Improving Facial Fat Graft Survival Using Stromal Vascular Fraction-Enriched Lipotransfer: A Multicenter Randomized Controlled Study.

BACKGROUND: Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multicenter randomized controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts. METHODS: Twenty-three participants were enrolled for autologous fat transfer in the face, and assigned randomly to the experimental ( n = 11) or control ( n = 12) group. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded. RESULTS: The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks, 74.5% ± 9.99% versus 66.55% ± 13.77%, P < 0.025; 24 weeks, 71.27% ± 10.43% versus 61.98% ± 13.46%, P < 0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks ( P < 0.023). Furthermore, graft survival in the forehead ( P < 0.021) and cheeks ( P < 0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group ( P < 0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted. CONCLUSION: SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Sequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration.

The clinical use of bioactive molecules in bone regeneration has been known to have side effects, which result from uncontrolled and supraphysiological doses. In this study, we demonstrated the synergistic effect of two bioactive molecules, bone morphogenic protein-2 (BMP-2) and alendronate (ALN), by releasing them in a sequential manner. Collagen-hydroxyapatite composite scaffolds functionalized using BMP-2 are loaded with biodegradable microspheres where ALN is encapsulated. The results indicate an initial release of BMP-2 for a few days, followed by the sequential release of ALN after two weeks. The composite scaffolds significantly increase osteogenic activity owing to the synergistic effect of BMP-2 and ALN. Enhanced bone regeneration was identified at eight weeks post-implantation in the rat 8-mm critical-sized defect. Our findings suggest that the sequential delivery of BMP-2 and ALN from the scaffolds results in a synergistic effect on bone regeneration, which is unprecedented. Therefore, such a system exhibits potential for the application of cell-free tissue engineering.

Enhanced predictive capacity using dual-parameter chip model that simulates physiological skin irritation.

Current alternatives to animal testing methods for skin irritation evaluation such as reconstructed human epidermis models are not fully representing physiological response caused by skin irritants. Skin irritation is physiologically induced by the dilation and increased permeability of endothelial cells. Thus, our objectives were to mimic physiological skin irritation using a skin-on-a-chip model and compare predictive capacities with a reconstructed human epidermis model to evaluate its effectiveness. To achieve our goals, the skin-on-a-chip model, consisting of three layers representing the epidermal, dermal and endothelial components, was adapted. Cell viability was measured using the OECD TG 439 protocol for test substance evaluation. The tight junctions of endothelial cells were also observed and measured to assess physiological responses to test substances. These parameters were used to physiologically evaluate cell-to-cell interactions induced by test substances and quantify model accuracy, sensitivity, and specificity. Based on in vivo data, the classification accuracy of twenty test substances using a dual-parameter chip model was 80%, which is higher than other methods. Besides, the chip model was more suitable for simulating human skin irritation. Therefore, it is important to note that the dual-parameter chip model possesses an enhanced predictive capacity and could serve as an alternative to animal testing for skin irritation.

Efficient reduction of fibrous capsule formation around silicone breast implants densely grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers by heat-induced polymerization.

Implants based on silicone elastomers, polydimethylsiloxane (PDMS), have been widely used for breast augmentation and reconstruction, but excessive foreign body reactions around implants often cause serious side effects such as capsular contracture. In our previous study, we covalently grafted 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymers on the surface of PDMS blocks by UV-induced polymerization and showed effective reduction of capsular formation around the MPC-grafted PDMS in rats. In the present study, we examined the efficacy of heat-induced polymerization of MPC grafting on silicone breast implants intended for humans, and analyzed the in vivo inhibitory effect against capsular formation and inflammation in pigs, which are closely related to humans in terms of epidermal structures and fibrotic processes. The heat-induced polymerization provided a thicker MPC-grafted surface and was more effective than UV-induced polymerization for the grafting of complex shaped non-transparent implants. After 24-week implantation in the submuscular pockets of Yorkshire pigs, the heat-induced MPC-grafted breast implants showed 45% smaller capsular thickness and 20-30% lower levels of inflammatory markers such as myeloperoxidase (MPO), transforming growth factor-ß (TGF-ß), and α-smooth muscle actin (α-SMA) in surrounding tissues compared to non-grafted implants. This study provides important information for future clinical trials of MPC-grafted silicone implants.

A Facial Recognition Mobile App for Patient Safety and Biometric Identification: Design, Development, and Validation.

BACKGROUND: Patient verification by unique identification is an important procedure in health care settings. Risks to patient safety occur throughout health care settings by failure to correctly identify patients, resulting in the incorrect patient, incorrect site procedure, incorrect medication, and other errors. To avoid medical malpractice, radio-frequency identification (RFID), fingerprint scanners, iris scanners, and other technologies have been implemented in care settings. The drawbacks of these technologies include the possibility to lose the RFID bracelet, infection transmission, and impracticality when the patient is unconscious. OBJECTIVE: The purpose of this study was to develop a mobile health app for patient identification to overcome the limitations of current patient identification alternatives. The development of this app is expected to provide an easy-to-use alternative method for patient identification. METHODS: We have developed a facial recognition mobile app for improved patient verification. As an evaluation purpose, a total of 62 pediatric patients, including both outpatient and inpatient, were registered for the facial recognition test and tracked throughout the facilities for patient verification purpose. RESULTS: The app was developed to contain 5 main parts: registration, medical records, examinations, prescriptions, and appointments. Among 62 patients, 30 were outpatients visiting plastic surgery department and 32 were inpatients reserved for surgery. Whether patients were under anesthesia or unconscious, facial recognition verified all patients with 99% accuracy even after a surgery. CONCLUSIONS: It is possible to correctly identify both outpatients and inpatients and also reduce the unnecessary cost of patient verification by using the mobile facial recognition app with great accuracy. Our mobile app can provide valuable aid to patient verification, including when the patient is unconscious, as an alternative identification method.

Biocompatibility and Efficiency of Biodegradable Magnesium-Based Plates and Screws in the Facial Fracture Model of Beagles.

PURPOSE: A biodegradable magnesium alloy system has been developed as a substitute for conventional plates and screws made of titanium or absorbable polymer. However, previous studies were limited to small animal experiments using screws or wires. In the present study, we preliminarily evaluated the biocompatibility and effectiveness of human standard-size biodegradable magnesium-based plates and screws in facial fractures of beagles. MATERIALS AND METHODS: Fracture lines were created bilaterally in the zygomatic arches of 6 beagles. They were fixed in situ with plates and screws made of magnesium alloy mixed with calcium and zinc (experimental group) or absorbable polymer (control group). Laboratory testing, radiologic imaging, histologic analysis, and mechanical testing were performed 4 weeks postoperatively. RESULTS: Inflammatory reactions were not significantly increased in any animal. Mechanical testing showed greater ultimate load and structural stiffness in the experimental group. In the histologic analysis, the void area and bone regeneration area were increased in the experimental, and the implant area and soft tissue area were increased in the control group. Radiologically, 3-dimensional micro-computed tomography showed no differences in the bone gap area between the 2 groups. A temporary increase in hydrogen gas around the magnesium implants regressed spontaneously and did not affect bone healing significantly. CONCLUSIONS: Magnesium-based biodegradable plates and screws showed good biocompatibility and offered considerable stability for fixating facial bone fractures in the early bone-healing process. These results show the possibilities for the future development of magnesium alloy plates and screws for craniomaxillofacial fixation in humans.

Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium.

BACKGROUND: Fibroblasts are ubiquitous cells in the human body and are absolutely necessary for wound healing such as for injured skin. This role of fibroblasts was the reason why we aimed to differentiate human adipose-derived stem cells (hADSCs) into fibroblasts and to test their wound healing potency. Recent reports on hADSC-derived conditioned medium have indicated stimulation of collagen synthesis as well as migration of dermal fibroblasts in wound sites with these cells. Similarly, human fibroblast-derived conditioned medium (F-CM) was reported to contain a variety of factors known to be important for growth of skin. However, it remains unknown whether and how F-CM can stimulate hADSCs to secrete type I collagen. METHODS: In this study, we obtained F-CM from the culture of human skin fibroblast HS27 cells in DMEM media. For an in-vivo wound healing assay using cell transplantation, balb/c nude mice with full-thickness skin wound were used. RESULTS: Our data showed that levels of type I pro-collagen secreted by hADSCs cultured in F-CM increased significantly compared with hADSCs kept in normal medium for 72 h. In addition, from a Sircol collagen assay, the amount of collagen in F-CM-treated hADSC conditioned media (72 h) was markedly higher than both the normal medium-treated hADSC conditioned media (72 h) and the F-CM (24 h). We aimed to confirm that hADSCs in F-CM would differentiate into fibroblast cells in order to stimulate wound healing in a skin defect model. To investigate whether F-CM induced hADSCs into fibroblast-like cells, we performed FACS analysis and verified that both F-CM-treated hADSCs and HS27 cells contained similar expression patterns for CD13, CD54, and CD105, whereas normal medium-treated hADSCs were significantly different. mRNA level  analysis for Nanog, Oct4A, and Sox2 as undifferentiation markers and vimentin, HSP47, and desmin as matured fibroblast markers supported the characterization that hADSCs in F-CM were highly differentiated into fibroblast-like cells. To discover the mechanism of type I pro-collagen expression in hADSCs in F-CM, we observed that phospho-smad 2/3 levels were increased in the TGF-ß/Smad signaling pathway. For in-vivo analysis, we injected various cell types into balb/c nude mouse skin carrying a 10-mm punch wound, and observed a significantly positive wound healing effect in this full-thickness excision model with F-CM-treated hADSCs rather than with untreated hADSCs or the PBS injected group. CONCLUSIONS: We differentiated F-CM-treated hADSCs into fibroblast-like cells and demonstrated their efficiency in wound healing in a skin wound model.

Skin-on-a-chip model simulating inflammation, edema and drug-based treatment.

Recent advances in microfluidic cell cultures enable the construction of in vitro human skin models that can be used for drug toxicity testing, disease study. However, current in vitro skin model have limitations to emulate real human skin due to the simplicity of model. In this paper, we describe the development of 'skin-on-a-chip' to mimic the structures and functional responses of the human skin. The proposed model consists of 3 layers, on which epidermal, dermal and endothelial components originated from human, were cultured. The microfluidic device was designed for co-culture of human skin cells and each layer was separated by using porous membranes to allow interlayer communication. Skin inflammation and edema were induced by applying tumor necrosis factor alpha on dermal layer to demonstrate the functionality of the system. The expression levels of proinflammatory cytokines were analyzed to illustrate the feasibility. In addition, we evaluated the efficacy of therapeutic drug testing model using our skin chip. The function of skin barrier was evaluated by staining tight junctions and measuring a permeability of endothelium. Our results suggest that the skin-on-a-chip model can potentially be used for constructing in vitro skin disease models or for testing the toxicity of cosmetics or drugs.