Mechanical stretch preconditioned adipose-derived stem cells elicit polarization of anti-inflammatory M2-like macrophages and improve chronic wound healing.

Transplantation of adipose-derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti-inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M-CSF) from ASCs, a chemokine that is linked to anti-inflammatory M2-like macrophages polarization. When the MS-ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS-ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.

Development of a Semifascicle Graft Technique to Bridge Peripheral Nerve Defect: A Case Report and Animal Study.

BACKGROUND: Autologous nerve grafting, the criterion standard for bridging peripheral nerves, can cause complications at the donor site. We investigated a novel approach to reconstruct the nerve gap with a split cross-sectional unmatched semifascicle autograft, which was harvested from the distal part of the injured nerve. METHODS: A patient diagnosed with left-sided frontal branch facial nerve dissection underwent nerve bridging emergency surgery using a semifascicle nerve graft. A sciatic nerve model was used to validate the feasibility and mechanism of this method. Male Sprague-Dawley rats (n = 36) were randomized into (A) intact fascicle, (B) semifascicle, and (C) semifascicle + conduit groups and further subdivided into 4- and 8-week groups for histological analysis of the neurotissue area, fibers, and Schwann cells. The 8-week groups underwent weekly pain and temperature tests; the wet weight of the gastrocnemius muscle was measured after euthanasia. RESULTS: The frontalis of the patient's injured side exhibited movement at 2 months postsurgery and recovered a symmetrical appearance at 13 months. Group A exhibited more neurotissue areas and fibers than groups B and C at week 4; group B had more neurotissue than group C. Group A had greater neurotissue areas than groups B and C at week 8; groups B and C exhibited no differences. The groups displayed no differences regarding nerve fiber, pain, and temperature analysis at week 8. Muscle wet weight of groups A and B exhibited no differences and was higher than that of group C. CONCLUSION: We demonstrated the clinical translational value of semifascicle nerve grafts; the injured site was both the donor and recipient, thereby avoiding donor site damage and associated complications.

Changes in Facial Symmetry Following Computer-Assisted Secondary Correction of Craniofacial Fractures.

OBJECTIVE: For patients without dysfunctions, the main purpose of secondary correction for craniofacial fractures is restoring facial symmetry. Computer-assisted surgery techniques including virtual surgical planning and intraoperative navigation provide the help to restore the bony symmetry as much as possible. The authors retrospectively quantitatively analyzed patients who received computer-assisted secondary correction for craniofacial fractures on facial symmetry pre and postoperation. METHODS: This observational study reviewed the medical records of 17 patients requiring secondary correction for craniofacial fractures. Pre and postoperative computed tomography data were used to quantitatively analyze the changes in facial symmetry and enophthalmos. RESULT: All patients enrolled in this study showed mid-facial asymmetry but without dysfunctions except for enophthalmos, and 5 patients had bone defects in the frontal-temporal area. The corrective surgical techniques were different for each patient according to their specific condition. Virtual surgical planning with or without intraoperative navigation was performed for all patients. Compared with the preoperative condition, their facial symmetry was significantly improved. The maximum discrepancy value between the affected side and the mirrored unaffected side decreased from 8.10 ± 2.69 to 3.74 ± 2.02 mm postoperatively, and the mean discrepancy value decreased from 3.58 ± 1.29 to 1.57 ± 0.68 mm. In addition, the Enophthalmos Index decreased from 2.65 to 0.35 mm. CONCLUSION: This observational study objectively demonstrated that computer-assisted secondary correction for craniofacial fractures can significantly improve facial symmetry. And the authors recommend that virtual surgical planning and intraoperative navigation should be a must step in craniofacial fracture correction.

Classification of Alar Dynamic Aesthetic in an Asian Female Population: Experts or Automatic Algorithms?

AIM: To provide referenced classifications of alar dynamic aesthetics from both subjective and objective perspectives for determining proper surgical strategies in alarplasty. METHODS: A total of 150 healthy Asian female participants were instructed to perform two standardized facial movements including a resting pose and a maximum smile while taking care not to show their teeth. The participants were recorded using a dynamic three-dimensional surface imaging system. Frames depicting the resting position and the alar maximum enlargement during the smile were exported separately for anthropometric analysis and classification. The alar dynamic aesthetic was assessed through measurement of the anthropomorphic changes comparing the resting and maximum smile statuses and then transformed into quantitative analysis through the algorithm [Formula: see text]. Subjective classification and evaluation of the subject cosmetic deficiencies and proposals for therapeutic interventions to improve the subjects' alar dynamic aesthetic were performed by three senior plastic surgeons through visualization of the resting and smiling images. The surgeons were asked to divide and classify the subjects into three groups (Class I, Class II and Class III) according to the surgeons' perceptions of degree of the subjects' deficiencies in alar dynamic aesthetic. The more deficiency there was in the aesthetic, the higher the class that the subject was assigned into. The surgeons were presented with the full set of images of the patients on two separate occasions each three months apart, to assess interobserver reliability. Clustering analysis, which is based on machine learning, was applied for objective classification of the images. RESULTS: According to the senior plastic surgeon experts' subjective classification, the subjects' alar flaring mobility was judged as follows: Class I (6.78 ± 3.84%), Class II (10.35 ± 4.18%), and Class III (18.68 ± 4.15%), while alar base mobility was judged as Class I (12.71 ± 7.57%), Class II (20.06 ± 10.06%), and Class III (30.86 ± 13.20%). By clustering analysis, alar flaring mobility was determined to be Class I (7.01 ± 3.51%), Class II (11.18 ± 4.76%), and Class III (12.72 ± 5.66%), while alar base mobility was Class I (9.07 ± 4.23%), Class II (21.88 ± 4.25%), and Class III (38.59 ± 7.08%). No statistical significance was found in the distribution and assignment of classes between the two methodologies. CONCLUSION: Classifications of alar dynamic aesthetics could arouse attention to facial dynamic aesthetics and provide referenced quantitative parameters for plastic surgeons to determine appropriate treatments for alarplasty. For patients with Class I mobility, treatments are not recommended, while minimally invasive treatments can be deemed to be optional for patients with Class II alar mobility to potentially improve alar dynamic aesthetics. For patients with Class III alar mobility, surgical treatments are strongly recommended as options. Combing subjective classification with automated algorithms can provide a novel perspective and improve reliability for facial aesthetic classification analysis. 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 .

Application of Segmented Template in Three-Dimensionally Guided Mandibular Angle Osteotomy.

BACKGROUND: The procedure of mandibular angle osteotomy (MAO) via an intraoral approach is challenging and experience-dependent due to the limited field of view and inadequate operational space. Uncertainty about the osteotomy line and plane can lead to severe complications. A three-dimensional printed guidance template based on a computer-assisted preoperative simulation is a potential solution to this problem. The current study aims to retrospectively investigate the feasibility and accuracy of using a custom-made segmented template to guide the osteotomy plane during the procedure. METHODS: Sixty patients who had segmented template-guided MAO were included in the study. Preoperative simulation using the custom-designed template and postoperative computed tomography were collected and parameters, including mandibular angle, gonion distance, and the mandibular plane angle were measured. A paired t tests and intraclass correlation coefficients (ICCs) were used to evaluate the efficacy, accuracy, and symmetry of the results. All complications were reviewed. RESULTS: The patients had a significantly larger mandibular angle and narrower gonion distance postoperatively. Preoperative simulations and postoperative outcomes were compared; ICCs were larger than 95% indicating significant agreement. Bilateral postoperative comparisons of the mandible also demonstrated excellent agreement (ICC > 95%). Numbness in the chin area was the most frequent complication but all recovered by 3 months postoperatively. CONCLUSIONS: The custom-made template can guide the osteotomy plane during the MAO procedure and achieve favorable accuracy and symmetry. Direct contact of the saw with the guidance template not only facilitates control of the osteotomy line but also the oblique angle of the osteotomy plane. This methodology may be a feasible and effective tool for mandibular contouring.

A Single-Blinded Prospective Study on Using Botulinum Toxin Type A for Reducing Alar Mobility.

BACKGROUND: With widespread utilization of instant social media, people desire a minimally invasive treatment to improve alar dynamic aesthetic, but few practical procedures on reducing alar mobility have been conducted. OBJECTIVES: This study aimed to verify the effects of botulinum toxin on reducing nasal alar mobility and provide a supplemental treatment of rhinoplasty. METHODS: This single-blind prospective study included a cohort of 20 participants with the desire to improve their alar dynamic aesthetic. The experimental group was injected with 3U botulinum toxin type A at dilator naris anterior, dilator naris vestibularis, levator labii superioris alaeque nasi, and dilator naris, and the control group received the equivalent of saline. Standardized facial movement (from rest to maximum smile without revealing teeth) was recorded with a 3-dimensional imaging system. The changes between rest and maximum smile statuses represented alar mobility and were generated by MOBILITY=WIDTHsmile-WIDTHrestWIDTHrest×100 % . Alar mobility and root mean square analysis were employed for postoperative evaluations. RESULTS: In the experimental group, alar flaring mobility decreased from 10.05% ± 6.40% to 4.91% ± 3.48%(P < 0.05), and alar base mobility decreased from 16.83% ± 5.69% to 12.50% ± 4.89% (P < 0.05), whereas no significant changes in alar mobility were found in the control group. In root mean square analysis, changes in the experimental group were significantly higher than in the control group (P < 0.05). CONCLUSIONS: Botulinum toxin type A can effectively restrain alar mobility without any significant adverse events and improve alar dynamic esthetic, which can serve as a minimally invasive method or supplemental treatment for rhinoplasty.

Hand Rejuvenation by Targeted Volume Restoration of the Dorsal Fat Compartments.

BACKGROUND: Recent anatomic findings suggest aging-related changes of the complex fat distribution in the hand. OBJECTIVES: To rejuvenate the aging hand, we developed a targeted fat grafting technique based on the physiologic fat distribution of the hand. METHODS: The dorsum of both hands was examined in 30 healthy volunteers of different age utilizing B-mode ultrasound to determine physiological changes of the aging hand. Additional anatomic dissection was performed in 10 hands of five fresh cadavers to establish the anatomic basis for the targeted restoration technique. A total of 17 patients were treated for hand rejuvenation utilizing this technique and followed up for at least 6 months. The posttreatment outcome was assessed through B-mode ultrasound, 3-dimensional (3D) topography scanning, and a patient satisfaction survey. RESULTS: According to the fat distribution of the dorsum, hand aging was divided into three grades: (1) mild atrophy with rhytides; (2) moderate atrophy with exposed veins; and (3) serious atrophy with exposed tendons. Anatomic findings showed the existence of distinct superficial and deep fat compartments. The average fat grafting volume was 25.5 ml per hand dorsum administered in one or two procedures. Patients were monitored for 8.3 ± 2.6 months. After 6 months, a volume gain was found in all patients. The degree of aging was significantly reduced. The majority of patients (94.1%) were satisfied with their results. CONCLUSIONS: This study provides the anatomic and clinical basis for targeted restoration of the physiological fat volume in the hand dorsum with high satisfaction rates. LEVEL OF EVIDENCE: 4.

Efficacy and Safety of Expanded Polytetrafluoroethylene Implantation in the Correction of Long-Term Posttraumatic Enophthalmos.

SUMMARY: Long-term enophthalmos is a common orbital fracture sequela. Various autografts and alloplastic materials have been studied in posttraumatic enophthalmos repair. However, expanded polytetrafluoroethylene (ePTFE) implantation in late enophthalmos repair has rarely been reported. The authors report novel use of ePTFE for late posttraumatic enophthalmos repair. This retrospective study included patients with posttraumatic long-term enophthalmos who underwent hand-carved ePTFE intraorbital implantation for enophthalmos correction. Computed tomography data were collected preoperatively and at follow-up. The volume of ePTFE, the degree of proptosis (DP), and enophthalmos were measured. Postoperative and preoperative DP and enophthalmos were compared using the paired t test. The correlation between ePTFE volume and DP increment was established using linear regression. Complications were identified by chart review. From 2014 to 2021, 32 patients were included, with a mean follow-up of 19.59 months. The mean volume of implanted ePTFE was 2.39 ± 0.89 mL. After surgery, the DP of the affected globe improved significantly, from 12.75 ± 2.12 mm to 15.06 ± 2.50 mm ( P < 0.0001). A significant linear correlation was found between ePTFE volume and DP increment ( P < 0.0001). Enophthalmos was substantially ameliorated from 3.35 ± 1.89 mm to 1.09 ± 2.07 mm ( P < 0.0001). Twenty-five patients (78.23%) had postoperative enophthalmos of less than 2 mm. Infection and implant dislocation were not observed. The authors concluded that ePTFE intraorbital implantation exhibited long-term efficacy and safety for late posttraumatic enophthalmos repair and represents an effective and predictable alternative. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Effects of repeated transection and coaptation of peripheral nerves on axonal regeneration and motoneuron survival.

BACKGROUND AND PURPOSE: Salvage procedures for facial reanimation can involve a second neurorrhaphy operation. It remains unclear whether reuse of the original donor nerve in the salvage procedure remains likely to produce successful outcome. This study aimed to investigate the effect of repeated transection and coaptation of a nerve on axonal regrowth and motoneuron survival. MATERIALS AND METHODS: The sciatic nerves of Sprague Dawley rats were transected and microsutured once (the one-time group) or repeatedly at eight-week intervals (the repeated group), and the animals remained alive for eight weeks before sacrifice. The gastrocnemius muscle was weighed, and muscle fiber diameter was measured with hematoxylin-eosin staining. Axonal count of the distal nerve stump was calculated by toluidine blue staining. Myelin thickness and axonal diameter were analyzed by transmission electronic microscopy. Finally, motoneurons were retrogradely traced to the spinal cord using Fluoro-Gold. RESULTS: Repeated coaptation of nerves resulted in significant decreases of the wet weight ratio of gastrocnemius and muscle fiber diameter. The axonal counts and myelin thicknesses of the distal stumps were comparable between the groups, whereas axonal diameter was significantly smaller after repeated injury. Additionally, retrograde tracing demonstrated significantly less motoneurons in the L4-L6 spinal segments of the repeatedly injured animals than that of the one-time group. CONCLUSIONS: Compared with one-time nerve injury, repetitive transection and coaptation of nerves resulted in compromised axonal regeneration, motoneuron survival, and target muscle recovery. It is possible that the final functional outcome could also be compromised, and the patients should be counseled accordingly.

A Novel Model for Cutaneous Wound Healing and Scarring in the Rat.

BACKGROUND: Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats. METHODS: Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching. RESULTS: Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar-related molecule expression, and distorted collagen arrangement in rat tail scars. CONCLUSIONS: The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.

Flavones hydroxylated at 5, 7, 3' and 4' ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity.

Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substitution reduced collagen expression most efficiently. Among those flavones, luteolin, quercetin, and myricetin were selected for follow-up. In vivo, the three compounds ameliorated skin fibrosis and reduced collagen deposition. Further analysis showed the compounds had significant inhibition on the proliferation, activation and contractile ability of dermal fibroblasts in vitro and in vivo. More importantly, we revealed that luteolin, quercetin, and myricetin selectively downregulated the phosphorylation of Smad2/3 in TGF-ß/Smads signaling via binding to activin receptor-like kinase 5 (ALK5) and impairing its catalytic activity. We also found flavones with 5, 7, 3', 4' hydroxy substitution showed stronger affinity with ALK5 compared with other flavonoids. Herein, we identified at least in part the underlying molecular basis as well as the critical structures that contribute to the antifibrotic bioactivity of flavones, which might benefit drug design and modification.

Facial Contouring by Targeted Restoration of Facial Fat Compartment Volume: The Midface.

BACKGROUND: Recent anatomical findings have suggested that facial fat distribution is complex and changes with age. Here, the authors developed a grafting technique based on the physiologic distribution and volume changes of facial fat compartments to achieve a youthful and natural-appearing face. METHODS: Forty cadaveric hemifaces were used for the dissection of fat compartments and neurovascular structures in the midface area. Seventy-eight patients were treated for cheek atrophy using the authors' targeted restoration of midface fat compartment volume. The outcome was evaluated by a two-dimensional assessment, malar lipoatrophy assessment, and a satisfaction survey. RESULTS: The medial and lateral parts of the deep medial cheek fat compartment were separated by a septum arising from the lateral border of the levator anguli oris muscle. The angular vein traveled between the deep medial cheek fat compartment and the buccal fat pad, 12 mm from the maxilla. A total volume of 29.3 ml of fat was grafted per cheek for each patient. A 12-month follow-up revealed an average volume augmentation rate of 27.1 percent. Pleasing and elevated anterior projection of the cheek and ameliorated nasolabial groove were still obvious by 12 months after the procedure. In total, 95.2 percent of the patients were satisfied with their results. CONCLUSIONS: The present study provides the anatomical and clinical basis for the concept of compartmentally based fat grafting. It allows for the restoration of facial fat volume close to the physiologic state. With this procedure, a natural and youthful facial contour could be rebuilt with a high satisfaction rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.