Combination Administration of Heparin and Nitroglycerin for the Treatment of Polycaprolactone-Induced Intravascular Embolism: A Preclinical Investigation.

BACKGROUND: As a new-generation collagen stimulator, polycaprolactone (PCL) containing filler has been extensively applied in facial dermal fillers and other medical aesthetic fields. However, inadvertent intravascular injection of PCL may result in complications such as tissue edema, flap necrosis, and even blindness. To date, there is no effective treatment for PCL-induced intravascular embolism. OBJECTIVES: The aim of this study was to identify a viable resolution for the embolism resulting from intravascular administration of PCL-containing fillers. METHODS: Two different animal experiments were performed: (1) PCL-induced rat inferior epigastric arteries embolism, followed by gross observation, histological evaluation, and cytokines analysis from serum; and (2) PCL-induced rabbit auricular artery embolism, immediately treated with heparin and nitroglycerin. The ears were then evaluated by gross observation, Laser speckle imaging, in vivo imaging system (IVIS) imaging, and histological evaluation. Saline and hyaluronic acids (HA) were used as controls, hyaluronidase was used as a positive drug. RESULTS: In a rat model of inferior epigastric arteries embolism, both intravascular injection of HA and PCL resulted in flap necrosis, indicating that the filler-induced intravascular embolism can lead to serious complications. In a rabbit model of auricular artery embolism, the combination treatment of heparin and nitroglycerin resulted in a relative blood reperfusion recovery of 80% in the ischemic area of the PCL group on day 7 post-operation, which was comparable to that of the HA group treated with hyaluronidase. Histological analysis revealed that the administration of heparin and nitroglycerin significantly attenuated intravascular thrombosis formation and inflammatory cell aggregation. CONCLUSIONS: The combination of heparin and nitroglycerin effectively restores blood flow reperfusion in the intravascular embolization caused by PCL filler injection, alleviates local tissue edema and flap necrosis. These findings offer a novel approach for future clinical management of intravascular embolization with PCL-containing filler injection. 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 .

A Cross-Sectional Survey on Pain Management in Dermal Filler Injections from Physicians' and Patients' Perspectives.

BACKGROUND: Hyaluronic acid (HA) dermal fillers injection is a common procedure in patients with cosmetic needs. Concomitant pain is a major complaint among patients undergoing HA filler injections. Relevant research is limited and there is no consensus on pain management of dermal filler injection. OBJECTIVES: To assist physicians in determining a more appropriate treatment approach, and to better provide treatment suggestions. METHODS: A nationwide (China) cross-sectional survey was conducted using questionnaires designed for physicians and patients, respectively. A total of 62 semi-structured questionnaires were administered to aesthetic physicians via face-to-face interview, whereas 123 online-based questionnaires were collected from patients who have ever undergone HA treatment. The collected questionnaire information was analyzed using descriptive statistics and content analysis. RESULTS: 42 (67.74%) physicians observed that over 50% of their patients were concerned about pain during injection. 101 (82.11%) of patients were concerned about impending pain ≥5 points (a total score is 10) before injection. For preferred pain relief modalities, 48 (77.42%) physicians would choose a hyaluronic acid dermal filler with lidocaine, and 82 (66.67%) patients would choose anesthetic-containing products. 59 (95.16%) physicians who injected lidocaine-containing hyaluronic acid found patients had a comfortable treatment experience. CONCLUSIONS: Pain management during hyaluronic acid dermal fillers injection is important from both perspectives of physicians and patients. This survey showed that compared with other analgesic methods, lidocaine-containing hyaluronic acid has offered a more satisfying experience. It also provides insights to physicians and patients in pain management. 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 Table of Contents or the online Instructions to Authors www.springer.com/00266 .

" " Codes: A Hyaluronic Acid Injection Procedure of Facial Aesthetics and Rejuvenation for Chinese Patients.

ABSTRACT: We have summarized a simple and effective method of filler injection for facial rejuvenation in Chinese patients and named it " " Codes. It is simple and easy to operate, which worth clinical promotion and application.

Infection caused by Lawsonella clevelandensis after breast augmentation with autologous fat grafting: a case report.

BACKGROUND: Lawsonella clevelandensis is one recently documented anaerobic, which is partially acid-fast. Nevertheless, it is rarely found to be associated with human infections, especially in scope of plastic and cosmetic surgery before our patient who was performed breast augmentation with autologous fat grafting. Breast augmentation is becoming popular, the most common post-surgery complication of which is bacterial infection. CASE PRESENTATION: A 29-year-old female who was found swelling in her right breast and fever after breast augmentation surgery with autologous fat grafting was administered. Before administration, she had been treated with antibiotics (details unknown) for more than 1 month without any significant improvements. After administration, she was treated with intravenous antibiotic empirically and repeated debridement via Vaccuum Sealing Drainage (VSD). And samples of the necrotic tissues and pus collected in surgery were sent for microbiological testing. However, routine examination failed. Thus samples were further collected and sent to Genoxor Medical & Science Technology Inc. (Shanghai, China) to conduct Next-Generation Sequencing (NGS). Surprisingly Lawsonella clevelandensis was determined. Accordingly, sensitive antibiotic was applied in concert with thorough debridement and drainage and finally her condition was completely reversed with wound closure gradually. CONCLUSION: Complications of breast augmentation with autologous fat graft are various, of which infection is most common. Rare pathogen such as Lawsonella clevelandensis infection in human is rare in clinical practice. Moreover, it is difficult to differentiate from non-tuberculous mycobacterium for its partial acid resistance, difficulty to culture and abscess formation. How to determine diagnosis of Lawsonella clevelandensis infection accurately come to be critical In our report, NGS is recommended as a useful method to identify the pathogen, which may provide us a novel tool for refractory wound.

Role of c-Jun N-terminal kinase in the osteogenic and adipogenic differentiation of human adipose-derived mesenchymal stem cells.

Although previous studies have characterized the osteogenic potential of adipose-derived mesenchymal stem cells (AMSCs) in vitro and in vivo, the molecular mechanism involved remains to be fully determined. Previously, we demonstrated that the ERK pathway plays an important role in osteogenesis and regulation of the balance between osteogenesis and adipogenesis. Here, we explored the possible role of JNKs in osteogenesis and adipogenesis of AMSCs. JNK activation in osteo-induced AMSCs was initiated at 15 min, peaked at 30 min, and declined from 45 min to basal levels. Inhibition of the JNK signaling pathway using SP600125 blocked osteogenic differentiation in a dose-dependent manner, which was revealed by an ALP activity assay, extracellular calcium deposition detection, and expression of osteogenesis-relative genes (Runx2, ALP, and OCN) via RT-PCR and real-time PCR. However, blockage of JNK did not induce a switch between osteogenesis and adipogenesis of AMSCs in the presence of dexamethasone, which is different from that of blockage of ERK. Significantly, the blockage of JNK activation in adipo-induced AMSCs by SP600125 stimulated adipogenic differentiation, which was confirmed by Oil Red O staining to detect intracellular lipid droplets, and RT-PCR and real-time PCR analysis for expression of adipogenesis-relative genes (PPARγ2 and aP2). This study suggested a potential function of the JNK pathway in committing osteogenic and adipogenic differentiation of AMSCs in vitro. However, blockage of the JNK pathway is not sufficient to induce a switch from osteogenesis to adipogenesis of AMSCs.

Effects of human adipose-derived stem cells on the viability of rabbit random pattern flaps.

BACKGROUND AIMS: Flap necrosis is the most commonly encountered outcome influencing the effect of operations in clinical practice. The advent of cytotherapy and regenerative medicine with stem cells, especially adipose-derived stem cell therapy, appears to be a promising approach in providing multi-lineage differentiating cells. However, autologous stem cells are limited in both quantity and quality in aging individuals. Hence, xenogenic stem cell therapy was used in this study. METHODS: Random pattern flaps (6 cm × 2 cm) were prepared in a rabbit model transplanted either with 4 × 10(5) human adipose-derived stem cells at five sites or equal volumes of Dulbecco's modified Eagle's medium. At 7 days after operation, the viability of the flaps from both groups was evaluated. We determined the numbers of locally infiltrating T cells, whereas the CD4/CD8 ratio, interferon, interleukin (IL)-2, IL-4 and IL-10 in the serum were determined to evaluate the immunological response of the rabbit. Moreover, Dil labeling was administrated to trace the homing of the transplanted stem cells. RESULTS: Both the survival areas and the capillary number of the flaps that were injected with human adipose-derived stem cells significantly increased as compared with the control group (P < 0.05). Additionally, no significant difference in the immune response was detected between the groups. Dil-labeled stem cells were found to participate in the formation of tubular structures, which were further shown to be CD31+, although not predominantly. CONCLUSIONS: Human adipose-derived stem cells could be used therapeutically to improve the viability of random pattern flaps without detection of serious immune rejection of stem cells.

Proteomic analysis profile of engineered articular cartilage with chondrogenic differentiated adipose tissue-derived stem cells loaded polyglycolic acid mesh for weight-bearing area defect repair.

The present study was designed to investigate the possibility of full-thickness defects repair in porcine articular cartilage (AC) weight-bearing area using chondrogenic differentiated autologous adipose-derived stem cells (ASCs) with a follow-up of 3 and 6 months, which is successive to our previous study on nonweight-bearing area. The isolated ASCs were seeded onto the phosphoglycerate/polylactic acid (PGA/PLA) with chondrogenic induction in vitro for 2 weeks as the experimental group prior to implantation in porcine AC defects (8 mm in diameter, deep to subchondral bone), with PGA/PLA only as control. With follow-up time being 3 and 6 months, both neo-cartilages of postimplantation integrated well with the neighboring normal cartilage and subchondral bone histologically in experimental group, whereas only fibrous tissue in control group. Immunohistochemical and toluidine blue staining confirmed similar distribution of COL II and glycosaminoglycan in the regenerated cartilage to the native one. A vivid remolding process with repair time was also witnessed in the neo-cartilage as the compressive modulus significantly increased from 70% of the normal cartilage at 3 months to nearly 90% at 6 months, which is similar to our former research. Nevertheless, differences of the regenerated cartilages still could be detected from the native one. Meanwhile, the exact mechanism involved in chondrogenic differentiation from ASCs seeded on PGA/PLA is still unknown. Therefore, proteome is resorted leading to 43 proteins differentially identified from 20 chosen two-dimensional spots, which do help us further our research on some committed factors. In conclusion, the comparison via proteome provided a thorough understanding of mechanisms implicating ASC differentiation toward chondrocytes, which is further substantiated by the present study as a perfect supplement to the former one in nonweight-bearing area.

Repair of an articular cartilage defect using adipose-derived stem cells loaded on a polyelectrolyte complex scaffold based on poly(l-glutamic acid) and chitosan.

As a synthetic polypeptide water-soluble poly(l-glutamic acid) (PLGA) was designed to fabricate scaffolds for cartilage tissue engineering. Chitosan (CHI) has been employed as a physical cross-linking component in the construction of scaffolds. PLGA/CHI scaffolds act as sponges with a swelling ratio of 760±45% (mass%), showing promising biocompatibility and biodegradation. Autologous adipose-derived stem cells (ASCs) were expanded and seeded on PLGA/CHI scaffolds, ASC/scaffold constructs were then subjected to chondrogenic induction in vitro for 2weeks. The results showed that PLGA/CHI scaffolds could effectively support ASC adherence, proliferation and chondrogenic differentiation. The ASCs/scaffold constructs were then transplanted to repair full thickness articular cartilage defects (4mm in diameter, to the depth of subchondral bone) created in rabbit femur trochlea. Histological observations found that articular defects were covered with newly formed cartilage 6weeks post-implantation. After 12weeks the regenerated cartilage had integrated well with the surrounding native cartilage and subchondral bone. Toluidine blue and immunohistochemical staining confirmed similar accumulation of glycosaminoglycans and type II collagen in engineered cartilage as in native cartilage 12weeks post-implantation. The result was further supported by quantitative analysis of extracellular matrix deposition. The compressive modulus of the engineered cartilage increased significantly from 30% of that of normal cartilage at 6weeks to 83% at 12weeks. Cyto-nanoindentation also showed analogous biomechanical behavior of the engineered cartilage to that of native cartilage. The results of the present study thus demonstrate the potentiality of PLGA/CHI scaffolds in cartilage tissue engineering.

The stimulation of osteogenic differentiation of human adipose-derived stem cells by ionic products from akermanite dissolution via activation of the ERK pathway.

Our previous study indicates that akermanite, a type of Ca-, Mg-, Si-containing bioceramic, can promote the osteogenic differentiation of hASCs. To elucidate the underlying mechanism, we investigated the effect of the extract from akermanite, on proliferation and osteogenic differentiation of hASCs. The original extract was obtained at 200 mg akermanite/ml LG-DMEM and further diluted with LG-DMEM. The final extracts were denoted as 1/2, 1/4, 1/8, 1/16, and 1/32 extracts based on the concentrations of the original extract. The LDH assay and live/dead stain were used to reveal the cytotoxicity of the different extracts on hASCs, while the DNA assay was carried out to quantitatively evaluate the proliferation of cells after being cultured with the extracts for 1, 3 and 7 days. Flow cytometry for cell cycle analysis was carried out on cells cultured in two media (GM and 1/2 extract) in order to further analyze the effect of the extract on cell proliferation behaviors. Osteogenic differentiation of hASCs cultured in the extracts was detected by ALP expression and calcium deposition, and further confirmed by real-time PCR analysis. It was shown that Ca, Mg and Si ions in the extract could suppress the LDH release and proliferation of hASCs, whereas promote their osteogenic differentiation. Such effects were concentration-dependent with the 1/4 extract (Ca 2.36 mM, Mg 1.11 mM, Si 1.03 mM) being the optimum in promoting the osteogenic differentiation of hASCs. An immediate increase in ERK was observed in cells cultured in the 1/4 extract and such osteogenic differentiation of hASCs promoted by released ions could be blocked by MEK1-specific inhibitor, PD98059. Briefly, Ca, Mg and Si ions extracted from akermanite in the concentrations of 2.36, 1.11, 1.03 mM, respectively, could facilitate the osteogenic differentiation of hASCs via an ERK pathway, and suppress the proliferation of hASCs without significant cytotoxicity.