Bioactive decellularized adipose matrix prepared using a rapid, nonchemical/enzymatic method for adipogenesis.

Recent developments in the field of regenerative surgeries and medical applications have led to a renewed interest in adipose tissue-enriched mesenchymal stem cell scaffolds. Various advantages declared for the decellularized adipose matrix (DAM) have caused its extensive use in the transfer of stem cells or growth factors for soft tissue regeneration induction. Meanwhile, the long-term application of detergents toward DAM regeneration has been assumed as a risky obstacle in this era. Herein, a rapid, mechanical protocol was developed to prepare DAM (M-DAM) without chemicals/enzymes and was comprehensively compared with the ordinary DAM (traditional chemical method). Accordingly, this method could effectively hinder oils and cells, sustain the structural and biological elements, and contain a superior level of collagen content. In addition, more protein numbers, as well as higher basement membrane elements, glycoproteins, and extracellular matrix-related proteins were detected in the regenerated M-DAM. Also, superior adipogenesis and angiogenesis proteins were distinguished. The noncytotoxicity of the M-DAM was also approved, and a natural ecological niche was observed for the proliferation and differentiation of stem cells, confirming its great potential for vascularization and adipogenesis in vivo. The suggested technique could effectively prepare the modified DAM in variant constructions of tablets, powders, emulsions, hydrogels, and different three-dimensional-printed structures. Hence, this rapid, mechanical process can produce bioactive DAM, which has the potential to be widely used in various research fields of regenerative medicine.

Immediate SVF-Gel Injection Reduced Incision Scar Formation: A Prospective, Double-Blind, Randomized, Self-control Trial.

BACKGROUND: Skin incision scars are cosmetically displeasing; the effects of current treatments are limited, and new methods to reduce scar formation need to be found. OBJECTIVE: We sought to determine whether immediate postoperative injection of stromal vascular fraction gel (SVF-gel) could reduce scar formation at skin incision sites. METHODS: A prospective, randomized, double-blind, self-controlled trial was conducted in patients who underwent breast reduction. SVF-gel was intradermally injected into the surgical incision on one randomly selected side, with the other side receiving saline as a control. At the 6-month follow-up, the incision scars were evaluated using the Vancouver scar scale (VSS) and visual analog scale (VAS). Antera 3D camera was used for objective evaluation. RESULTS: The VSS score and VAS score were significantly different between the SVF-gel-treated side (3.80 ± 1.37, 3.37±1.25) and the control side (5.25 ± 1.18, 4.94 ± 1.28). Moreover, the SVF-gel-treated side showed statistically significant improvements in scar appearance, based on evidences from Antera 3D camera. LIMITATIONS: This was a single-center, single-race, and single-gender study. Furthermore, the results were available only for the 6-month interim follow-up period. CONCLUSION: Postoperative immediate SVF-gel injection in surgical incisions can reduce scar formation, and exert a preventive effect on scars. LEVEL OF EVIDENCE I: Evidence obtained from at least one properly designed randomized controlled trial. 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 .

Dual Network Hydrogels Based on PRP and SA Promote the Retention Rate and Vascularization of Transplanted Fat.

BACKGROUND: Autologous adipose tissue often experiences ischemia and hypoxia after transplantation, leading to low retention rates and unstable operative impacts due to necrotic absorption. Platelet-rich plasma (PRP) can enhance fat regeneration and increase the fat retention rate after transplantation. However, the quick release of growth factors (GFs) in PRP decreases therapeutic efficiency. This study aimed to achieve a slow release of PRP to promote fat retention. METHODS: We prepared a dual-network hydrogel (DN gel) based on FDA-approved PRP and sodium alginate (SA) through a simple "one-step" activation process. In vivo study, adipose tissue with saline (control group), SA gel (SA gel group), PRP gel (PRP gel group), and DN gel (DN gel group) was injected subcutaneously into the dorsum of nude mice. At 4 and 12 weeks after injection, tissues were assessed for volume and weight. Hematoxylin and eosin staining (HE) and immunofluorescence staining were performed for histological assessment. RESULTS: DN gel exhibits long-lasting growth factor effects, surpassing conventional clinical PRP gel regarding vascularization potential. In fat transplantation experiments, DN gel demonstrated improved vascularization of transplanted fat and increased retention rates, showing promise for clinical applications. CONCLUSIONS: DN gel-assisted lipofilling can significantly improve the retention rate and quality of transplanted fat. DN gel-assisted lipofilling, which is considered convenient, is a promising technique to improve neovascularization and fat survival. 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.

Particles of Different Sizes Affect the Retention Pattern of the Fat Grafts in a Mouse Model.

BACKGROUND: Autologous fat grafting is an effective form of soft tissue regeneration. However, the optimal fat particle size and graft retention pattern need more research. METHODS: The mouse inguinal fat pad was harvested and cut into fat particles of different diameters: ≥ 5 mm, 3-4 mm, 2-3 mm, 1-2 mm and 1 mm (micro-fat). A volume of 0.2 ml fat was transplanted into another mouse dorsum. Volume and retention rate were measured at 1, 4, 8 and 12 weeks. Histology analysis was performed. Immunofluorescence staining was used to evaluate M1 and M2 macrophage infiltration and graft angiogenesis. RESULTS: Fat retention was highest in the "> 5 mm" group and lowest in the "micro-fat" group. Large vacuoles were more common in larger-diametered fat particles. There was less collagen accumulation in the well-vascularized connective tissue in the "1-2 mm" group. The infiltrated nucleated cells peak at week 4 in groups of fat particles under 3 mm and at week 8 in in groups with fat particles above 3 mm. The number of M1 macrophages peaked at week 1 and then declined in all groups except for the "5 mm" group. The number of M2 macrophages peaked at week 4 and gradually decreased through 12 weeks in the groups below 3 mm, but increased through 12 weeks in the groups above 3 mm. Vascular intensity was similar to M2 macrophage prevalence. CONCLUSIONS: Fat particles of different sizes may posses different retention patterns. Larger grafts have higher retention rate but worse quality. Meanwhile, smaller grafts have better quality with lower retention rate. 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 .

Effects of Melatonin on Fat Graft Retention Through Browning of Adipose Tissue and Alternative Macrophage Polarization.

BACKGROUND: Melatonin is a widely used drug that can affect adipocyte inflammation, resulting in adipose tissue browning. Inducing the browning of white fat and changing the inflammatory microenvironment of early transplanted fat have positive effects on the retention rate of fat grafts. This study aimed to evaluate the effects of melatonin on fat graft retention, determine whether it is related to adipose tissue browning and the inflammatory microenvironment, and explore the underlying mechanisms. METHODS: A C57BL/6 mice fat transplantation model was established. The mice were divided into a control group (ethanol), a high-dose group (40 mg/kg/day melatonin), a medium-dose group (20 mg/kg/day melatonin), and a low-dose group (10 mg/kg/day melatonin). They were also given oral gavage treatment for 2 weeks. The grafted fat was collected 2, 4, and 12 weeks after treatment. RESULTS: The medium-dose and high-dose melatonin groups had significantly higher fat graft retention rates than the control group at 12 weeks. The medium-dose melatonin group had smaller multilocular adipocytes, which enhanced the expression of uncoupling protein 1 and increased neovascularization in the grafted fat. The medium-dose group also had a higher distribution of M2 macrophages. CONCLUSIONS: These findings suggest that melatonin administration can improve the retention of fat grafts through polarization of macrophages toward the anti-inflammatory type and induction of adipose tissue browning. 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 .

Meta-Analysis of the Oncological Safety of Autologous Fat Grafting After Breast Cancer on Basic Science and Clinical Studies.

BACKGROUND: The purpose of the present study was to comprehensively evaluate the oncological safety of autologous fat grafting after breast cancer by combining experimental and clinical studies. METHODS: All studies published before August 2021 were collected by searching PubMed, Cochrane, Embase, Web of Science, SINOMED, and China National Knowledge Infrastructure. After screening the research and extracting the data, RevMan was used to perform the meta-analysis. RESULTS: Five basic science studies and 26 clinical studies, involving a total of 10,125 patients, were eventually included. In the basic science studies, adipose-derived stem cells promoted breast cancer growth, but fat grafting and adipose-derived stem cells plus fat grafting were not associated with breast cancer growth. An overall analysis of clinical studies showed that autologous fat grafting does not increase the risk of breast cancer recurrence. Subgroup analyses indicated that autologous fat grafting did not increase the risk of breast cancer recurrence in Asian or Caucasian patients, in patients undergoing breast-conserving surgery or modified radical mastectomy, in patients with in situ carcinomas or invasive carcinomas, or in patients undergoing postoperative radiotherapy. CONCLUSION: This study combined experimental and clinical studies to conclude that autologous fat grafting does not increase the risk of breast cancer recurrence. However, the experimental results suggest that adipose-derived stem cells should be used with caution after breast cancer surgery. LEVEL OF EVIDENCE III: 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 .

Severe Vascular Complications Caused by Facial Autologous Fat Grafting: A Critical Review.

BACKGROUND: Vascular embolism is the most severe complication after autologous fat grafting. With a worldwide increase in fat grafting, there has been a rise in severe vascular complications, such as ophthalmic artery embolism, cerebral artery embolism, and even death. This article aims to review the role of fat in causing severe vascular complications and the association between fat grafting and severe vascular complications. METHODS: A critical review was conducted by appraising the cases of severe vascular complications associated with facial fat grafting reported globally. Repeated cases that were reported in multiple publications were further screened. RESULTS: The final search yielded 50 publications in English that met the inclusion criteria for review. A total of 113 cases of fat-induced severe vascular complications in the literature were identified. The number of cases reported yearly has increased over time, with even more significant increases since 2010. The glabella and temple are the most common sites of severe vascular complications described in the literature. In addition, only one case of ophthalmic artery embolism and one case of cerebral artery embolism have been treated successfully. CONCLUSIONS: Given the increase in reported cases of severe vascular complications, both doctors and patients should pay careful attention to the risks of facial fat grafting. Because of the unclear mechanism of vascular embolism and the lack of guidelines for prevention and treatment, the effective cure rate is unsatisfactory. We propose that preventing vascular embolism is a priority in fat grafting and that timely, multidisciplinary treatment should be performed when severe vascular complications occur. It is necessary in future studies to explore the mechanisms of vascular embolism and effective treatment strategies to promote the development of fat grafting.

Ureteral anastomosis with a polyimide stent in rat kidney transplantation.

Background: Complications associated with ureteral anastomosis in kidney transplantation are highly prevalent, despite the development of various types of stents. The current stent materials and placement methods have several limitations. This study attempts to provide an alternative by investigating ureteral anastomosis with a polyimide stent and a modified placement method in a rat model of kidney transplantation.Methods: Sprague-Dawley rats were randomly divided into Group I: sham operation, Group II: autologous ureteral anastomosis, and Group III: isogenic kidney transplantation with ureteral anastomosis. For the anastomosis, a polyimide stent with a previously placed 11-0 silk was inserted into the ureter. The stent and ureter were fixed with 11-0 silk sutures. The kidney weight and serum creatinine were recorded. The ureteral and renal sections were taken for histological analysis.Results: None of the stents had migrated. Urethral patency was achieved. Further, there were no evident histological changes in the anastomosed ureters. The serum creatinine level in group III was significantly higher than the other two groups, but there was no significant difference in kidney weight among the groups at postoperative week 12. Finally, the histological structure of kidneys in groups II and III only showed minor changes.Conclusions: The current anastomosis method with polyimide stent causes minimal damage to the ureteral walls and minimizes the possibility of stent migration. Therefore, this method of ureteral anastomosis with the polyimide stent should be explored for its potential benefits in more animal kidney transplantation models, thus providing an alternative for the clinical setting.

Conventional Nanofat and SVF/ADSC-Concentrated Nanofat: A Comparative Study on Improving Photoaging of Nude Mice Skin.

BACKGROUND: Nanofats could improve photoaging. Stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) may play pivotal roles. However, SVFs and ADSCs in nanofats processed by conventional methods cannot be enriched. Some researchers have found that after centrifugation, the SVF/ADSC density increases from top to bottom. OBJECTIVES: The authors hypothesized that centrifugation can be used to obtain SVF/ADSC-concentrated nanofats that are superior to conventional nanofats in improving the photoaging of skin. METHODS: After a photoaging model was successfully established in nude mice, the back of each mouse was divided into 4 areas and randomly injected with conventional nanofat, centrifuged nanofat (either the middle or lower layer of centrifuged nanofat), or normal saline. Wrinkles, dermis thickness, dermal collagen content, and elastic fiber morphology were measured and compared at weeks 4 and 8. RESULTS: Compared with the wrinkles in the physiological saline injection areas, the wrinkles in the areas injected with the 3 nanofats (lower and middle layers of centrifuged nanofat and conventional nanofat) were significantly reduced. All 3 nanofat groups showed increased dermal thickness, increased collagen content, and a more regular distribution of elastic fibers compared with the saline injection areas. CONCLUSIONS: The study established the efficacy of nanofats in improving photoaging by reducing wrinkles and increasing the thickness of dermal collagen, making nanofats a promising novel treatment for photoaging. The SVF/ADSC-concentrated nanofats exhibited the most improvement.

Improving the Retention Rate of Fat Grafts in Recipient Areas via Botulinum Toxin A Treatment.

BACKGROUND: Improving the retention rate of transplanted fat is, currently, of great concern. Partial immobilization, angiogenesis, and adipose tissue-derived stem cells, all proven to be influenced by botulinum toxin A (BTX-A), are significant in fat graft retention. OBJECTIVES: The authors sought to determine the impact of BTX-A on fat grafts. METHODS: Our study included 12 Sprague Dawley rats and each rat's hind limbs were randomly designated as the BTX-A side and control side. We injected 0.2 mL of BTX-A-treated fat into the quadriceps femoris and subcutaneous space of the BTX-A sides. This was also done for the control sides but with untreated fat. We performed electroneuromyography of recipient muscles at 1 week post-operation. The rats were euthanized at 12 weeks post-operation and we observed the fat retention rate, the fat's histologic characteristics, and the density of vessels and mature adipocytes. RESULTS: The amplitudes of electroneuromyography were smaller for the BTX-A sides than the control sides. For intramuscularly injected fat, the BTX-A sides had better retention rates and histologic characteristics and a higher density of vessels and mature adipocytes than the control sides. For subcutaneously injected fat, the BTX-A sides had better histologic characteristics and a higher density of vessels and mature adipocytes than the control sides, but the retention rates were not significantly different between the 2 sides. CONCLUSIONS: Injecting BTX-A-treated fat grafts can immobilize the surrounding muscles. BTX-A can improve the density of vessels and mature adipocytes, histologic characteristics of fat grafts, and retention rate of fat grafts transplanted into muscles.

Transfusion of ethylene carbodiimide-fixed donor splenocytes prolongs survival of vascularized skin allografts.

BACKGROUND: Allograft rejection is a major obstacle to the widespread clinical application of vascularized composite allotransplantation. Recent studies revealed a noncytoreductive strategy to protect allografts by the transfusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs). To determine whether this approach offers advantages in protecting skin allografts, we examined the immunological protection of infusing ECDI-SPs with a 30-d administration of rapamycin on the skin allografts of mice. MATERIALS AND METHODS: C57BL/6 recipient mice received BALB/c donor full-thickness skin or vascularized skin transplants at day 0, along with the infusion of donor ECDI-SPs 7 d before and 1 d after allotransplantation and a 30-d course of rapamycin. Recipients received ECDI-untreated splenocytes or C3H allografts as controls. In vitro allostimulatory activity of ECDI-SPs and donor-specific ex vivo hyporesponsiveness were tested. Production of related cytokines (TGF-ß, IL-10, IL-1ß, and TNF-α) and expression of CD4+Foxp3+ regulatory T cells (Tregs) were also examined. RESULTS: Transfusion of ECDI-SPs combined with rapamycin significantly prolonged survival of full-thickness skin (median survival time [MST]: 28 d) and full-thickness skin allografts (MST: 71 d) compared with untreated splenocytes (MSTs: 11 d and 30 d) or C3H allografts (MSTs: 11 d and 38 d). This effect was accompanied by increased production of IL-10 and TGF-ß, decreased production of IL-1ß and TNF-α, and expansion of Tregs in vitro and in vivo. CONCLUSIONS: ECDI-SP infusion combined with short-term rapamycin administration provides a promising approach to prolong the skin allograft survival.

The Role of Platelet Concentrates in Facial Fat Grafting.

Autologous fat grafting is increasingly being used as a method for the repair of facial soft tissue defects and facial rejuvenation, given its low risk of adverse effects and high efficacy. However, the unpredictability of graft retention is a limitation of this procedure. In addition, there is no standard procedure to date for autologous fat grafting. Different methods have been developed to increase the retention of grafted fat. For instance, platelet concentrates have been used to directly deliver bioactive factors to grafted fat. Platelet concentrates also provide incidental therapeutic benefits by enhancing the persistence of fat grafted in the face via the release of growth factors and cytokines. In this review, we describe current strategies for improving the survival of facial fat grafts, mainly focusing on the application of growth factors/cytokines and platelet concentrates to fat grafting.

Improvement in the Retention Rate of Transplanted Fat in Muscle by Denervation.

BACKGROUND: Improvement in the retention rate of transplanted fat is currently a topic of interest. The retention of transplanted fat relies heavily on the reestablishment of blood supply and the function of the adipose-derived stem cells (ADSCs), which may both be impeded by mechanical force. However, the effect of mechanical force on the retention of adipose implants remains unclear. OBJECTIVES: This study aimed to evaluate the effectiveness of immobilization on fat retention rate. METHODS: Immobilization was carried out by denervation of the hind limb of rats to reduce the mechanical force. Sprague-Dawley (SD) rats were used, and the two hind limbs were assigned at random to the immobilization side and the control side. On average, 0.4 mL of fat was injected into the bilateral muscle and subcutaneous space of the hind limb, and 6 rats were sacrificed at each time point. The outcome measures included the retention rate, the histologic evaluation, and the density of new vessels and proliferative ADSCs. RESULTS: For the muscle fat, the retention rate improved, and more proliferative ADSCs and new vessels were found in the immobilization group. The histologic evaluation between the two sides was of no statistical significance. For the fat in the subcutaneous space, no statistical difference was observed in all the outcome measures between the two sides. CONCLUSIONS: Regional immobilization of the recipient site by denervation can improve the retention of the fat graft in muscles owing to improved density of the new vessels and proliferative ADSCs.

Heat-Shock Protein 70 Overexpression in Adipose-Derived Stem Cells Enhances Fat Graft Survival.

BACKGROUND: Autologous fat grafting is a prevalent technique used for soft-tissue augmentation; however, the poor survival rate of the grafted tissue remains a drawback of this method. Although adipose-derived stem cells (ASCs) are an attractive candidate for enhancing graft retention, the poor posttransplantation viability of these cells limits their application. Here we investigated whether overexpression of the antiapoptotic protein heat-shock protein 70 (Hsp70) could enhance ASCs' therapeutic potential for fat transplant survival. METHODS: Recombinant adenoviral vectors were used to overexpress Hsp70 in ASCs isolated from a healthy woman. The Hsp70 expression was assessed by quantitative real-time polymerase chain reaction and Western blot analyses. The adipose tissue granules aspirated from another woman were mixed with ASCs expressing green fluorescent protein (GFP)-tagged Hsp70 (group A) or GFP alone (group B), untreated ASCs (group C), and phosphate-buffered saline (group D). Fat mixtures were then injected subcutaneously into the backs of nude mice, and graft survival was compared after 3 months. RESULTS: Adipose-derived stem cells transduced with recombinant adenoviral vectors exhibited significantly increased Hsp70 expression in vitro. Meanwhile, weight retention analyses demonstrated that fat grafts using the group A cell population exhibited significantly higher survival rates than the other treatment groups in vivo. Moreover, histological analyses revealed that fat grafts containing GFP-Hsp70-expressing ASCs yielded significantly lower levels of tissue fibrosis and fat cysts/vacuoles, higher capillary densities, and increased numbers of viable adipocytes than the control groups. CONCLUSIONS: Our data indicate that Hsp70 overexpression enhances the efficacy of ASC therapy by improving the survival and quality of the transplanted fat tissues.

Reconstruction of Large Postburn Facial-Scalp Scars by Expanded Pedicled Deltopectoral Flap and Random Scalp Flap: Technique Improvements to Enlarge the Reconstructive Territory.

The scars of face and scalp caused by burning often show as 1 large facial-scalp scar. The deltopectoral flap was recognized as one of the first choices for the facial scar reconstruction. However, this flap cannot cross the level of zygomatic arch traditionally when it was transferred with pedicle. When the flap reconstructed the facial-scalp scars with expanded random scalp flap, another flap was often needed to reconstruct the remaining temple and forehead scars. The authors reviewed 24 patients of large facial-scalp scars reconstructed by expanded pedicled deltopectoral flap and scalp flap with several technique improvements. The seaming scar between the deltopectoral flap and scalp flap in the temple region formed the new hairline. The technique improvements included ligation of the perforating branches of the transverse cervical artery and thoracoacromial artery when dissecting the pocket, the partial bolster compressive dressing to the distal part of the flap and dividing the pedicle partly as a delaying procedure before dividing the pedicle completely. Good skin compliance, normal contours, and emotional expression were noted. There were complications including expander exposure in 3 patients, stretch marks in 5 patients, flap tip necrosis in 2 patients, and mild postoperative hypertrophic scars in 3 patients. In conclusion, the expanded pedicled deltopectoral flap can enlarge the reconstructive territory in face successfully with the technique improvements. The combination of the expanded pedicled deltopectoral flap and scalp flap is a reliable and excellent reconstructive option for large postburn facial-scalp scars.

Transconjunctival Orbital Septum Fat Release and Preservation for Orbitopalpebral Sulcus in Lower Eyelid Blepharoplasty.

BACKGROUND: Compared to the traditional transcutaneous approach, a safe and effective lower eyelid blepharoplasty has been recognized. In 2007, Sadove first reported a series of patients treated with transconjunctival septal suturing, but the inferior orbitopalpebral sulcus was not totally improved. PURPOSE: Orbital septal fat release and preservation through the transconjunctival approach was used to treat 20 young patients with bulging bags and inferior orbitopalpebral sulcus. METHOD: The orbital septal fat was released and transferred to infraorbital rim to be a base for the inferior orbitopalpebral sulcus. RESULT: Obvious bulging fat was released, and the orbitopalpebral sulcus was flattened by released and excessive orbital septal fat. Satisfactory results were achieved. CONCLUSION: The results achieved from this series of patients indicate that orbital septal fat release and preservation through the transconjunctival approach for reducing the orbitopalpebral sulcus is a safe and effective treatment for bulging fat and orbitopalpebral sulcus in young patients. 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 .

Exploring the Possibility of a Retrograde Embolism Pathway from the Facial Artery to the Ophthalmic Artery System In Vivo.

BACKGROUND: Blindness caused by soft tissue fillers is an extremely low-probability event, but it results in great concern because of its devastating consequences. Currently, the mechanism of an embolism is usually considered to be an accidental injection of fillers into the blood vessels of the face, such as a facial artery, and then retrograding into the ophthalmic artery system, which causes retinal ischemic necrosis. In addition, previous studies have shown that there are anastomoses between facial arteries and branches of the ophthalmic artery in cadavers. An in vivo study, however, has not yet been reported. METHODS: This study was approved by the institutional review board of Xijing Hospital, Fourth Military Medical University. Under general anesthesia, we dissected the same side of the face and eyeball in rabbits to manifest the facial artery and retina separately. Later, a needle (27 g) connected to a syringe (10 ml) full of methylene blue was inserted into a rabbit facial artery. Then, after poking a tiny hole in the central retinal artery, methylene blue was injected into the facial artery as quickly as possible (0.5 ml per second). At the same time, we carefully observed whether the central retinal artery had dye spillover or staining in the sclera. If blue dye was observed in the eye ground and/or the sclera, then it was thought to have entered the ophthalmic artery system (a positive result). In contrast, if none of the blue dye was observed, it was considered a negative result. A Chi-square (χ 2) test with a fourfold table was used to compare the differences in the frequencies of blue dye observed between living and dead rabbits. A value of p < 0.05 was considered significant. RESULTS: One of the 20 rabbits showed the appearance of blue dye in the ophthalmic artery system in vivo, and the remaining 19 living rabbits had negative results. All 20 of the dead rabbits showed dye appearance in the eye ground. A statistically significant difference existed between the living and dead rabbits (p < 0.05). CONCLUSION: In vivo, fillers can retrogradely enter the ophthalmic artery if the fillers entered the facial artery. Although the possibility is much lower in vivo than it is in corpses, adequate attention should be paid because of the catastrophic complications. LEVEL OF EVIDENCE V: 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 .

Reversible Alopecia with Localized Scalp Necrosis After Accidental Embolization of the Parietal Artery with Hyaluronic Acid.

Hyaluronic acid (HA) filler injection is widely used for soft-tissue augmentation. Complications associated with HA filling are not uncommon; however, HA-induced alopecia is a rarely reported complication that could result in severe secondary psychological trauma. The etiology, clinical traits, treatment strategies, outcomes, and possible reversibility of HA-induced alopecia have not been characterized. Here, we report a case in which bilateral temple injections of 6.5 mL of HA led to persistent pain over the left scalp for several days. Although the pain was relieved at day 9 after 600 U of hyaluronidase were injected in the left temple, the patient developed localized alopecia at the left temporoparietal region with central skin necrosis at day 15. After topical applications of recombinant bovine basic fibroblast growth factor gel and 2% minoxidil spay, the necrotic skin wound was healed at day 42. Hair regrowth and normal hair density were restored at day 74. Analyses of Doppler ultrasound examinations and histopathology of the skin biopsy suggested that mild ischemia of the left temporoparietal region led to reversible alopecia, while the permanent hair loss in the left parietal area was associated with severe skin ischemia. Therefore, the key to treatment would be to focus on the effective correction of severe ischemia-induced skin necrosis to prevent permanent hair loss. Level of Evidence V 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 .

Computed Tomographic Angiography-Based Characterization of Source Blood Vessels for Nipple-Areola Complex Perfusion in Hypertrophic Breasts.

BACKGROUND: Current knowledge about the blood supply of the nipple-areola complex (NAC) has largely been derived from studies on cadavers or persons with breasts of normal size. The aim of this study was to identify and classify the NAC blood supply by computed tomographic angiography (CTA) examination in female volunteers with breast hypertrophy. METHODS: CTA examination was performed on hypertrophic breasts of 23 female subjects. The main blood supplies were revealed through image data analyses. The dominant blood supply of the NAC and its vascular sources were identified and sorted. The detectable diameter threshold of blood vessels was set beyond 1.0 mm. RESULTS: A total of 61 dominant blood vessels were identified. The source arteries were traced as the internal thoracic artery (ITA, 50.8%), lateral thoracic artery (LTA, 27.8%), thoracoacromial artery (TA, 14.8%), brachial artery (BA, 3.3%), and axillary artery (AA, 3.3%), and the corresponding reproducibility of these source vessels was 31, 37, 9, 4.3, and 4.3%, in all breasts. The intercostal artery (IA) was not identified as a dominant NAC supplying vessel in any CTA scan image. Twenty-six breasts had only one dominant artery, whereas 17 breasts showed multiple dominant blood supplies. Three breasts showed no dominant blood vessels of the NAC, with diameters greater than the detectable threshold of 1.0 mm, and 52.2% of the breasts demonstrated anatomically symmetrical patterns of blood supply for the NAC. CONCLUSIONS: The ITA, LTA, and TA are likely to be the main vessel sources, whereas the IA is unlikely to be the dominant vessel for NAC perfusion, on the basis of the studied breasts. An asymmetrical pattern of bilateral breast blood supply was demonstrated in a considerable portion of the females with breast hypertrophy in this study. 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 .

Emerging strategies for tissue engineering in vascularized composite allotransplantation: A review.

Vascularized composite allotransplantation (VCA), which can effectively improve quality of life, is a promising therapy for repair and reconstruction after face or body trauma. However, intractable issues are associated with VCA, such as the inevitable multiple immunogenicities of different tissues that cause severe rejection, the limited protocols available for clinical application, and the shortage of donor sources. The existing regimens used to extend the survival of patients receiving VCAs and suppress rejection are generally the lifelong application of immunosuppressive drugs, which have side effects. Consequently, studies aiming at tissue engineering methods for VCA have become a topic. In this review, we summarize the emerging therapeutic strategies for tissue engineering aimed to prolong the survival time of VCA grafts, delay the rejection and promote prevascularization and tissue regeneration to provide new ideas for future research on VCA treatment.