complete excision of irradiated tissue and coverage with well-vascularised tissue, including local flaps, regional flaps and free flaps. Study outcomes included complications, reoperation rates, overall flap success and recurrence rates. Thirteen patients (six males and seven females; mean age, 56.85 ± 13.87 years) with a mean 10-month history of post-radiation ulcers were enrolled. Ulcers are predominantly located in the chest (n = 3, 23.1%), head (n = 2, 15.4%) and neck (n = 2, 15.4%), with a mean size of 33.1 cm2 (range from 1 cm2 to 120 cm2 ). Eleven patients underwent reconstruction with 15 regional flaps and three local flaps, one patient received a free anterolateral thigh fasciocutaneous flap and one patient underwent amputation. Among these 15 regional flaps, one (6.7%) had wound dehiscence and four (26.7%) had localised necrosis requiring reoperation. In addition, one patient with a non-healing sinus tract underwent reoperation. The overall success rate of the regional flap was 100% and no recurrence was observed with a mean follow-up of 23.3 months. Regional flaps seem a safe and effective reconstructive method for post-radiation ulcers.

PI3K/AKT pathway promotes keloid fibroblasts proliferation by enhancing glycolysis under hypoxia.

Our previous study demonstrated altered glucose metabolism and enhanced phosphorylation of the PI3K/AKT pathway in keloid fibroblasts (KFb) under hypoxic conditions. However, whether the PI3K/AKT pathway influences KFb cell function by regulating glucose metabolism under hypoxic conditions remains unclear. Here, we show that when PI3K/AKT pathway was inactivated with LY294002, the protein expression of glycolytic enzymes decreased, while the amount of mitochondria and mitochondrial membrane potential increased. The key parameters of extracellular acidification rate markedly diminished, and those of oxygen consumption rate significantly increased after inhibition of the PI3K/AKT pathway. When the PI3K/AKT pathway was suppressed, the levels of reactive oxygen species (ROS) and mitochondrial ROS (mitoROS) were significantly increased. Meanwhile, cell proliferation, migration and invasion were inhibited, and apoptosis was increased when the PI3K/AKT pathway was blocked. Additionally, cell proliferation was compromised when KFb were treated with both SC79 (an activator of the PI3K/AKT pathway) and 2-deoxy-d-glucose (an inhibitor of glycolysis), compared with the SC79 group. Moreover, a positive feedback mechanism was demonstrated between the PI3K/AKT pathway and hypoxia-inducible factor-1α (HIF-1α). Our data collectively demonstrated that the PI3K/AKT pathway promotes proliferation and inhibits apoptosis in KFb under hypoxia by regulating glycolysis, indicating that the PI3K/AKT signalling pathway could be a therapeutic target for keloids.

Application of depithelized gracilis adipofascial flap for pelvic floor reconstruction after pelvic exenteration.

BACKGROUND: Pelvic exenteration is a radical surgery performed in selected patients with locally advanced or recurrent pelvic malignancy. It involves radical en bloc resection of the adjacent anatomical structures affected by the tumor. The authors sought to evaluate the clinical application of a depithelized gracilis adipofascial flap for pelvic floor reconstruction after pelvic exenteration. METHODS: A total of 31 patients who underwent pelvic floor reconstruction with a gracilis adipofascial flap after pelvic exenterationat Peking University Third Hospital from 2014 to 2022 were enrolled in the study. The postoperative follow-up durations varied from 4 to 12 months. RESULTS: The survival rate of the flap was 96.77% with partial flap necrosis in one case. The total incidence of postoperative complications associated with the flap was 25.81%, with an incidence of 6.45% in the donor site and 19.35% in the recipient site. All complications were early complications, including postoperative infection and flap necrosis. All patients recovered after treatments, including anti-infectives, dressing change, debridement, and local flap repair. Long-term follow-up showed good outcomes without flap-related complications. CONCLUSIONS: A depithelized gracilis adipofascial flap can be applied for pelvic floor reconstruction after pelvic exenteration. The flap is an ideal and reliable choice for pelvic floor reconstruction with few complications, an elevated survival rate, sufficient volume, and mild effects on the function of the donor site.

Clinical study on orthopaedic treatment of chronic osteomyelitis with soft tissue defect in adults.

To investigate the clinical application value of different flap transfer and repair techniques in adult patients with chronic osteomyelitis of limbs complicated with soft tissue defects. According to the characteristics and defects of 21 cases, different plastic surgery was applied, including debridement, negative pressure device, and tissue flap to cover wound. Among 21 cases of chronic osteomyelitis complicated with local soft tissue defect, 15 patients were repaired with sural neurotrophic musculocutaneous flap transfer, 2 patients were repaired with medial plantar skin flap transfer, 2 patients were repaired with ilioinguinal skin flap transfer, 1 patient was repaired with z-forming wound, and 1 patient was repaired with soleus muscle flap combined with full-thickness skin graft. All the 21 patients underwent bone cement implantation after dead bone osteotomy. Among them, 19 patients underwent bone cement replacement with 3D prosthesis within 6 months to 1 year after surgery, and 2 patients carried bone cement for a long time. Early intervention, thorough debridement, removal of necrotic or infection, and then selecting the appropriate wound skin flap coverage are important means of guarantee slow osteomyelitis wound healing and for providing a possible way to permanent prosthesis implantation subsequently.

The application of local rotating flap and latissimus dorsi flap in thoracic deformity correction.

BACKGROUND: Wound healing problem is one of the main complications after correction of chest wall deformity. Orthopedic flap tissue repair technique has a clear significance in non-healing wound and defect wound and provides a new choice for poor wound healing after orthopedic surgery of chest wall deformity. OBJECTIVE: To investigate, the application value of modified local rotary flap and latissimus dorsi myocutcutaneous flap in the treatment of poor wound healing after orthodontic treatment of chest wall deformity. METHOD: A retrospective analysis was performed on patients who admitted to our department from August 2012 to November 2019 due to non-healing incision after surgery for thoracic deformity. Skin flap was selected according to the size of the wound surface, and the effect of skin flap repair was observed. The clinical data of the included patients were recorded, and the preoperative and postoperative wound conditions were evaluated. RESULTS: This study included 13 patients with chest wall deformity who received plastic surgery tissue using flap technique for wound repair, 11 cases used modified local rotation skin flap, and 2 cases used modified latissimus dorsi myocutaneous flap. The mean age of the 13 patients was 18.54 ± 4.14 years old, the mean body mass index (BMI) was 17.02 ± 2.16 kg/m2 , and the mean preoperative nonunion time of the incision was 64.77 ± 93.01 days. Five patients had positive bacteria culture on the wound surface, including 3 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa, and 1 case of Staphylococcus epidermidis. All the 13 patients achieved primary grade A healing. CONCLUSION: The modified local rotary flap and latissimus dorsi musculocutaneous flap have a significant effect on the postoperative correction of chest wall deformity, which can ensure wound healing while retaining the orthopedic plate to the maximum extent to ensure the effect of the correction.

Clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap.

We aimed to explore the clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap. Five patients who underwent pedicled axial flap transfer to repair a large area of skin and soft tissue defects in our hospital were included in this retrospective study. Detailed information including general data and clinical data, such as preoperative complication, type of primary wound, the distance between the primary wound and the donor site (cm), postoperative complications, and types of axial flap were collected. The patients had good joint movement at 6 months after pedicle amputation. At 48 hours after transplantation, except for the last patient (NO.5), there were no obvious complications such as blood supply disorder, infection, and incision dehiscence of the patients, and the flaps survived well. Just after pedicle amputation, 3 and 6 months after pedicle amputation, the flaps survived well with good local morphology. Forty-eight hours after operation, part of the distal flap in the last patient (NO.5) was necrotic. After 6 months of pedicle amputation, part of the flap was transferred to the distal wound again. At 6 months after pedicle amputation, these patients could accept local scars even though the scar of the last patient was obvious. The secondary pedicle amputation of the repair of distal defects with axial flap could avoid the compression of the vascular pedicle in the subcutaneous tunnel between the donor site and the primary wound, which may ensure the bold supply and increase the survival rate of the flap.

Suture Cells in a Mechanical Stretching Niche: Critical Contributors to Trans-sutural Distraction Osteogenesis.

Trans-sutural distraction osteogenesis has been proposed as an alternative technique of craniofacial remodelling surgery for craniosynostosis correction. Many studies have defined the contribution of a series of biological events to distraction osteogenesis, such as changes in gene expression, changes in suture cell behaviour and changes in suture collagen fibre characteristics. However, few studies have elucidated the systematic molecular and cellular mechanisms of trans-sutural distraction osteogenesis, and no study has highlighted the contribution of cell-cell or cell-matrix interactions with respect to the whole expansion process to date. Therefore, it is difficult to translate largely primary mechanistic insights into clinical applications and optimize the clinical outcome of trans-sutural distraction osteogenesis. In this review, we carefully summarize in detail the literature related to the effects of mechanical stretching on osteoblasts, endothelial cells, fibroblasts, immune cells (macrophages and T cells), mesenchymal stem cells and collagen fibres in sutures during the distraction osteogenesis process. We also briefly review the contribution of cell-cell or cell-matrix interactions to bone regeneration at the osteogenic suture front from a comprehensive viewpoint.

The Application of Cartilage Tissue Engineering with Cell-Laden Hydrogel in Plastic Surgery: A Systematic Review.

BACKGROUND: As a contour-supporting material, the cartilage has a significant application value in plastic surgery. Since the development of hydrogel scaffolds with sufficient biomechanical strength and high biocompatibility, cell-laden hydrogels have been widely studied for application in cartilage bioengineering. This systematic review summarizes the latest research on engineered cartilage constructed using cell-laden hydrogel scaffolds in plastic surgery. METHODS: A systematic review was performed by searching the PubMed and Web of Science databases using selected keywords and Medical Subject Headings search terms. RESULTS: Forty-two studies were identified based on the search criteria. After full-text screening for inclusion and exclusion criteria, 18 studies were included. Data collected from each study included culturing form, seed cell types and sources, concentration of cells and gels, scaffold materials and bio-printing structures, and biomechanical properties of cartilage constructs. These cell-laden hydrogel scaffolds were reported to show some feasibility of cartilage engineering, including better cell proliferation, enhanced deposition of glycosaminoglycans and collagen type II in the extracellular matrix, and better biomechanical properties close to the natural state. CONCLUSION: Cell-laden hydrogels have been widely used in cartilage bioengineering research. Through 3-dimensional (3D) printing, the cell-laden hydrogel can form a bionic contour structure. Extracellular matrix expression was observed in vivo and in vitro, and the elastic modulus was reported to be similar to that of natural cartilage. The future direction of cartilage tissue engineering in plastic surgery involves the use of novel hydrogel materials and more advanced 3D printing technology combined with biochemistry and biomechanical stimulation.

Chondrocyte Spheroids Laden in GelMA/HAMA Hybrid Hydrogel for Tissue-Engineered Cartilage with Enhanced Proliferation, Better Phenotype Maintenance, and Natural Morphological Structure.

Three-dimensional cell-laden tissue engineering has become an extensive research direction. This study aimed to evaluate whether chondrocyte spheroids (chondro-spheroids) prepared using the hanging-drop method could develop better cell proliferation and morphology maintenance characteristics, and be optimized as a micro unit for cartilage tissue engineering. Chondro-spheroids were loaded into a cross-linkable hybrid hydrogel of gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) in vivo and in vitro. Cell proliferation, aggregation, cell morphology maintenance as well as cartilage-related gene expression and matrix secretion in vitro and in vivo were evaluated. The results indicated that compared with chondrocyte-laden hydrogel, chondro-spheroid-laden hydrogel enhanced proliferation, had better phenotype maintenance, and a more natural morphological structure, which made it appropriate for use as a micro unit in cartilage tissue engineering.

Extracellular vesicles derived from lipoaspirate fluid promote fat graft survival.

Extracellular vesicles (EVs) are specific subcellular vesicles released by cells under various environmental conditions. Tumescent liposuction is a commonly used procedure in plastic surgery practice. In the present study, we aimed to extract EVs derived from lipoaspirate fluid (LF-EVs) and characterize them using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. The global profiles of proteins and microRNAs from LF-EVs were identified, strongly suggesting a potential regulatory function of LF-EVs. In addition, we investigated the effects and mechanisms of LF-EVs on fat graft survival. Cell functional tests showed that LF-EVs promoted the proliferation, migration, and tube structure formation of human umbilical vein endothelial cells. LF-EVs also promoted the adipogenic differentiation of adipose tissue-derived stem cells. The results of animal experiments showed that the average weights of fat grafts in the LF-EVs-treated group were significantly higher than those in the control group. Histologically, there was less fibrosis, fewer cysts, and increased fat tissue survival in the LF-EVs group. Further investigations of angiogenic and adipogenic factors revealed that LF-EVs also promoted angiogenesis and exerted a pro-adipogenic effect in vivo. Our findings will help to elucidate the functions of LF-EVs and provide a reference dataset for future translational studies.

Adipose-Derived Stem Cells Promote Bone Coupling in Bisphosphonate-Related Osteonecrosis of the Jaw by TGF-ß1.

This study aimed to investigate molecularly targeted therapy to revive bone remodeling and prevent BRONJ by local adipose-derived stem cells (ADSCs) transplantation. Clinical samples of BRONJ and healthy jawbones were used to examine the bone coupling-related cells and TGF-ß1 expression. Bone coupling-related cells and TGF-ß1 expression were also assessed in BRONJ-like animal model to confirm the results in clinical samples. ADSCs were locally administered in vivo and the therapeutic effects were evaluated by gross observation, radiological imaging, and histological examination. Furthermore, ADSCs-conditioned medium (ADSCs-CM) and neutralizing antibody were applied to assess the effects of ADSCs-derived TGF-ß1 on restoring bone coupling in vivo. Osteoclast formation and resorption assays were performed to evaluate the effects of ADSCs-derived TGF-ß1 on ZA-treated pre-osteoclasts. Cell migration was performed to assess the effects of ADSCs-derived TGF-ß1 on patients' bone marrow stem cells (BMSCs). The number of osteoclasts, Runx2-positive bone-lining cells (BLCs) and TGF-ß1 expression were decreased in BRONJ and animal model jaw bone samples. These reductions were significantly rescued and necrotic jawbone healing was effectively promoted by local ADSCs administration in BRONJ-like animal models. Mechanistically, ADSCs-CM mainly contributed to promoting bone coupling, while TGF-ß1 neutralizing antibody in the conditioned medium inhibited these effects. Besides, osteoclastogenesis and patients' BMSCs migration were also rescued by ADSCs-derived TGF-ß1. Furthermore, bone resorption-released bone matrix TGF-ß1, together with ADSCs-derived TGF-ß1, synergistically contributed to rescuing BMSCs migration. Collectively, ADSCs promoted bone healing of BRONJ by TGF-ß1-activated osteoclastogenesis and BMSCs migration capacities.

Combined Use of Autologous Stromal Vascular Fraction Cells and Platelet-Rich Plasma for Chronic Ulceration of the Diabetic Lower Limb Improves Wound Healing.

The discovery of stromal vascular fraction cells and platelet-rich plasma in promoting tissue regeneration has prompted a new idea for the treatment of chronic diabetic ulcer of the lower limb. The study aim was to evaluate the clinical efficacy of a new method that applied stromal vascular fraction cells and platelet-rich plasma together in the treatment of recalcitrant chronic diabetic ulcer. We conducted a single-center, prospective, open, noncontrolled study. Four patients (5 ulcers in total) who had received standard treatment for diabetic ulcer for at least 3 months that failed to heal was enrolled. All patients were treated with surgical debridement, cell suspension (stromal vascular fraction cells suspended by platelet-rich plasma) injection into the wound, and platelet-rich plasma gel coverage. Wounds were measured every week after treatment using a 2-dimensional digital camera and a 3-dimensional wound measurement device. All patients were followed-up for 4 months after the treatment. Four of the 5 ulcers healed completely within a mean of 71.75 ± 29.57 days. The average proportion of granulation tissue achieved 100% within 4 weeks for all cases. The wound size decreased to less than half of the original size for all cases 4 weeks after the treatment. Findings revealed that the new treatment is efficient to achieve wound healing in patients with recalcitrant chronic diabetic ulcer of lower limb.