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BACKGROUND: The prevalence of skin redundancy and lack of creases in the Asian upper eyelids makes blepharoplasty popular. Although many incision designs have been developed to improve upper eyelid laxity, there is a lack of a universal method to match various upper eyelid conditions. We present a systematic preoperative evaluation and design approach that incorporates eye esthetics to determine the shape and amount of skin to be removed to create attractive eyes. METHODS: A retrospective review of 352 patients who underwent incisional blepharoplasty from May 2020 to May 2022 was performed. The excised area was determined preoperatively according to the degree of upper eyelid skin laxity, and the best of the three precise designs is chosen. RESULTS: All patients undergoing the procedure achieved a satisfactory eyelid appearance immediately after surgery. Patients were followed up for 3 to 12 months. All patients had significant improvement in upper eyelid skin laxity and a natural shape of the eyelid. No defects that required revision surgery to improve were present, and 91.7% of the patients were satisfied with the long-term outcome. CONCLUSIONS: This systematic approach to preoperative design is simple, effective, and feasible to avoid scar exposure while addressing the lateral hood and achieve an attractive blepharoplasty appearance.
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The cellular functions, such as tissue-rebuilding ability, can be directly affected by the metabolism of cells. Moreover, the glucose metabolism is one of the most important processes of the metabolism. However, glucose cannot be efficiently converted into energy in cells under ischemia hypoxia conditions. In this study, a high-energy intermediate fructose hydrogel (HIFH) is developed by the dynamic coordination between sulfhydryl-functionalized bovine serum albumin (BSA-SH), the high-energy intermediate in glucose metabolism (fructose-1,6-bisphosphate, FBP), and copper ion (Cu2+ ). This hydrogel system is injectable, self-healing, and biocompatible, which can intracellularly convert energy with high efficacy by regulating the glucose metabolism in situ. Additionally, the HIFH can greatly boost cell antioxidant capacity and increase adenosine triphosphate (ATP) in the ischemia anoxic milieu by roughly 1.3 times, improving cell survival, proliferation and physiological functions in vitro. Furthermore, the ischemic skin tissue model is established in rats. The HIFH can speed up the healing of damaged tissue by promoting angiogenesis, lowering reactive oxygen species (ROS), and eventually expanding the healing area of the damaged tissue by roughly 1.4 times in vivo. Therefore, the HIFH can provide an impressive perspective on efficient in situ cell energy supply of damaged tissue.
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BACKGROUND: The nasal tip plays a crucial role both esthetically and functionally. The application of nasal tip grafts is an effective method for improving nasal tip form. Ear cartilage is a common choice for nasal tip grafts, but it still presents several challenges in clinical application that need to be addressed. This study aims to address the issues associated with the use of ear cartilage in clinical rhinoplasty applications through the development of a novel septal extension graft using ear cartilage for nasal tip reconstruction. METHODS: From May 2018 to April 2022, a total of 132 cases of nasal tip reconstruction surgeries were performed using a seagull-shaped nasal septum extension graft, constructed with bilateral cavum concha cartilage. Among these cases, 25 patients had previously undergone rhinoplasty using silicone implant, 7 patients had undergone augmentation rhinoplasty using expanded polytetrafluoroethylene, whereas the rest were primary rhinoplasty cases. All patients were followed up for a period ranging from 3 months to 4 years postoperatively, with photographs taken to assess the nasal tip morphology. RESULTS: In this study, all patients exhibited good healing of the incisions made at the posterior aspect of the auricular concha, with no occurrences of hematoma and inconspicuous scarring. In 116 cases, significant improvement in nasal appearance and a realistic nasal tip form were achieved postoperatively, yielding satisfactory outcomes. Only 16 patients experienced minor issues with nasal tip morphology, which were subsequently improved through further surgical procedures. CONCLUSION: This study reports a surgical technique for nasal tip refinement using bilaterally harvested cavum concha cartilage to construct a seagull-shaped nasal septal extension graft. The procedure has achieved satisfactory outcomes, and its application is worth extending to clinical practice.
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Exudate management is critical to improve chronic wound healing. Herein, inspired by a Janus-structured lotus leaf with asymmetric wettability, a Janus electrospun short fiber scaffold is fabricated via electrospinning technologies and short fiber modeling. This scaffold is composed of hydrophilic 2D curcumin-loaded electrospun fiber and hydrophobic 3D short fiber via layer-by-layer assembly and electrostatic interactions which can aggregate the wound exudate by pumping from the hydrophobic layer to the hydrophilic via multiple contact points between hydrophilic and hydrophobic fibers, and simultaneously trigger the cascade release of curcumin in the upper 2D electrospun fiber. The 3D short fiber with high porosity and hydrophobicity can quickly aggregate exudate within 30 s after compounding with hydrophilic 2D electrospun fiber via a spontaneous pump. In vitro experiments show that Janus electrospun short fiber has good biocompatibility, and the cascade release of curcumin can significantly promote the proliferation and migration of fibroblasts. In vivo experiments show that it can trigger cascade release of curcumin by aggregating wound exudate, so as to accelerate wound healing process and promote collagen deposition and vascularization. Hence, this unique biometric Janus scaffold provides an alternative for chronic wound healing.
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Curcumina , Nanofibras , Colágeno , Curcumina/farmacología , Fibroblastos , Nanofibras/química , Porosidad , Cicatrización de HeridasRESUMEN
ABSTRACT: Fat repositioning is an effective way to treat tear trough deformity (TTD) in Asians. Recent techniques mainly focused on the fixation technique, whereas how to precisely shape and individually quantify the fat pedicle has been ignored. This article introduced an individualized, targeted, and tension-free technique to fabricate a fan-shaped thin septum fat pedicle for repositioning. Furthermore, a layer-level fixation method was advocated to provide sufficient, continuous, uninterrupted filling of the TTD. From January 1, 2009, to December 31, 2018, 492 patients underwent this procedure. Through a transconjunctival incision, a continuous fan-shaped, tension-free, customized septum fat pedicle was precisely designed to match the TTD anatomy. The pedicle could either be elongated, or thickened, or debulked, or translocated, to meet the patients' individual needs. At the same time, a layer-level fat pedicle fixation technique was applied to fully interrupt the TTD. The mean operation time was 60â±â9.3âminutes. All patients demonstrated a significant improvement with elimination of both eye bags and TTD. High satisfaction was noted among the patients. No obvious resorption of the fat pedicles was observed, and the lower lid contour improvements were durable. One infection occurred after 3âdays of surgery, and was resolved by removal of the suture followed by topical application of iodine and oral antibiotics for 3 to 5âdays. No other complications were observed. Precisely repositioning transconjunctival fat using a layer-level fixation technique with a fan-shaped thin fat pedicle under a subperiosteal plane is an effective, lasting, and safe approach for individually treating TTD.
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Blefaroplastia , Tejido Adiposo/trasplante , Párpados/cirugía , Humanos , SuturasRESUMEN
Reducing carbon emission intensity is crucial for achieving sustainable development. Carbon emission intensity is expressively affected by the issuance of green bonds. Thus, it is imperative to assess the influence of green bond issuance on carbon emissions and examine their correlation. Such research holds great potential to expedite the overhaul and modernization of businesses and to construct a circular economy system. This paper uses the spatial Durbin model to draw empirical conclusions by using data from 26 provinces in China between 2016 and 2021. Firstly, under different spatial matrices, it has been analyzed that an increase of 1% in the issuance of green bonds leads to a reduction of 0.306% or 0.331% in carbon emission intensity. It shows that green bonds have the potential to substantially reduce carbon intensity. Additionally, the intensity of emissions in the current period is driven by the intensity of emissions in the previous period. Secondly, the analysis of mediated transmission suggests that green bonds can ultimately reduce carbon emission intensity by changing the energy consumption structure or improving the efficiency of green technology innovation. Thirdly, the analysis of heterogeneity shows that the inhibitory effect of green bond issuance on carbon emissions is stronger in less economically developed regions than in economically developed regions. There is a significant inhibitory effect of green bond issuance in neighboring provinces on local carbon emission intensity. This effect is present only in provinces in less economically developed regions and not in economically developed regions.
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Carbono , Carbono/química , Carbono/análisis , China , Desarrollo SostenibleRESUMEN
BACKGROUND: Keloid (KL) is a common benign skin tumor. KL is typically characterized by significant fibrosis and an intensive inflammatory response. Therefore, a comprehensive understanding of the interactions between cellular inflammation and fibrotic cells is essential to elucidate the mechanisms driving the progression of KL and to develop therapeutics. OBJECTIVE: Investigate the transcriptome landscape of inflammation and fibrosis in keloid scars. METHODS: In this paper, we performed transcriptome sequencing and microRNA (miRNA) sequencing on unselected live cells from six human keloid tissues and normal skin tissues to elucidate a comprehensive transcriptome landscape. In addition, we used single-cell RNA sequencing (scRNA-seq) analysis to analyze intercellular communication networks and enrich fibroblast populations in two additional keloid and normal skin samples to study fibroblast diversity. RESULTS: By RNA sequencing and a miRNA-mRNA-PPI network analysis, we identified miR-615-5p and miR-122b-3p as possible miRNAs associated with keloids, as they differed most significantly in keloids. Similarly, COL3A1, COL1A2, THBS2, TNC, IGTA, THBS4, TGFB3 as genes with significant differences in keloid may be associated with keloid development. Using single-cell RNA sequencing data from 24,086 cells collected from normal or keloid, we report reconstructed intercellular signaling network analysis and aggregation to modules associated with specific cell subpopulations at the cellular level for keloid alterations. CONCLUSIONS: Our multitranscriptomic dataset delineates inflammatory and fibro heterogeneity of human keloids, underlining the importance of intercellular crosstalk between inflammatory cells and fibro cells and revealing potential therapeutic targets.
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Queloide , MicroARNs , Humanos , Queloide/genética , Queloide/patología , Transcriptoma , MicroARNs/genética , Perfilación de la Expresión Génica , Fibroblastos/patología , Inflamación/genética , Inflamación/patologíaRESUMEN
BACKGROUND: Adipose tissue-derived stem cell-derived apoptotic bodies (ADSC-ABs) have shown great potential for immunomodulation and regeneration, particularly in diabetic wound therapy. However, their local application has been limited by unclear regulatory mechanisms, rapid clearance, and short tissue retention times. METHODS: We analyzed the key role molecules and regulatory pathways of ADSC-ABs in regulating inflammatory macrophages by mRNA sequencing and microRNA (miRNA) sequencing and then verified them by gene knockdown. To prevent rapid clearance, we employed microfluidics technology to prepare methacrylate-anhydride gelatin (GelMA) microspheres (GMS) for controlled release of ABs. Finally, we evaluated the effectiveness of ADSC-AB-laden GMSs (ABs@GMSs) in a diabetic rat wound model. FINDINGS: Our results demonstrated that ADSC-ABs effectively balanced macrophage inflammatory polarization through the janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, mediated by miR-20a-5p. Furthermore, we showed that AB@GMSs had good biocompatibility, significantly delayed local clearance of ABs, and ameliorated diabetic wound inflammation and promoted vascularization, thus facilitating its healing. CONCLUSIONS: Our study reveals the regulatory mechanism of ADSC-ABs in balancing macrophage inflammatory polarization and highlightsthe importance of delaying their local clearance by GMSs. These findings have important implications for the development of novel therapies for diabetic wound healing. FUNDING: This research was supported by the National Key Research and Development Program of China (2020YFA0908200), National Natural Science Foundation of China (82272263, 82002053, 32000937, and 82202467), Shanghai "Rising Stars of Medical Talents" Youth Development Program (22MC1940300), Shanghai Municipal Health Commission (20204Y0354), and Shanghai Science and Technology Development Funds (22YF1421400).
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Diabetes Mellitus , Vesículas Extracelulares , Ratas , Animales , China , Diabetes Mellitus/metabolismo , Cicatrización de Heridas/genética , Células Madre/metabolismo , Macrófagos/metabolismoRESUMEN
The dynamic balance between hypoxia and oxidative stress constitutes the oxygen-related microenvironment in injured tissues. Due to variability, oxygen homeostasis is usually not a therapeutic target for injured tissues. It is found that when administered intravenously, mesenchymal stem cells (MSCs) and in vitro induced apoptotic vesicles (ApoVs) exhibit similar apoptotic markers in the wound microenvironment where hypoxia and oxidative stress co-existed, but MSCs exhibited better effects in promoting angiogenesis and wound healing. The derivation pathway of ApoVs by inducing hypoxia or oxidative stress in MSCs to simulate oxygen homeostasis in injured tissues is improved. Two types of oxygen-related environmental stressed ApoVs are identified that directly target endothelial cells (ECs) for the accurate regulation of vascularization. Compared to normoxic and hypoxic ones, oxidatively stressed ApoVs (Oxi-ApoVs) showed the strongest tube formation capacity. Different oxygen-stressed ApoVs deliver similar miRNAs, which leads to the broad upregulation of EC phosphokinase activity. Finally, local delivery of Oxi-ApoVs-loaded hydrogel microspheres promotes wound healing. Oxi-ApoV-loaded microspheres achieve controlled ApoV release, targeting ECs by reducing the consumption of inflammatory cells and adapting to the proliferative phase of wound healing. Thus, the biogenerated apoptotic vesicles responding to oxygen-related environmental stress can target ECs to promote vascularization.
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Apoptosis , Células Endoteliales , Estrés Oxidativo , Oxígeno , Animales , Células Endoteliales/metabolismo , Oxígeno/metabolismo , Cicatrización de Heridas/fisiología , Ratones , Humanos , Células Madre Mesenquimatosas/metabolismo , Vesículas Extracelulares/metabolismoRESUMEN
Arterial vasospasm after microsurgery can cause severe obstruction of blood flow manifested as low tissue temperature, leading to tissue necrosis. The timely discovery and synchronized treatment become pivotal. In this study, a reversible, intelligent, responsive thermosensitive hydrogel system is constructed employing both the gel-sol transition and the sol-gel transition. The "reversible thermosensitive (RTS)" hydrogel loaded with verapamil hydrochloride is designed to dynamically and continuously regulate the extravascular microenvironment by inhibiting extracellular calcium influx. After accurate implantation and following in situ gelation, the RTS hydrogel reverses to the sol state causing massive drug release to inhibit vasospasm when the tissue temperature drops to the predetermined transition temperature. Subsequent restoration of the blood supply alleviates further tissue injury. Before the temperature drops, the RTS hydrogel maintains the gel state as a sustained-release reservoir to prevent vasospasm. The inhibition of calcium influx and vasospasm in vitro and in vivo is demonstrated using vascular smooth muscle cells, mice mesenteric arterial rings, and vascular ultrasonic Doppler detection. Subsequent animal experiments demonstrate that RTS hydrogel can promote tissue survival and alleviate tissue injury responding to temperature change. Therefore, this RTS hydrogel holds therapeutic potential for diseases requiring timely detection of temperature change.
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Endothelial cell (EC) injury plays a key role in the chronic wound process. A long-term hypoxic microenvironment hinders the vascularization of ECs, thus delaying wound healing. In this study, CX3CL1-functionalized apoptotic body nanovesicles (nABs) were constructed. The "Find-eat" strategy was implemented through a receptor-ligand combination to target ECs that highly express CX3CR1 in the hypoxic microenvironment, therefore amplifying the "Find-eat" signal and promoting angiogenesis. Apoptotic bodies (ABs) were obtained by chemically inducing apoptosis of adipose-derived stem cells (ADSCs), and then functionalized nABs containing deferoxamine (DFO-nABs) were obtained through a series of steps, including optimized hypotonic treatment, mild ultrasound, drug mixing and extrusion treatment. In vitro experiments showed that nABs had good biocompatibility and an effective "Find-eat" signal via CX3CL1/CX3CR1 to induce ECs in the hypoxic microenvironment, thereby promoting cell proliferation, cell migration, and tube formation. In vivo experiments showed that nABs could promote the rapid closure of wounds, release the "Find-eat" signal to target ECs and realize the sustained release of angiogenic drugs to promote new blood vessel formation in diabetic wounds. These receptor-functionalized nABs, which can target ECs by releasing dual signals and achieve the sustained release of angiogenic drugs, may provide a novel strategy for chronic diabetic wound healing.
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Diabetes Mellitus , Células Endoteliales , Humanos , Preparaciones de Acción Retardada/farmacología , Neovascularización Fisiológica , Neovascularización PatológicaRESUMEN
Organoids are three-dimensional (3D) cell culture systems that simulate the structures and functions of organs, involving applications in disease modeling, drug screening, and cellular developmental biology. The material matrix in organoids can provide a 3D environment for stem cells to differentiate into different cell types and continuously self-renew, thereby realizing the in vitro culture of organs, which has received extensive attention in recent years. However, some challenges still exist in organoids, including low maturity, high heterogeneity, and lack of spatiotemporal regulation. Therefore, in this review, we summarized the culturing protocols and various applications of stem cell-derived organoids and proposed insightful thoughts for engineering stem cells into organoids in view of the current shortcomings, to achieve the further application and clinical translation of stem cells and engineered stem cells in organoid research.
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Induced pluripotent stem cells (iPSCs) that are generated from adult somatic cells are induced to express genes that make them pluripotent through reprogramming techniques. With their unlimited proliferative capacity and multifaceted differentiation potential and circumventing the ethical problems encountered in the application of embryonic stem cells (ESC), iPSCs have a broad application in the fields of cell therapy, drug screening, and disease models and may open up new possibilities for regenerative medicine to treat diseases in the future. In this review, we begin with different reprogramming cell technologies to obtain iPSCs, including biotechnological, chemical, and physical modulation techniques, and present their respective strengths, and limitations, as well as the recent progress of research. Secondly, we review recent research advances in iPSC reprogramming-based regenerative therapies. iPSCs are now widely used to study various clinical diseases of hair follicle defects, myocardial infarction, neurological disorders, liver diseases, and spinal cord injuries. This review focuses on the translational clinical research around iPSCs as well as their potential for growth in the medical field. Finally, we summarize the overall review and look at the potential future of iPSCs in the field of cell therapy as well as tissue regeneration engineering and possible problems. We believe that the advancing iPSC research will help drive long-awaited breakthroughs in cellular therapy.
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Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior. However, capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes. Here, a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation, and the chemical signals provided with chemokine and natural adhesion sites, which guaranteed the precise soft tissue remodeling. This bio-mimicking hydrogel efficiently facilitated cell anchoring, migration, and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors. Besides, the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1α dependent signal pathway. Furthermore, the early polarization of macrophages, collagen deposition and angiogenesis in rat acute wound model, and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve, myocardium, and even bone.
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Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing. How to programmatically activate sequential immune responses is the key for scarless skin regeneration. In this study, an "Inner-Outer" IL-10-loaded electrospun fiber with cascade release behavior was constructed. During the inflammatory phase, the electrospun fiber released a lower concentration of IL-10 within the wound, inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype "M2c" to suppress excessive inflammation response. During the proliferative phase, a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized "M2c" directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration. The "Inner-Outer" IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration, which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.
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The development of science and technology often drew lessons from natural phenomena. Herein, inspired by drying-driven curling of apple peels, hydrogel-based micro-scaled hollow tubules (MHTs) are proposed for biomimicking microvessels, which promote microcirculation and improve the survival of random skin flaps. MHTs with various pipeline structures are fabricated using hydrogel in corresponding shapes, such as Y-branches, anastomosis rings, and triangle loops. Adjustable diameters can be achieved by altering the concentration and cross-linking time of the hydrogel. Based on this rationale, biomimetic microvessels with diameters of 50-500 µm are cultivated in vitro by coculture of MHTs and human umbilical vein endothelial cells. In vivo studies show their excellent performance to promote microcirculation and improve the survival of random skin flaps. In conclusion, the present work proposes and validifies a biomimetic 3D self-forming method for the fabrication of biomimetic vessels and microvascular scaffolds with high biocompatibility and stability based on hydrogel materials, such as gelatin and hyaluronic acid.
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In view of bond rotation flexibility and the additivity of stiff energy, a new equation containing mole fractions of sequences and glass transition temperatures (Tg's) of periodic copolymers was proposed. Meanwhile, the effect of stereochemical sequences was also taken into account. Even for the case of all substitutions on primary (C1), second (C2), and third (C3) carbon atoms adjoining to the given bond (triad sequences effect) to be considered, no intractable parameters exist in the new equation if the periodic copolymers of poly[AB], poly[AAB], and poly[BBA] could be acquired. This may facilitate its convenient application in comparison with the Ham equation (Ham, G. E. J. Macromol. Sci. Chem. 1975, A9, 461), which also concerned triad contributions. The new equation was applied to methyl methacrylate-styrene, ethylene-methyl methacrylate, and ethylene-vinyl acetate copolymers, and excellent fittings were obtained. The parameters obtained may predict Tg values of periodic copolymers that have not been acquired as well as provide useful information on the bond rotation flexibility.