Isolation of the Stromal Vascular Fraction Using a New Protocol with All Clinical-Grade Drugs: From Basic Study to Clinical Application.

OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Bioengineering autologous cartilage grafts for functional posterior lamellar eyelid reconstruction: A preliminary study in rabbits.

The reconstruction of posterior lamellar eyelid defects remains a significant challenge in clinical practice due to anatomical complexity, specialized function, and aesthetic concerns. The ideal substitute for the posterior lamellar should replicate the native tarsoconjunctival tissue, providing both mechanical support for the eyelids and a smooth surface for the globe after implantation. In this study, we present an innovative approach utilizing tissue-engineered cartilage (TEC) grafts generated from rabbit auricular chondrocytes and a commercialized type I collagen sponge to reconstruct critical-sized posterior lamellar defects in rabbits. The TEC grafts demonstrated remarkable mechanical strength and maintained a stable cartilaginous phenotype both in vitro and at 6 months post-implantation in immunodeficient mice. When employed as autografts to reconstruct tarsal plate defects in rabbits' upper eyelids, these TEC grafts successfully restored normal eyelid morphology, facilitated smooth eyelid movement, and preserved the histological structure of the conjunctival epithelium. When applied in bilayered tarsoconjunctival defect reconstruction, these TEC grafts not only maintained the normal contour of the upper eyelid but also supported conjunctival epithelial cell migration and growth from the defect margin towards the centre. These findings highlight that auricular chondrocyte-based TEC grafts hold great promise as potential candidates for clinical posterior lamellar reconstruction. STATEMENT OF SIGNIFICANCE: The complex structure and function of the posterior lamellar eyelid continue to be significant challenges for clinical reconstructive surgeries. In this study, we utilized autologous auricular chondrocyte-based TEC grafts for posterior lamellar eyelid reconstruction in a preclinical rabbit model. The TEC grafts exhibited native cartilaginous histomorphology and comparable mechanical strength to those of the native human tarsal plate. In rabbit models with either tarsal plate defects alone or bilayered tarsoconjunctival defects, TEC grafts successfully restored the normal eyelid contour and movement, as well as supported preservation and growth of conjunctival epithelium. This is the first study to demonstrate autologous TEC grafts can be employed for repairing tarsal plate defects, thereby offering an alternative therapeutic approach for treating posterior lamellar defects in clinic settings.

Exploration of treatment in childhood Langerhans cell histiocytosis based on inflammatory and malignant symptoms: a pilot study.

BACKGROUND: Multisystem childhood Langerhans cell histiocytosis (LCH) patients, especially those with risk organ (RO) involved, had not been satisfactorily treated under the international traditional schemes as high incidences of reactivation with late sequelae were largely reported. Over years, we have observed that LCH patients with varied clinical symptoms responded differently to different drugs, suggesting the current grouping strategies based only on the number of organs involved might be inadequate. LCH has been defined as an inflammatory myeloid tumor, thus this study has innovatively divided LCH pediatric patients into inflammatory or malignant symptoms group, and given different intensity treatment regimens to different groups. AIM: This clinical study aimed to explore a more appropriate patient grouping system according to the LCH symptom presentations and examine the clinical outcomes of treatment strategies in different groups. METHODS: According to the clinical manifestations, 37 cases of children were divided into Group A (only inflammatory symptoms) and Group B (malignant symptoms with or without inflammatory symptoms). Patients in Group A and B were initially treated with vindesine (VDS) and methylprednisolone (PSL), and VDS, PSL, pirarubicin (THP) and cyclophosphamide (CTX), respectively. Treatment responses were evaluated six weeks after the induction therapy in all patients, and the criteria were disease status and clinical scores of symptoms. RESULTS: Pre- and post-treatment scores were 1.22 ± 0.547 and 0.00 ± 0.00 in Group A, and 14.79 ± 1.686 and 1.00 ± 1.563 in Group B, respectively. All patients had subsequentlly received maintenance therapy without progressive disease. The 4-year overall survival (OS) rate was 100% in both groups and the 4-year event-free survival (EFS) was 94.4% in Group A and 89.5% in Group B, respectively. There were no obvious adverse events (AE) in Group A, whereas the main AE in Group B were alopecia and non-lethal hematological toxicity. CONCLUSION: Stratification according to patients' clinical symptoms, with low-intensity treatment for inflammatory symptoms (mild manifestations) and intensive treatment with multiple drugs for malignant symptoms (severe manifestations), is a positive exploration that simplifies stratification method, achieves good long-term remission of the disease, and obtains a higher survival rate and quality of life, which seemed to be more appropriate for LCH patients.

Bioengineering and vascularization strategies for islet organoids: advancing toward diabetes therapy.

Diabetes presents a pressing healthcare crisis, necessitating innovative solutions. Organoid technologies have rapidly advanced, leading to the emergence of bioengineering islet organoids as an unlimited source of insulin-producing cells for treating insulin-dependent diabetes. This advancement surpasses the need for cadaveric islet transplantation. However, clinical translation of this approach faces two major limitations: immature endocrine function and the absence of a perfusable vasculature compared to primary human islets. In this review, we summarize the latest developments in bioengineering functional islet organoids in vitro and promoting vascularization of organoid grafts before and after transplantation. We highlight the crucial roles of the vasculature in ensuring long-term survival, maturation, and functionality of islet organoids. Additionally, we discuss key considerations that must be addressed before clinical translation of islet organoid-based therapy, including functional immaturity, undesired heterogeneity, and potential tumorigenic risks.

Bioengineered human tissue regeneration and repair using endogenous stem cells.

We describe a general approach to produce bone and cartilaginous structures utilizing the self-regenerative capacity of the intercostal rib space to treat a deformed metacarpophalangeal joint and microtia. Anatomically precise 3D molds were positioned on the perichondro-periosteal or perichondral flap of the intercostal rib without any other exogenous elements. We find anatomically precise metacarpal head and auricle constructs within the implanted molds after 6 months. The regenerated metacarpal head was used successfully to surgically repair the deformed metacarpophalangeal joint. Auricle reconstructive surgery in five unilateral microtia patients yielded good aesthetic and functional results. Long-term follow-up revealed the auricle constructs were safe and stable. Single-cell RNA sequencing analysis reveal early infiltration of a cell population consistent with mesenchymal stem cells, followed by IL-8-stimulated differentiation into chondrocytes. Our results demonstrate the repair and regeneration of tissues using only endogenous factors and a viable treatment strategy for bone and tissue structural defects.

Body fluid-derived stem cells - an untapped stem cell source in genitourinary regeneration.

Somatic stem cells have been obtained from solid organs and tissues, including the bone marrow, placenta, corneal stroma, periosteum, adipose tissue, dental pulp and skeletal muscle. These solid tissue-derived stem cells are often used for tissue repair, disease modelling and new drug development. In the past two decades, stem cells have also been identified in various body fluids, including urine, peripheral blood, umbilical cord blood, amniotic fluid, synovial fluid, breastmilk and menstrual blood. These body fluid-derived stem cells (BFSCs) have stemness properties comparable to those of other adult stem cells and, similarly to tissue-derived stem cells, show cell surface markers, multi-differentiation potential and immunomodulatory effects. However, BFSCs are more easily accessible through non-invasive or minimally invasive approaches than solid tissue-derived stem cells and can be isolated without enzymatic tissue digestion. Additionally, BFSCs have shown good versatility in repairing genitourinary abnormalities in preclinical models through direct differentiation or paracrine mechanisms such as pro-angiogenic, anti-apoptotic, antifibrotic, anti-oxidant and anti-inflammatory effects. However, optimization of protocols is needed to improve the efficacy and safety of BFSC therapy before therapeutic translation.

Botulinum Toxin Type A Injection for Correction of Upper Eyelid Retraction in Thyroid-Associated Ophthalmopathy.

Upper lid retraction (ULR) is the most common and earliest symptom in thyroid-associated ophthalmopathy (TAO) patients. Surgical correction is effective for ULR in stable diseases. However, non-invasive treatment is also required for the TAO patient in active phase. Here, we reported a complex case with TAO and unilateral ULR simultaneously. The patient had a history of progressive ptosis in the left eyelid and underwent anterior levator aponeurotic-Muller muscle resection to correct the ptosis. However, the patient gradually developed bilateral proptosis and ULR, mainly in the left eyelid. The patient was finally diagnosed with TAO with left ULR. Then, the patient was treated with botulinum toxin type A (BTX-A) injection in the left eyelid. The effect of BTX-A treatment started 7 days after injection, peaked at one month, and lasted for approximately 3 months. This study highlighted the therapeutic effect of BTX-A injection for the treatment of ULR-related TAO.

Engineered M13 phage as a novel therapeutic bionanomaterial for clinical applications: From tissue regeneration to cancer therapy.

Bacteriophages (phages) are nanostructured viruses with highly selective antibacterial properties that have gained attention beyond eliminating bacteria. Specifically, M13 phages are filamentous phages that have recently been studied in various aspects of nanomedicine due to their biological advantages and more compliant engineering capabilities over other phages. Having nanofiber-like morphology, M13 phages can reach varied target sites and self-assemble into multidimensional scaffolds in a relatively safe and stable way. In addition, genetic modification of the coat proteins enables specific display of peptides and antibodies on the phages, allowing for precise and individualized medicine. M13 phages have also been subjected to novel engineering approaches, including phage-based bionanomaterial engineering and phage-directed nanomaterial combinations that enhance the bionanomaterial properties of M13 phages. In view of these features, researchers have been able to utilize M13 phages for therapeutic applications such as drug delivery, biodetection, tissue regeneration, and targeted cancer therapy. In particular, M13 phages have been utilized as a novel bionanomaterial for precisely mimicking natural tissue environment in order to overcome the shortage in tissue and organ donors. Hence, in this review, we address the recent studies and advances of using M13 phages in the field of nanomedicine as therapeutic agents based upon their characteristics as novel bionanomaterial with biomolecules displayed. This paper also emphasizes the novel engineering approach that enhances M13 phage's bionanomaterial capabilities. Current limitations and future approaches are also discussed to provide insight in further progress for M13 phage-based clinical applications.

Autologous Concentrated Growth Factor Increases Skin Thickness and Area during Tissue Expansion: A Randomized Clinical Trial.

BACKGROUND: Mechanical stretching of the skin (ie, tissue expansion) could generate additional skin, but it is limited by the intrinsic growth capacity. The authors conducted a study of autologous concentrated growth factor (CGF) to promote skin regeneration by increasing skin thickness and area during tissue expansion. METHODS: A single-center randomized controlled trial was conducted from 2016 to 2019. Participants undergoing skin expansion received either CGF or saline by means of intradermal injection on the expanded skin (0.02 mL/cm 2 ), for a total of three treatments at 4-week intervals. The primary endpoint was the expanded skin thickness at 12 weeks, which was measured by ultrasound. The secondary endpoints included skin thickness at 4 and 8 weeks and surface area, expansion index, and skin texture score of the expanded skin at 12 weeks. Safety assessments, for infection symptoms and nodule formation, were assessed at 24 weeks. RESULTS: In total, 26 patients were enrolled and assigned to the CGF or control group. Compared with the control group, the CGF group had significantly increased skin thickness at 8 (control, 1.1 ± 0.1 mm; CGF, 1.4 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047) and 12 weeks (control, 1.0 ± 0.1 mm; CGF, 1.3 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047). Compared with the baseline thickness (control, 1.6 ± 0.1 mm; CGF, 1.5 ± 0.1 mm; -0.3 to 0.5 mm; P = 0.987), skin thickness was sustained in the CGF group at 8 weeks after treatment (-0.1 to 0.3 mm; P = 0.711) but decreased in the control group (0.3 to 0.7 mm; P < 0.001). At 12 weeks, the CGF group showed greater increases in surface area (control, 77.7 ± 18.5 cm 2 ; CGF, 135.0 ± 15.7 cm 2 ; 7.2 cm 2 to 107.4 cm 2 ; P = 0.027) and expansion index (control, 0.9 ± 0.1; CGF, 1.4 ± 0.2; 0.0 to 0.8; P = 0.030) than the control group. In addition, CGF-treated skin showed an improvement in texture [CGF: grade 3, n = 2 (15.8%), grade 2, n = 4 (30.7%); control: grade 3, n = 0 (0.0%), grade 2, n = 3 (23.0%)]. No severe adverse events occurred. CONCLUSION: CGF treatment increases skin thickness and area during tissue expansion, and represents a safe and effective strategy for managing skin expansion. CLINICAL RELEVANCE STATEMENT: The findings of this study indicate that it is practically feasible to improve skin regeneration by applying autologous platelet concentrate therapy for skin expansion management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Downregulation of PLK4 expression induces apoptosis and G0/G1-phase cell cycle arrest in keloid fibroblasts.

OBJECTIVES: Keloids are benign fibroproliferative tumors that display many cancer-like characteristics, such as progressive uncontrolled growth, lack of spontaneous regression, and extremely high rates of recurrence. Polo-like kinase 4 (PLK4) was recently identified as a master regulator of centriole replication, and its aberrant expression is closely associated with tumorigenesis. This study aimed to investigate the expression and biological role of PLK4 in the pathogenesis of keloids. MATERIALS AND METHODS: We evaluated the expression of PLK4 in keloids and adjacent normal skin tissue samples. Then, we established PLK4 knockdown and overexpression cell lines in keloid fibroblasts (KFs) and normal skin fibroblasts (NFs), respectively, to investigate the roles of PLK4 in the regulation of proliferation, migration, invasion, apoptosis, and cell cycle in KFs. Centrinone B (Cen-B), a highly selective PLK4 inhibitor, was used to inhibit PLK4 activity in KFs to evaluate the therapeutic effect on KFs. RESULTS: We discovered that PLK4 was overexpressed in keloid dermal samples and KFs compared with adjacent normal skin samples and NFs derived from the same patients. High PLK4 expression was positively associated with the proliferation, migration, and invasion of KFs. Furthermore, knockdown of PLK4 expression or inhibition of PLK4 activity by Cen-B suppressed KF growth, induced KF apoptosis via the caspase-9/3 pathway, and induced cell cycle arrest at the G0/G1 phase in vitro. CONCLUSIONS: These findings demonstrate that PLK4 is a critical regulator of KF proliferation, migration, and invasion, and thus, Cen-B is a promising candidate drug for keloid treatment.

Autologous fat transfer rescues expanded skin from expansion failure: A retrospective cohort study in Asians.

BACKGROUND: Soft tissue expansion is a common technique for the regeneration of extra skin to repair skin defects. However, some warning signs like skin thinning and telangiectasia are often found during the expansion process, which indicates the skin flaps cannot be further expanded. These signs may result in the suspension of expansion or ultimately jeopardize the final outcome. Fat grafting is used to treat these potential complications and enable the continuation of the expansion procedure in some cases. In this study, we aimed to investigate the efficiency and safety of fat grafting in this process. METHODS: The study was conducted on patients from January 2012 to December 2017 with warning signs of expansion treated with fat grafting (treatment group) or pause expansion (control group). Follow-up data, such as expansion status, dermal thickness, telangiectasia, skin texture using volume assessment, B-mode ultrasound, and semiquantitative scoring, were collected. RESULTS: A total of 67 expanded skin regions with warning signs were enrolled. The expansion fold increased 2.14-fold at 12 weeks after treatment compared with 0.74-fold in control (P=0.02). The semiquantitative score was significant improved at 4 weeks (9.03 ± 0.73 vs. 7.45 ± 0.55; p=0.033). Meanwhile, the skin thickness in the experimental group did not show decreasing trend even in the continued expansion process. CONCLUSIONS: Autologous fat grafting represents an effective and safe method to rescue expanded skin from limited skin regeneration. This technique also represents a valuable tool to increase the chances for further expansion.

Long-Term Complications from Diced Cartilage in Rhinoplasty: A Meta-Analysis.

Objective: To analyze the incidences of long-term complications and revision surgery associated with diced cartilage grafts in dorsal augmentation rhinoplasty. Methods: The PubMed, MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for clinical studies on the use of diced cartilage for dorsal augmentation published. A meta-analysis was conducted to pool the estimated rates of infection, overcorrection, visible irregularity, absorption, and revision surgery. Result: A total of 14 studies involving 2380 patients were included in the systematic review. The combined rates were 11.5% for overall complications and 5.3% for revision surgery. The rates of the most frequently reported complications were 4.5% for infection, 5.3% for visible irregularity, 0.7% for overcorrection, and 0.5% for absorption. There was no significant difference in the rates of visible irregularity (p = 0.23) and revision surgery (p = 0.71) among the wrapped diced cartilage, glued diced cartilage, and free diced cartilage groups. Conclusion: This meta-analysis presents the first comprehensive and quantitative report of long-term complications associated with diced cartilage in dorsal augmentation rhinoplasty. Infection and visible irregularity were the most frequently reported complications. The rates of irregularity and revision surgery were not correlated with the diced cartilage packing methods.

A randomized, controlled clinical trial of autologous stromal vascular fraction cells transplantation to promote mechanical stretch-induced skin regeneration.

BACKGROUND: The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration. METHODS: This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks. RESULTS: The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI - 1.43 to - 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI - 1.30 to - 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI - 0.80 to - 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI - 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI - 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI - 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred. CONCLUSIONS: Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020-retrospectively registered).

Tranexamic Acid in Craniomaxillofacial Surgery: A Meta-Analysis and Systematic Review.

Objective: To compare the effectiveness of tranexamic acid (TXA) in reducing blood loss and decreasing surgery duration in craniomaxillofacial surgery. Methods: The literature was searched systematically for all comparative studies of the effect of TXA on craniomaxillofacial surgery with placebo to evaluate the efficacy of TXA in craniomaxillofacial surgery. The primary outcome was intraoperative blood loss, and secondary outcomes were postoperative hematocrit, postoperative hemoglobin, and operation duration. Results: This systematic review included 16 studies consisting of 958 patients. Meta-analysis revealed that compared with the placebo group, the TXA group showed a significant reduction in intraoperative blood loss of 139.81 mL (95% confidence interval, CI: -179.66 to -99.96 mL; p < 0.01), a shortening of the maxillary surgery duration of 15.48 min (95% CI: -21.03 to -9.92 min; p < 0.01), an elevation of the postoperative hemoglobin level of 0.74 mg/dL (95% CI: 0.42 to 1.07 mg/dL; p < 0.01), and a limited effect on increasing the postoperative hematocrit level of 1.77% (95% CI: 0.17 to 3.36; p = 0.03). Conclusion: The use of TXA in craniomaxillofacial surgery can effectively reduce intraoperative blood loss, maintain elevate postoperative hemoglobin and hematocrit levels, and reduce the operation duration.

A Four-Step Technique for Creating Individual Double-Eyelid Crease Shapes: A Free-Style Design.

BACKGROUND: Double-eyelid blepharoplasty is the most frequently performed aesthetic surgery in the Asian population. However, the epicanthal fold has been a conundrum limiting the outcomes of Asian blepharoplasty. Furthermore, with the blending of Western and Asian cultures, patients have individual standards of beauty for the upper eyelids. Here, we developed a four-step technique to form infold or outfold double-eyelid creases to satisfy individual patient requirements. METHODS: The medical records of patients who simultaneously underwent double-eyelid blepharoplasty and epicanthoplasty using this four-step technique from January of 2017 to January of 2019 were reviewed. The results were grouped by preoperative patient requirements for eyelid crease shapes. The rate of meeting patient expectations in each group was evaluated by two independent observers. Preoperative and postoperative photographs were collected, complications were identified, and postoperative results were assessed. RESULTS: In total, 285 consecutive patients were included in this study, with a mean follow-up period of 9 months. Of the 285 patients, 207 requested infold eyelid creases, and 190 (92 percent) procedures met patient expectations; and 78 patients requested outfold eyelid creases, and 69 (87 percent) procedures met patient expectations. A high rate of satisfaction with the final eyelid crease shape and resulting scarring was noted in both patient groups. The revision rate was 3 percent. No severe complications were observed. CONCLUSION: The four-step technique is a simple, flexible, and effective method for creating infold or outfold double-eyelid creases according to individual patient requirements and should be considered a routine method for patients who request double eyelids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Fat Grafting for Facial Contouring (Temporal Region and Midface).

In this article the authors introduce a compartment-based fat graft for facial contouring, focusing on the anatomy of temporal region and midface, the 3L3M integrated fat transfer technique, and the facial compartment-based fat injection in the face. This article includes details of pre-evaluation methods, results of cases, and postoperation care. Readers will have a clear view of how to do facial contouring fat graft in the face after reading this article. There seldom are complications while using the 3L3M technique for fat grafting. The targeted fat grafting can lead to steady and efficient results.

Early Postoperative Application of Botulinum Toxin Type A Prevents Hypertrophic Scarring after Epicanthoplasty: A Split-Face, Double-Blind, Randomized Trial.

BACKGROUND: Postoperative hypertrophic scarring of the medial canthal area is a common phenomenon and deterrent for patients considering epicanthoplasty. Botulinum toxin type A has been reported for hypertrophic scar and keloid treatment. However, there is a lack of high-level evidence regarding the effects of botulinum toxin type A in the medial canthal area. METHODS: In this split-face, double-blind, randomized trial, 43 consecutive consenting patients undergoing Park Z-epicanthoplasty were randomized to receive 5 U of botulinum toxin type A or the same volume of saline injections at days 6 to 7 postoperatively. Scars were assessed independently using the Vancouver Scar Scale, the visual analogue scale, and patient satisfaction rating at the 1-, 3-, and 6-month follow-ups. RESULTS: Overall, 30 patients completed this trial. The botulinum toxin type A-treated side achieved significantly improved Vancouver Scar Scale scores. The most obvious improvements were observed at the 3-month follow-up visit. Among the four subscores of the Vancouver Scar Scale, the most significantly improved subscores were the height and pliability. The visual analogue scale scores also decreased significantly on the botulinum toxin type A-treated side at all three follow-up visits. Approximately 86.7 percent of the patients were satisfied with the scar and epicanthoplasty outcomes. No severe complications were reported. CONCLUSIONS: Early postoperative botulinum toxin type A injection in the medial canthal region efficiently reduces hypertrophic scarring and improves the outcome of epicanthoplasty. Therefore, botulinum toxin type A injection can be used as a routine method to prevent hypertrophic scarring and improve the outcome of epicanthoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Long-term Outcomes of Temporal Hollowing Augmentation by Targeted Volume Restoration of Fat Compartments in Chinese Adults.

IMPORTANCE: Previous anatomical and clinical studies have suggested that targeted restoration of the volume and distribution of fat compartments using appropriate cannula entry sites and injection planes is an excellent fat-grafting technique for facial contouring and hand rejuvenation. OBJECTIVE: To perform subjective and objective evaluations of the safe and effective profile of the targeted fat-grafting technique for temporal hollowing augmentation. DESIGN, SETTING, AND PARTICIPATIONS: In a retrospective cohort study, a total of 96 consecutive patients with temporal hollowing were treated at the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai, China, with the targeted fat-grafting technique from January 1, 2009, to January 1, 2017. MAIN OUTCOMES AND MEASURES: The safety and efficacy profile of this technique was evaluated by the following methods: (1) a quantitative measurement of fat-graft survival and temporal augmentation rates by using 3-dimensional laser scanning, (2) a subjective assessment using a satisfaction survey and the Hollowness Severity Rating Scale (grades range from 0-3, with higher grades representing more hollowness), and (3) the complication rate. RESULTS: Of the 96 study patients, 94 (97.9%) were women and the mean (SD) age was 34.4 (7.4) years. Of the 142 autologous fat-grafting procedures performed, the mean (SD) total follow-up time was 16.3 (3.2) months, with a mean (SD) of 1.5 (0.7) procedures performed. The mean (SD) baseline volume requirement per temple for each patient was 12.8 (4.8) mL, and the total volume of the fat graft per temple was 17.8 (7.5) mL. Quantitative analysis revealed that the mean (SD) total augmentation volume per temple was 11.7 (3.0) mL, the total survival rate of the fat grafts was 65.7% (12.6%), and total augmentation rate of hollowness was 91.4% (23.4%). Subjective analysis revealed that all patients showed an improved appearance after fat grafting, and 142 temples (74.0%) exhibited clinical improvement by more than 2 grades. In all, 88 patients (91.7%) were satisfied with the outcomes, with a low complication rate reported. CONCLUSIONS AND RELEVANCE: The targeted fat-grafting technique allows the transplant of fat tissue into 4 separate fat compartments in a double-plane manner through a unique cannula entry site that avoids severe neurovascular injury. The long-term results demonstrate that this technique is an effective, reproducible, and safe approach for temporal hollowing augmentation. LEVEL OF EVIDENCE: 4.

IL-6 potentiates BMP-2-induced osteogenesis and adipogenesis via two different BMPR1A-mediated pathways.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used in the clinic for bone defect reconstruction because of its powerful osteoinductive capacity. However, commercially available rhBMP-2 requires a high concentration in the clinical setting for consistent bone formation. A high dose of rhBMP-2 induces a promising bone formation yield but also leads to inflammation-related events, deteriorated bone quality, and fatty tissue formation. We hypothesize that the seemingly contradictory phenomenon of coformation of new bone and excessive adipose tissue in rhBMP-2-induced bone voids may be associated with interleukin-6 (IL-6), which is significantly elevated after application of rhBMP-2/absorbable collagen sponge (rhBMP-2/ACS). Here, we show that IL-6 injection enhances new bone regeneration and induces excessive adipose tissue formation in an rhBMP-2/ACS-induced ectopic bone formation model in rats. In vitro data further show that IL-6 and its soluble receptor sIL-6R synergistically augment rhBMP-2-induced osteogenic and adipogenic differentiation of human BMSCs (hBMSCs) by promoting cell surface translocation of BMPR1A and then amplifying BMPR1A-mediated BMP/Smad and p38 MAPK pathways, respectively. Our study suggests elevated IL-6 may be responsible for coformation of new bone and excessive adipose tissue in rhBMP-2-induced bone voids.