Erratum: Self-Healing and Injectable Hydrogel for Matching Skin Flap Regeneration.

[This corrects the article DOI: 10.1002/advs.201801555.].

Self-Healing and Injectable Hydrogel for Matching Skin Flap Regeneration.

The fabrication of highly biocompatible hydrogels with multiple unique healing abilities for the whole healing process, for example, multifunctional hydrogels with injectable, degradation, antibacterial, antihypoxic, and wound healing-promoting properties that match the dynamic healing process of skin flap regeneration, is currently a research challenge. Here, a multifunctional and dynamic coordinative polyethylene glycol (PEG) hydrogel with mangiferin liposomes (MF-Lip@PEG) is developed for clinical applications through Ag-S coordination of four-arm-PEG-SH and Ag+. Compared to MF-PEG, MF-Lip@PEG exhibits self-healing properties, lower swelling percentages, and a longer endurance period. Moreover, the hydrogel exhibits excellent drug dispersibility and release characteristics for slow and persistent drug delivery. In vitro studies show that the hydrogel is biocompatible and nontoxic to cells, and exerts an outstanding neovascularization-promoting effect. The MF-Lip@PEG also exhibits a strong cytoprotective effect against hypoxia-induced apoptosis through regulation of the Bax/Bcl-2/caspase-3 pathway. In a random skin flap animal model, the MF-Lip@PEG is injectable and convenient to deliver into the skin flap, providing excellent anti-inflammation, anti-infection, and proneovascularization effects and significantly reducing the skin flap necrosis rate. In general, the MF-Lip@PEG possesses outstanding multifunctionality for the dynamic healing process of skin flap regeneration.

Activation of TRPV4 Increases Neovascularization of Rat Prefabricated Flaps.

BACKGROUND: Inadequate neovascularization is a major risk factor that can lead to subsequent necrosis of prefabricated flaps. Recent evidence indicates that transient receptor potential cation channel, subfamily V, member 4 (TRPV4) activates growth and remodeling of collateral arteries in ischemia tissues by responding to elevated fluid shear stress (FSS). Therefore, we evaluated whether TRPV4 could increase neovascularization in prefabricated flaps in a rat model. METHODS: Rat prefabricated skin flaps were created by ligating the right femoral vascular pedicle and implanting it underneath abdominal flaps. Thirty-six male Sprague-Dawley rats were randomly assigned to three groups with different solutions injected subcutaneously in the implantation site around the pedicle: injected with normal saline as the control group; injected with 4α-Phorbol 12,13-didecanoate (4αPDD), a specific TRPV4 activator, as the 4αPDD group; or injected with ruthenium red (RR), a TRPV-blocker, as the RR group. Neovascularization was evaluated by laser speckle contrast imaging (FLPI), histological staining, and enzyme-linked immunosorbent assay (ELISA) within two weeks. Afterwards, the abdominal island flaps were completely elevated and sutured back. The flap viability and survival area were examined on day 7. RESULTS: A larger area of flap survival, higher capillary densities, and higher von Willebrand factor (vWF) expression were observed in the 4αPDD group in comparison to those in the other two groups. The secretion of vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor (bFGF), was significantly elevated in the 4αPDD group. CONCLUSION: Activation of TRPV4 using 4αPDD can significantly increase the survival of prefabricated flaps via neovascularization inducement, possibly through VEGF secretion enhancement. TRPV4 serves as a potential therapeutic neovascularization target in prefabricated flaps.

Discordance of pathological thin melanoma thickness and T stage in SEER registry: impacts on clinical management and research directions.

BACKGROUND: Ultrathin melanoma was previously demonstrated to have higher risk for melanoma-specific mortality using SEER database. However, these guideline-changing conclusions has been recently challenged by miscoding of thickness. This present study was performed to assess the prognosis of thin and ultrathin melanoma using only surgically-treated, pathologically confirmed and after removal of discordant cases. METHODS: Melanoma patients from SEER database who were initially diagnosed with histologically confirmed and surgically treated melanoma from 1998 to 2012 were included. Subjects with discordance between T stage and tumor thickness were excluded. Kaplan-Meier curves, log-rank test and multivariate Cox proportional hazards regression models were used. RESULTS: 55,754 patients met the strict inclusion criteria, but 16 (0.02%) and 803 (1.4%) patients were removed due to T0 stage and discordance between T stage and thickness, respectively. Therefore, 54,935 patients entered the analyses, among which 52,751 were LN negative and 2,184 were LN positive. In either overall or LN-negative patients, a straightforward dose-effect relationship of larger thickness with increasing mortality was observed. In contrast, in LN positive patients, the T1 subgroup demonstrated a similar survival with tumors in T2 mm subgroup. Multivariable analysis revealed same pattern, and significant interaction between T stage and LN involvement was found. Further categorizing T1 melanoma into 10 equal 0.10 mm increments demonstrated an unexpected "N"-shaped pattern of mortality in overall and LN negative ultrathin melanoma but not in LN positive melanoma. CONCLUSIONS: No difference in mortality was observed in T1-3 tumors with LN involvement. External and independent validation studies are warranted.

A murine model of orthotopic periorbital subunit transplantation.

BACKGROUND: Conventional reconstructive methods fail to achieve satisfactory results in total eyelid defect cases. Vascularized composite tissue allotransplantation might provide both good appearance and function for these patients. We developed an orthotopic periorbital transplantation model in rats to facilitate further experimentation in this field. METHODS: In anatomical studies, the vascular distribution to and innervation of the periorbital unit were identified and recorded. Then, according to the anatomical studies, eight orthotopic transplantations and two transplantations with pedicle ligation were performed. The posterior facial vein and the external carotid artery were selected as the graft pedicles, while the temporal and upper zygomatic facial nerves were used for graft innervation. All transplanted eyelids were assessed daily. Micro-CT scanning and hematoxylin and eosin staining of the grafts were performed 60 days after the operation. RESULTS: In total, 90% of recipients tolerated the operation well. All grafts without pedicle ligation survived, and new hair growth was observed. The position of the eyelid was maintained, and eyelid function was partially restored. In the recipients with graft pedicle ligation, the grafts became necrotic and mummified within four to five days. Micro-CT of the surviving grafts showed a good blood supply, and histological staining revealed normal morphology. CONCLUSIONS: A periorbital subunit orthotopic transplantation model was established, which might facilitate future eyelid allotransplantation-related experimentation.

Efficacy and Safety of Cell-Assisted Lipotransfer: A Systematic Review and Meta-Analysis.

BACKGROUND: The main drawback of autologous fat grafting, which is commonly used for soft-tissue augmentation, is the high resorption rate. Cell-assisted lipotransfer has been used to improve fat graft survival; however, evidence for its efficacy and safety is still lacking. METHODS: The authors searched PubMed, Cochrane Library, EBSCO, and EMBASE for clinical studies on cell-assisted lipotransfer published from 2008 through 2014. A meta-analysis was conducted to pool the estimated fat survival rate. Incidence of complications and incidence of multiple operations were calculated. RESULTS: Seventeen articles involving 387 cases were included in the systematic review. The pooled fat survival rate was significantly higher in the cell-assisted lipotransfer group than in the nonlipotransfer group (60 percent versus 45 percent, p = 0.0096). Complication incidence was similar in the two groups. Cell-assisted lipotransfer significantly improved fat survival in the face (by 19 percent) and reduced the incidence of multiple operations (by 13.6 percent). In breast fat grafting, however, fat survival was improved by only 9 percent, which was not statistically significant. Meanwhile, lipotransfer in breast cases was associated with a higher complication incidence compared with face cases (p < 0.001). CONCLUSIONS: This study demonstrates that cell-assisted lipotransfer has better efficacy than conventional fat grafting (non-cell-assisted lipotransfer). It is more applicable to face cases than to breast cases. Until now, there has not been enough evidence of the superiority of cell-assisted lipotransfer over conventional fat grafting for reducing complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Fabrication of New Thermo-pH Responsive Carbon Nanotube Gels.

Stimuli-responsive gels have widespread attraction due to their potential applications. In this work, we have demonstrated the preparation of new multiwall carbon nanotube (MWNT) incorporate multi-responsive (pH and thermal) gels (MWNT-IPN-MRG) though network formation with functional macromolecules that interact each other via hydrogen bonds, covalent networking and temporary associative forces. A simple strategy has been developed to prepare MWNT-IPN-MRG. Typically, surface of MWNTs was facilitated to form network with pH and thermo responsive polymers and converted into smart MWNT-IPN-MRGs. Fourier transform infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy were employed to examine chemical compositions and microstructures of MWNT-IPN-MRGs. The new MWNT-IPN-MRGs showed thermo-pH responsive swelling-deswelling behaviors. The advantageous approach for the preparation of new multiresponsive gel in this study will potentially pave way for the preparation of nanogels for environmental application.