Short-term cryoprotectant-free cryopreservation at -20°C does not affect the viability and regenerative capacity of nanofat.

Nanofat is an autologous fat derivative with high regenerative activity, which is usually administered immediately after its generation by mechanical emulsification of adipose tissue. For its potential repeated use over longer time, we herein tested whether cryopreservation of nanofat is feasible. For this purpose, the inguinal fat pads of donor mice were processed to nanofat, which was i) frozen and stored in a freezer at -20°C, ii) shock frozen in liquid nitrogen with subsequent storage at -80°C or iii) gradually frozen and stored at -80°C. After 7 days, the cryopreserved nanofat samples were thawed and immunohistochemically compared with freshly generated nanofat (control). Nanofat frozen and stored at -20°C exhibited the lowest apoptotic rate and highest densities of blood and lymph vessels, which were comparable to those of control. Accordingly, nanofat cryopreserved at -20°C or control nanofat were subsequently fixed with platelet-rich plasma in full-thickness skin defects within dorsal skinfold chambers of recipient mice to assess vascularization, formation of granulation tissue and wound closure by means of stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over 14 days. These analyses revealed no marked differences between the healing capacity of wounds filled with cryopreserved or control nanofat. Therefore, it can be concluded that cryopreservation of nanofat is simply feasible without affecting its viability and regenerative potential. This may broaden the range of future nanofat applications, which would particularly benefit from repeated administration of this autologous biological product.

Corrigendum: Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

[This corrects the article DOI: 10.3389/fphar.2023.900205.].

The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial.

BACKGROUND: To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes. METHOD: This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects. CONCLUSION: In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.

Comparison the Effect of Conventional and Nanofat Injection Methods on Nasolabial Fold Lipofilling: A Case- Control Study.

Background: Nasolabial folds are a common sign of aging, accompanied by various manifestations such as skin and tissue loosening, wrinkles, lip corner drooping, mandibular angle loss, platysmal bands, and skin pigmentation changes. Limited research has explored Nanofat injection methods. this study was done with the aim of comparing the effect of fat injection by two methods, conventional and Nanofat, in nasolabial folds. Method: The study conducted in 2020-2021 at the skin clinic in Ilam, western Iran was a case-control study. Participants were divided into two groups, and lipofilling procedures were performed using conventional and nanofat methods with autologous fat. Data collection utilized a researcher-made questionnaire and radiographic results. Follow-up visits occurred on the 30th, 90th, and 180th days to assess complications and recovery rates. After 6 months, participant's photographs were taken and compared with pre-intervention photographs using the GIAS criteria. Data analysis was conducted using SPSS22 version software. Results: The average age of the participants was 37.80±8.30 yr. The treatment response in the conventional fat injection group was significantly better than the nanofat group (P<0.05). Both groups were satisfied with the treatment methods, but high satisfaction was reported in the conventional group, but there was no statistically significant difference between the groups. Conclusion: Both methods of improving wrinkles were effective, but the improvement and response to treatment in the conventional method was better than the Nanofat method, and its effect was felt by the participants for an average period of 3 months.

Autologous Nanofat Injection Combined with Fractional CO2 Laser in the Treatment of Atrophic Acne Scars.

Background: Atrophic acne scarring is a widely prevalent condition and one of the most distressing complications of acne vulgaris. Numerous options with variable outcomes are available for the treatment of acne scarring. Laser is considered a first-line therapy for acne scars, and recently there has been a growing interest in using stem cells and their derivatives for treating acne scars. In addition, combined therapeutic modalities often achieve more satisfactory results than a single treatment. Objective: We tried to evaluate the role of nanofat and fractional CO2 laser as a combined treatment approach for atrophic acne scarring. Methods: Twenty-five patients with atrophic acne scarring were enrolled. They received a single session of intradermal nanofat injection, at different points 1 cm apart, for acne scars. Two weeks later, they were treated with three sessions of fractional CO2 laser at monthly intervals. Patients were evaluated three months after the last session using the quantitative Goodman and Baron scoring system. Pain, side effects, and patients' satisfaction were also evaluated. Results: There were two males and 23 females with a mean age of 25.96 years. Their skin type ranged between Fitzpatrick skin type III, IV, and V. Boxcar scars were the most common scar type in 13 patients (52%). After treatment, there was a significant reduction (p <0.05) in the quantitative Goodman and Baron scores. The improvement was more evident in rolling scars. Seven patients reported significant improvement, and 12 reported marked improvement. Conclusion: This study showed that combining nanofat and fractional CO2 laser is a safe and effective treatment modality for atrophic acne scars.

Autologous nanofat harvested from donor site of full-thickness skin or skin flap grafting for the treatment of early postburn scarring: a case series.

Introduction: Postburn scarring often presents a specific reconstructive challenge from both functional and cosmetic perspectives. The purpose of this study was to investigate whether autologous nanofat harvested from the donor site of full skin or a skin flap can be reused for the treatment of early postburn scaring. Methods: From July 2018 to April 2022, patients with early postburn scarring underwent scar reconstruction surgery with full-thickness skin or a skin flap for a contour deformity and/or scar contracture, and autologous nanofat grafting was performed during the same operation. The Vancouver Scar Score (VSS) and the itch and pain scores were evaluated at the preoperation time point as well as at 2-3 weeks and 3-months postoperation. A comparison was made among the same patients at different time points. Results: A total of 17 patients, aged from 18 months to 62 years old were included in this analysis. The VSS was reduced from 10.00 ± 2.12 to 7.41 ± 1.277 at the 2-3-week postoperation time point, and to 5.53 ± 1.37 at the 3-month postoperation time point. The pain and itch score were reduced from 4.65 ± 1.37 and 6.35 ± 1.27, to 3.70 ± 1.10 and 4.94 ± 1.30 at the 2-3-week postoperation time point, and to 3.00 ± 1.28 and 3.94 ± 0.97 at the 3-month postoperation time point respectively. The VSS and pain and itch scores showed a statistically significant reduction (P < 0.05) at the 2-3-week and 3-month postoperative follow-ups compared with the preoperation time point. Conclusion: Autologous nanofat grafting from donor sites of full thickness skin or skin flap may be a promising treatment for an early postburn scaring as it promotes scar softening, improves itching and pain within the scar. However, this is a small case series with only 17 patients. Further conclusions need to be drawn through expanded samples for randomized controlled clinical trials. Lay Summary: Hypertrophic scarring is the most common complication after partial thickness burn injury, and the complex pathogenesis and prolonged dynamic process render treatments only marginally effective. In the past few decades, with the technological advances of liposuction and fat grafting, nanofat grafting has been used in a variety of surgical fields, including wound healing, scleroderma, facial rejuvenation, and neuralgia. However, the role of nanofat grafting is not well documented in the prevention and treatment of early postburn scarring. Full-thickness skin grafting or skin flap transplantation is the most common method for the reconstruction of a hypertrophic scaring until now. In the current study, we harvested subcutaneous fat during the preparation of the full-thickness skin or skin flap, prepared nanofat and injected it in the scar located at a nonsurgical site. Comparison of the pre- and postoperation scores for scar color, scar thickness, scar stiffness, and scar regularity showed that the postoperation scores were decreased significantly and that there was a significant improvement in scar pigmentation and thickness as well astheaesthetic outcome after treatment. Most importantly, reductions in the scores for pain and itching could be assessed objectively. It seems that the nanofat grafting is a potential method for prevention and treatment for early postburn scaring.

Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds.

The treatment of wounds using the body's own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)+ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP+ vascular and lymph vessel fragments, which interconnected with the GFP- vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management.

Histological Comparison of Nanofat and Lipoconcentrate: Enhanced Effects of Lipoconcentrate on Adipogenesis and Angiogenesis.

BACKGROUND: Nanofat and lipoconcentrate contain adipose-derived stem cells and growth factors, and have wide clinical applications in the regenerative field. This study aimed to investigate the microenvironmental changes associated with nanofat and lipoconcentrate. METHODS: Conventional fat, nanofat, or lipoconcentrate (0.2 mL each, n = 5 per group) were injected subcutaneously into the dorsal flanks of athymic nude mice. The graft weights were measured at postoperative week 4; the grafts and their overlying skin were used for histological analyses. RESULTS: Weights of the lipoconcentrate grafts were significantly greater than those of the conventional fat (p < 0.05) and nanofat (p < 0.01) grafts. There was no significant difference in inflammation, oil cysts, and fibrosis between the conventional fat and nanofat groups. Histological examination of the lipoconcentrate grafts showed less macrophage infiltration and the formation of fibrosis and oil cysts. Additionally, adipogenesis and angiogenesis were induced more in the lipoconcentrate grafts than in the nanofat grafts (p < 0.01). Lipoconcentrate and nanofat improved dermal thickness (p < 0.001 and p < 0.01, respectively, versus the baseline). CONCLUSION: Lipoconcentrate grafts had greater volume and shape retention than conventional fat and nanofat grafts. They had better histological structure and acted as scaffolds for adipogenesis and angiogenesis. Both products showed regenerative effects on dermal thickness; however, only lipoconcentrate grafts had the required volume and regenerative effects, allowing it to serve as a novel adipose-free grafting method for facial rejuvenation and contouring. 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 Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Fat transplant: Amazing growth and regeneration of cells and rebirth with the miracle of fat cells.

BACKGROUNDS AND OBJECTIVE: During fat transplantation, adipose tissue is removed from the body and injected into different areas under the skin. The goal of this review article is to look into the efficacy and applicability of fat transplantation in regenerative medicine and rejuvenation, including Nanofat, Microfat, and Millifat. METHODS: As a search strategy and study selection, we searched the PubMed and Medline databases until 2023 using related keywords (e.g., Nanofat, Microfat and Millifat, Regenerative Medicine, and Rejuvenation). RESULTS: Autologous fat transplantation has no risk of an allergic reaction or rejection of the transplant by the individual. Autologous adipose tissue is considered an ideal filler for facial rejuvenation and is suggested as the most biocompatible and non-immunogenic skin filler. Adipose tissue transplant may have semi-permanent to permanent effects. According to recent reports, adipose tissues possess a high percentage of mature stem cells. The effect of regenerating adipose tissue and its intrinsic cells can be described as an obvious process. Variations in the sizes of adipose tissues can result in different results depending on the surgical site. Based on topographic assessment, graft fats are assigned depending on the anatomical locations and the size such as Millifat (2-2.5 mm), Microfat (1 mm), and Nanofat (500 µm or less). CONCLUSION: Some characteristics of fat tissue increase its effectiveness, such as increasing stem cells, growth factors, cytokines, and compounds effective in repair, regeneration, and rejuvenation.

Toward facial rejuvenation; A clinical trial to assess the efficacy of nano fat grafting on wrinkles.

INTRODUCTION: With increasing age, patients' facial volume decrease. For this reason, nano fat grafting has recently gained popularity as adjunctive treatment to facial rejuvenation procedures. However, few quantitative studies have been conducted to investigate the impact of nano fat on facial wrinkles. AIMS: In the present study, authors aim to investigate the therapeutic effect of intradermal injection of nano fat on fine facial wrinkles and assess their changes over 7 months of follow-up. METHODS: In this randomized trial, 15 patients with fine facial wrinkles were enrolled. The fat was harvested from the abdomen and processed into nano fat. Nano fat was injected into the facial wrinkles intradermally with a needle of 27 gauge. The patients were evaluated before and 7 months postinjection utilizing Visio face 1000D (CK electronic, manufactured in Germany); and four parameters of wrinkles (area, volume, depth, and percent area) were evaluated before and after the nano fat injection. RESULTS: Our evaluation with Visio face showed that nano fat injection was significantly reduced the volume, area, depth, and percent area of wrinkles after 7 months of follow-up without serious long-lasting adverse effects. Moreover, wrinkles with higher percent area, depth and volume loss show greater improvement after the treatment. Our results also indicate that males and females equally benefit from this treatment except for the percent area parameter that was improved more significantly in male patients. CONCLUSION: Our study showed that intradermal injection of nano fat significantly decreases the volume, area, depth, and percent area of fine facial wrinkles. Further quantitative studies with control groups and larger sample sizes are required.

Stromal Vascular Fraction Gel (SVF-Gel) Combined with Nanofat for Tear Trough Deformity.

BACKGROUND: Tear trough deformity makes patients appear tired. Patients with less severe tear trough deformity prefer a less invasive method to correct the deformity. The infraorbital area is a multilayered tissue, and the aging of various components leads to tear trough deformity. To this end, we utilized the different characteristics of different fat derivatives to correct tear trough deformity. METHODS: Thirty-two patients with Barton Grade I/II tear trough deformity were enrolled in this study between September 2020 and March 2021. We injected Stromal Vascular Fraction Gel (SVF-Gel) into the suborbicularis oculi fat layer and Nanofat into the subcutaneous. After 12 months of follow-up, we evaluated the changes using standardized clinical photogrammetric techniques, volume, global aesthetic improvement scale, and patient self-evaluation. RESULTS: There were no major complications in any of the 32 patients. The measured data points demonstrated improvements in all aesthetic parameters. The width of the tear trough and the distance from the pupil to the tear trough improved. The Global Aesthetic Improvement Scale (GAIS) showed a high score (2.45±0.64 points), with patient self-assessment showing satisfactory results. CONCLUSION: SVF-Gel combined with Nanofat injection can effectively correct tear trough deformities. 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 .

Combined Synergetic Effect of Lipoconcentrate Fat Grafting, Nanofat Transfer, Platelet-Rich Plasma, Microneedling, and CO2 Fractional Laser for Plastic Regenerative and Esthetic Surgery and Cosmetic Care.

The advancements in skin care methods and products show the rising interest in cosmetics. Recent studies emphasize the regenerative potential of fat grafting, platelet-rich plasma (PRP), microneedling, and carbon dioxide (CO2) fractional laser techniques. Combining these strategies into a protocol is yet to be explored. In this article, we demonstrate different types of fat grafts and their versatility in treating different facial problems found in our patient. This study evaluated the synergistic effect of lipoconcentrate and nanofat grafting, PRP, microneedling, and CO2 fractional laser to provide esthetic and regenerative facial skin care. This case report was conducted in Dr. Soliman Fakeeh Hospital, Saudi Arabia. Our case involved a 53-year-old woman who had traumatic facial injuries due to a car accident years ago that buried asphalt particles in her facial scars, causing bluish skin discoloration. She suffered from multiple deep atrophic scars in several areas on the left side of her face, causing asymmetry. She was treated using lipoconcentrate and nanofat grafting, followed by three PRP with microneedling sessions and then a final CO2 fractional laser session. The evaluation was based on the physician's clinical assessment, image documentation, and patient satisfaction, which revealed significant improvement in skin appearance with respect to texture, color, symmetry, and overall health of the skin over a period of four months. The potentiality and efficacy of the combination therapy of lipoconcentrate, nanofat, PRP, microneedling, and CO2 fractional laser for skin rejuvenation and scar treatment showed promising results in this case report.

Lipoinjection with Adipose Stem Cells for Nasal Modeling: Rhino Cell, a Highly Versatile Alternative.

It is undeniable that a significant number of patients who want to improve their facial appearance is increasingly interested in nonsurgical procedures. Without a doubt, the use of autologous fat could not be left out as a magnificent alternative for nasal modeling simply because of four influential factors: ease of collection, compatibility, the temporality of the results, and safety. This work describes an innovative alternative technique for nasal modeling using micrografts enriched with adipose-derived mesenchymal stem cells (ASCs). With this technique, fat was collected and divided into two samples, nanofat and microfat. Nanofat was used to isolate the ASCs; microfat was enriched with ASCs and used for nasal modeling. Lipoinjection was performed in a supraperiosteal plane on the nasal dorsum. Through a retrolabial access, the nasal tip and base of the columella were lipoinjected. We consider that nonsurgical nasal modeling using micrografts enriched with ASCs can be an attractive and innovative alternative. This technique will never be a substitute for surgical rhinoplasty. It can be performed in a minor procedure area with rapid recovery and return to the patient's daily activities the next day. If necessary, the procedure can be repeated.

Nanofat in Plastic Reconstructive, Regenerative, and Aesthetic Surgery: A Review of Advancements in Face-Focused Applications.

Nanofat is a relatively novel technique in fat grafting that has gained significant interest in the fields of regenerative medicine, aesthetic and translational research. It involves the extraction of autologous fat from a patient, which is then transformed into "nanofat", consisting of small fat particles with a diameter of less than 0.1 mm and containing high concentrations of stem cells and growth factors. This article focuses on the use of nanofat in facial rejuvenation and its potential for lipomodelling. Fat tissue is a "stem cell depot" and nanofat contains many stem cells that can differentiate into various cell types. The Lipogem technology, developed in 2013, enables the isolation of nanofat with an intact perivascular structure, utilizing the high concentration of mesenchymal stromal cells near the pericytes of the adipose vascular system. Nowadays nanofat is used primarily for cosmetic purposes particularly in rejuvenating and improving the appearance of the skin, especially the face. Indeed, it has wide applicability; it can be used to treat fine lines, wrinkles, acne scars, sun-damaged skin, scar repair, and as an alopecia treatment. However, further studies are needed to assess the long-term efficacy and safety of this technique. In conclusion, nanofat is a safe and minimally invasive option for tissue regeneration with considerable therapeutic potential. This study reviews the application and effects of nanofat in regenerative medicine and facial cosmetic surgery.

Highly Pluripotent Adipose-Derived Stem Cell-Enriched Nanofat: A Novel Translational System in Stem Cell Therapy.

Fat graft is widely used in plastic and reconstructive surgery. The size of the injectable product, the unpredictable fat resorption rates, and subsequent adverse effects make it tricky to inject untreated fat into the dermal layer. Mechanical emulsification of fat tissue, which Tonnard introduced, solves these problems, and the product obtained was called nanofat. Nanofat is widely used in clinical and aesthetic settings to treat facial compartments, hypertrophic and atrophic scars, wrinkle attenuation, skin rejuvenation, and alopecia. Several studies demonstrate that the tissue regeneration effects of nanofat are attributable to its rich content of adipose-derived stem cells. This study aimed to characterize Hy-Tissue Nanofat product by investigating morphology, cellular yield, adipose-derived stem cell (ASC) proliferation rate and clonogenic capability, immunophenotyping, and differential potential. The percentage of SEEA3 and CD105 expression was also analyzed to establish the presence of multilineage-differentiating stress-enduring (MUSE) cell. Our results showed that the Hy-Tissue Nanofat kit could isolate 3.74 × 104 ± 1.31 × 104 proliferative nucleated cells for milliliter of the treated fat. Nanofat-derived ASC can grow in colonies and show high differentiation capacity into adipocytes, osteocytes, and chondrocytes. Moreover, immunophenotyping analysis revealed the expression of MUSE cell antigen, making this nanofat enriched of pluripotent stem cell, increasing its potential in regenerative medicine. The unique characteristics of MUSE cells give a simple, feasible strategy for treating a variety of diseases.

In vivo evaluation of Adipose-Derived Stem Cells (ADSCs) using Nanofat technique and chitosan conduit for peripheral nerve defect repair.

INTRODUCTION: Nerve autograft is the gold standard for reconstruction of peripheral nerve loss. The alternative is the interposition of a synthetic regeneration conduit. The purpose of the study was to evaluate the in vivo feasibility and interest of Adipose-Derived Stem Cells (ADSCs) using the Nanofat technique and chitosan conduit for peripheral nerve defect repair. MATERIAL AND METHODS: In vivo, after the creation of a 10 mm defect of the sciatic nerve, 2 groups were defined according to the nerve repair in rats: "chitosan" group (n = 10) and "chitosan and ADSCs" group (n = 10) with a clinical and paraclinical evaluation at 7 weeks. RESULTS: The in vivo results seem to show that the adjunction of ADSCs was favorable clinically, histologically and functionally compare to a chitosan reconstruction alone. DISCUSSION: Peripheral nerve repair with defect using a chitosan conduit associated with ADSCs would constitute a surgical alternative in a single surgical step.

Nanofat lysate ameliorates pain and cartilage degradation of osteoarthritis through activation of TGF-ß-Smad2/3 signaling of chondrocytes.

Introduction: Nanofat is an effective cell therapy for osteoarthritis (OA). However, it has clinical limitations due to its short half-life. We developed Nanofat lysate (NFL) to overcome the defect of Nanofat and explore its anti-OA efficacy and mechanism. Methods: Monoiodoacetate (MIA) was employed to establish rat OA model. For pain assessment, paw withdrawal latency (PWL) and thermal withdrawal latency (TWL) were evaluated. Degeneration of cartilage was observed by histopathological and immunohistochemical examination. Primary chondrocytes were treated with TNF-α to establish the cellular model of OA. MTT, wound healing, and transwell assays were performed to assess effects of NFL on chondrocytes. RNA-seq, qPCR and Western blot assays were conducted to clarify the mechanism of NFL. Results and Discussion: The animal data showed that PWL and TWL values, Mankin's and OARSI scorings, and the Col2 expression in cartilage were significantly improved in the NFL-treated OA rats. The cellular data showed that NFL significantly improved the proliferation, wound healing, and migration of chondrocytes. The molecular data showed that NFL significantly restored the TNF-α-altered anabolic markers (Sox9, Col2 and ACAN) and catabolic markers (IL6 and Mmp13). The RNA-seq identified that TGF-ß-Smad2/3 signaling pathway mediated the efficacy of NFL, which was verified by qPCR and Western blot that NFL significantly restored the abnormal expressions of TGFßR2, phosphorylated-Smad2, phosphorylated-Smad2/3, Col2, Mmp13 and Mmp3. After long-term storage, NFL exerted similar effects as its fresh type, indicating its advantage of storability. In sum, NFL was developed as a new therapeutic approach and its anti-OA efficacy and mechanism that mediated by TGF-ß-Smad2/3 signaling was determined for the first time. Besides, the storability of NFL provided a substantial advantage than other living cell-based therapies.

[Treatment of mild hemifacial microsomia in children by autologous nano-fat mixed granule fat transplantation].

Objective: To investigate the effectiveness of autologous nano-fat mixed granule fat transplantation in the treatment of facial soft tissue dysplasia in children with mild hemifacial microsomia (HFM). Methods: A total of 24 children with Pruzansky-Kaban type Ⅰ HFM were admitted between July 2016 and December 2020. Among them, 12 children were treated with autologous nano-fat mixed granule fat (1∶1) transplantation as study group and 12 with autologous granule fat transplantation as control group. There was no significant difference in gender, age, and affected side between groups ( P>0.05). The child's face was divided into region Ⅰ(mental point-mandibular angle-oral angle), region Ⅱ (mandibular angle-earlobe-lateral border of the nasal alar-oral angle), region Ⅲ (earlobe-lateral border of the nasal alar-inner canthus-foot of ear wheel). Based on the preoperative maxillofacial CT scan+three-dimensional reconstruction data, the differences of soft tissue volume between the healthy and affected sides in the 3 regions were calculated by Mimics software to determine the amount of autologous fat extraction or grafting. The distances between mandibular angle and oral angle (mandibular angle-oral angle), between mandibular angle and outer canthus (mandibular angle-outer canthus), and between earlobe and lateral border of the nasal alar (earlobe-lateral border of the nasal alar), and the soft tissue volumes in regions Ⅰ, Ⅱ, and Ⅲ of healthy and affected sides were measured at 1 day before operation and 1 year after operation. The differences between healthy and affected sides of the above indicators were calculated as the evaluation indexes for statistical analysis. At 1 year after operation, the parents, the surgeons, and the nurses in the operation group made a self-assessment of satisfaction according to the frontal photos of the children before and after operation. Results: The study group and the control group were injected with (28.61±8.59) and (29.33±8.08) mL of fat respectively, with no significant difference ( t=0.204, P=0.840). After injection, 1 child in the control group had a little subcutaneous induration, and no related complications occurred in the others. All children in both groups were followed up 1 year to 1 year and 6 months, with an average of 1 year and 4 months in the study group and 1 year and 3 months in the control group. At 1 year after operation, the asymmetry of the healthy and affected sides improved in both groups; the satisfactions of parents, surgeons, and nurses in the study group were all 100% (12/12), while those of the control group were 100% (12/12), 83% (10/12), and 92% (11/12), respectively. The differences between healthy and affected sides in mandibular angle-oral angle, mandibular angle-outer canthus, earlobe-lateral border of the nasal alar, and the soft tissue volume in 3 regions of the two groups after operation were significantly smaller than those before operation ( P<0.05). There was no significant difference in the above indexes between the two groups before operation ( P>0.05). After operation, all indexes were significantly lower in study group than in control group ( P<0.05). Conclusion: Autologous nano-fat mixed granule fat transplantation and autologous granule fat transplantation can both improve the facial soft tissue dysplasia in children with mild HFM, and the former is better than the latter.

Corrección de ojeras y del surco nasoyugal con Nanofat / Correction of dark circles and nasojugal sulcus with Nanofat

Introducción: El envejecimiento periorbitario se considera un proceso complejo y multifactorial que se relaciona con procesos intrínsecos y extrínsecos tales como los cambios degenerativos en la piel, la aparición de líneas finas, la pérdida de volumen, el descenso de tejidos, la piel flácida y el exceso de depósito de grasa. Objetivo: Evaluar los resultados de la corrección de las ojeras y del surco nasoyugal con Nanofat. Métodos: Se realizó un estudio longitudinal prospectivo en el Servicio de Cirugía Plástica y Caumatología del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" desde agosto de 2019 a mayo de 2021. La muestra la constituyeron 37 pacientes. Los datos se resumieron en frecuencias absolutas y relativas. Resultados: La edad promedio fue 47,2 ± 10,7 años. El 89,2 por ciento de los pacientes eran mujeres. La media del tejido emulsionado infiltrado por cada lado fue de 1,40 ± 0,4 ml, con un volumen mínimo de 1 ml y un máximo de 2 ml. En el 83,8 por ciento de los casos se constató una disminución del surco nasoyugal y en el 16,2 por ciento se evidenció una gran mejoría. En el 100 por ciento de los pacientes hubo avance de la hiperpigmentación y mejoría de la calidad de la piel. Dentro de las complicaciones solo un paciente (2,7 por ciento) presentó nódulos por calcificación en la zona receptora. El resto de los pacientes en estudio no presentó eventos adversos. El grado de satisfacción postratamiento con Nanofat fue de 100 por ciento. Conclusiones: Los resultados de la corrección de las ojeras y del surco nasoyugal con Nanofat son muy buenos(AU)

Introduction: Periorbital aging is considered a complex and multifactorial process that is related to intrinsic and extrinsic processes such as degenerative changes in the skin, appearance of fine lines, volume loss, tissue descent, sagging skin, and excess fat deposition. Objetive: To evaluate the results of correction of dark circles under the eyes and the nasojugal sulcus with Nanofat. Methods: A prospective longitudinal study was performed in the Plastic Surgery and Caumatology Service of the Clinical Surgical Hospital "Hermanos Ameijeiras" from August 2019 to May 2021. The sample consisted of 37 patients. The data were summarized in absolute and relative frequencies. Results: The mean age was 47.2±10.7 years. The 89.2 percent of the patients were women. The mean emulsified tissue infiltrated per side was 1.40±0.4 ml, with a minimum volume of 1 ml and a maximum of 2 ml. In 83.8 percent of the cases there was a decrease in the nasojugal sulcus and in 16.2 percent there was a great improvement. In 100 percent of the patients there was improvement of hyperpigmentation and great improvement of skin quality. Among the complications only one patient (2.7 percent) presented nodules due to calcification in the recipient area. The rest of the patients in the study did not present adverse events. The degree of post-treatment satisfaction with Nanofat was 100 percent. Conclusions: The results of correction of dark circles and nasojugal sulcus with Nanofat are very good(AU)

The LipoDerm Method for Regeneration and Reconstruction in Plastic Surgery: A Technical Experimental Ex Vivo Note.

The combination of adipose-derived stem cells (ASCs) and dermal scaffolds has been shown to be an approach with high potential in soft tissue reconstruction. The addition of dermal templates to skin grafts can increase graft survival through angiogenesis, improve regeneration and healing time, and enhance the overall appearance. However, it remains unknown whether the addition of nanofat-containing ASCs to this construct could effectively facilitate the creation of a multi-layer biological regenerative graft, which could possibly be used for soft tissue reconstruction in the future in a single operation. Initially, microfat was harvested using Coleman's technique, then isolated through the strict protocol using Tonnard's technique. Finally, centrifugation, emulsification, and filtration were conducted to seed the filtered nanofat-containing ASCs onto Matriderm for sterile ex vivo cellular enrichment. After seeding, a resazurin-based reagent was added, and the construct was visualized using two-photon microscopy. Within 1 h of incubation, viable ASCs were detected and attached to the top layer of the scaffold. This experimental ex vivo note opens more dimensions and horizons towards the combination of ASCs and collagen-elastin matrices (i.e., dermal scaffolds) as an effective approach in soft tissue regeneration. The proposed multi-layered structure containing nanofat and dermal template (Lipoderm) may be used, in the future, as a biological regenerative graft for wound defect reconstruction and regeneration in a single operation and can also be combined with skin grafts. Such protocols may optimize the skin graft results by creating a multi-layer soft tissue reconstruction template, leading to more optimal regeneration and aesthetic outcomes.