Objective To evaluate knowledge gain associated with an integrated Extracorporeal membrane oxygenation (ECMO) training course combining didactic teaching and simulation, and to explore factors associated with knowledge retention. Methods We conducted a quasi-experimental single-group pretest–posttest study among ECMO-related healthcare providers. Participants completed the same core knowledge test immediately before and after the course, and a subset completed a follow-up re-test via online questionnaire using the same blueprint and scoring standard. Results From April 2020 to December 2024, a total of 165 medical professionals from 43 centers participated in a standardized ECMO training program. The mean pre-test score was 55.2±14.5, which significantly improved to 80.8±11.4 in the post-test (P<0.001). Among the 105 participants who completed follow-up re-testing (63.6%), the median interval between training and re-test was 25 months (range, 4–36). An interval of ≥24 months was independently associated with re-test failure (odds ratio [OR], 14.97; P = 0.020). In contrast, holding a bachelor’s degree (OR, 0.24; P = 0.034) or a master’s degree or higher (OR, 0.06; P = 0.046) was protective. Conclusions An integrated didactic-and-simulation ECMO course was associated with improved knowledge scores, but the study design does not permit attribution of gains specifically to the simulation component. The decline in follow-up re-test performance supports the need for periodic refresher training, particularly beyond 24 months. Controlled comparative studies with skill-based outcomes are needed to isolate the contribution of simulation and to evaluate transfer to practice.

Background:Fulminant myocarditis (FM) in children can progress rapidly to cardiogenic shock, with high risk of mortality. Early recognition of prognostic markers is critical to guide timely escalation of circulatory support. This multicenter study sought to characterize clinical features and identify early predictors of in-hospital mortality in pediatric FM. Methods:We conducted a retrospective cohort study of patients <18 years with FM admitted to eight ECMO-capable pediatric intensive care units between January 2018 and August 2023. Clinical, biochemical, electrocardiographic, and echocardiographic variables were analyzed. Logistic regression was used to identify predictors of mortality, and receiver operating characteristic (ROC) curves were generated to assess discriminatory performance. Results:A total of 187 children were included; 157 (84.0%) required ECMO. In-hospital mortality was 16.6% (31/187). Univariate analysis identified elevated CK-MB, higher peak lactate, and ventricular tachycardia as associated with mortality. In multivariate analysis, peak lactate (AUC 0.791) and CK-MB (AUC 0.774) remained independent predictors. A combined model of peak lactate and ventricular tachycardia demonstrated moderate discrimination (AUC 0.772), whereas a composite model incorporating CK-MB, peak lactate, and ventricular tachycardia achieved the best predictive performance (AUC 0.815). Elevated lactate measured 12 h after initiation of extracorporeal membrane oxygenation or intensive conventional therapy further increased mortality risk (OR 1.219, 95% CI 1.004-1.481). Conclusion:Peak lactate, CK-MB, and ventricular tachycardia are early independent predictors of in-hospital mortality in pediatric FM. Persistent hyperlactatemia within 12 h of advanced support provides additional prognostic value and may assist clinicians in early risk stratification.

Extracorporeal membrane oxygenation (ECMO) has been used to support children with pediatric acute respiratory distress syndrome (PARDS) who fail to respond to conventional management strategies. There is limited literature and guidance on long-term ECMO support for severe PARDS and its impact on lung recovery. We present a case of a 4 month old female who developed severe necrotizing pneumonia following respiratory syncytial virus (RSV) infection. She had subsequent cardiogenic shock and deterioration of lung function, initially requiring venoarterial (VA) ECMO cannulation. She had improvement in cardiac function but developed large pneumatoceles with minimal functional lung tissue, prompting transition to venovenous (VV) ECMO via a right atrial double-lumen cannula and later multisite VV ECMO when she outgrew her previous cannulation. Nitric oxide was added to the sweep gas (sNO) to preserve the membrane oxygenator, extending the life of one oxygenator to over 5 months. The massive bilateral pneumatoceles regressed over time, and the compressed normal lung tissue recovered, allowing her to be weaned off ECMO support and decannulated after 233 days. She underwent tracheostomy decannulation and was discharged home on room air after nearly 10 months in the hospital.

ABSTRACT:Programmed cell death (PCD) plays a central regulatory role in the development and progression of cardiovascular diseases (CVD), and its dysregulated activation or inhibition is closely associated with pathological conditions such as myocardial ischemia and atherosclerosis. In recent years, research on epigenetic regulatory mechanisms has advanced rapidly, with lactylation and m6A methylation emerging as key forms of metabolic epigenetic cross-talk. Lactylation utilizes lactate as a substrate and contributes to energy metabolism reprogramming, inflammatory regulation, and cellular stress adaptation by modulating protein lactylation levels, whereas m6A methylation dynamically regulates posttranscriptional splicing, mRNA stability, and translational efficiency through reversible methylation of RNA molecules. Evidence indicates that these two modifications may exert synergistic or antagonistic effects within PCD signaling networks, thereby jointly influencing the initiation and progression of CVD. This review systematically examines the mechanistic interactions between lactylation and m6A methylation in the multiple forms of PCD, including apoptosis, ferroptosis, and pyroptosis, and their roles in CVD, with particular emphasis on their therapeutic feasibility and potential as clinical targets. The aim is to provide theoretical support for uncovering the novel mechanisms of epigenetic metabolic regulation in CVD and to lay the groundwork for precision intervention strategies.

Background: This study addresses the critical need for timely and accurate diagnosis of early postoperative infection (EPI) following cardiac surgery. EPI significantly impacts patient outcomes and healthcare costs, making its early detection vital. Objectives: To develop, validate, and clinically implement a machine-learning-based model for diagnosing EPI post-cardiac surgery, enhancing postoperative care. Methods: In this multi-center cohort study spanning 2020 to 2022, data from four medical centers involved 2001 participants. Of these, 1400 were used for trainingand 601 for validation. Several machines-learning algorithms, including XGBoost, random forest, support vector machines, least absolute shrinkage and selection operator, and single-layer neural networks, were applied to develop predictive models. These were compared against a traditional logistic regression model. The model with the highest area under the receiver operating characteristic curve (AUROC) was deemed optimal. Implemented across four centers since 1 January 2023, a retrospective real-world study assessed its clinical applicability. Among 400 patients with an estimated EPI risk above 10%, identified by the optimal model, 55 followed its antibiotic upgrade recommendations (DEICS group). The remaining 345 patients upgraded antibiotics empirically, with 55 in the control group, matched 1:1 with the DEICS group. Clinical utility was evaluated through antibiotic use density (AUD), hospital costs, and ICU stay duration. Results: The XGBoost model achieved the highest performance with an AUROC of 0.96 (95% CI: 0.93–0.98). The calibration curve exhibited strong agreement with Brier scores of 0.02. According to the XGBoost model, the DEICS group significantly demonstrated reduced AUD ( P < 0.01) in the matched cohort, along with decreased ICU stay time (median: 5 vs. 6 days, P = 0.01) and hospital costs (median: ¥150 000 vs. median: ¥200 000, P = 0.01) in the EPI cohort. Conclusion: The successful implementation of the XGBoost model facilitates accurate EPI diagnosis, improves postoperative recovery, and lowers hospital costs.

This study aimed to preliminarily investigate the feasibility, safety, and early clinical outcomes of minimally invasive left ventricular assist device (LVAD) implantation with concomitant cardiac procedures. We retrospectively analyzed the clinical data of three consecutive male patients with end-stage heart failure who underwent minimally invasive LVAD implantation at our center between August and November 2024. Two patients received the CorHeart 6 LVAD, while one received the CH-VAD LVAD. Two patients underwent concomitant procedures (patent foramen ovale closure or left atrial appendage occlusion) during the LVAD implantation. All procedures were successfully completed without intraoperative mortality or conversion to sternotomy. Cardiopulmonary bypass time ranged from 121 to 214 min. Postoperative echocardiography demonstrated reduced ventricular dimensions, improved ejection fraction, and resolution of significant valvular regurgitation in all patients. The duration of mechanical ventilation ranged from 1 to 5 days, and the ICU stay ranged from 3 to 7 days. No mortality, pump thrombosis, stroke, or reoperation for bleeding occurred. One patient experienced transient postoperative arrhythmia, which resolved with medical management. This initial experience suggests that minimally invasive LVAD implantation via left thoracotomy, with concomitant cardiac procedures, is technically feasible and safe in selected patients with end-stage heart failure. This strategy was associated with encouraging early outcomes and provides early clinical data on the minimally invasive application of devices such as the CorHeart 6 to the international LVAD community. What is known and what is new? What is the implication, and what should change now?

BACKGROUND:The use of beta-blockers during hospitalization for acute heart failure (AHF) remains controversial. This study aimed to investigate whether beta-blocker use is associated with a reduced risk of mortality in critically ill patients with AHF and to determine the optimal timing for initiating beta-blocker therapy. METHODS:Data from critically ill patients with AHF in the MIMIC-IV version 2.2 database were analyzed. Baseline characteristics, laboratory tests, comorbidities, vital signs, and medication usage at admission and during hospitalization were collected to perform inverse probability of treatment weighting (IPTW). IPTW-weighted logistic regression models were then used to examine the relationship between beta-blocker use and mortality. RESULTS:In the IPTW-weighted regression model, patients who newly started beta-blockers or continued their use had a lower risk of in-hospital mortality compared to those not treated with beta-blockers (odds ratio [OR]: 0.45; 95 % confidence interval [CI]: 0.34 to 0.61, and OR: 0.53; 95 % CI: 0.41 to 0.69, respectively). Conversely, those who had beta-blockers withdrawn showed a higher risk of in-hospital mortality (OR: 2.59; 95 % CI: 1.63 to 4.10). Among beta-blocker users, compared to patients treated before admission and who received their first dose within 48 h of admission, those who were not treated before admission but started after 48 h had a similar mortality risk (OR: 0.82; 95 % CI: 0.60 to 1.11; P = 0.202). However, patients previously treated with beta-blockers who initiated therapy after 48 h and those not treated before admission but started within 48 h had a lower risk of in-hospital mortality (OR: 0.44; 95 % CI: 0.30 to 0.64; P < 0.001, and OR: 0.65; 95 % CI: 0.48 to 0.86; P = 0.003, respectively). CONCLUSION:The use of beta-blockers during hospitalization for AHF is associated with a reduced risk of in-hospital mortality, and withdrawal was associated with an increased risk of mortality. Initiating beta-blockers within 48 h for beta-blocker-naïve patients and after 48 h for those previously treated with beta-blockers before admission may further decrease mortality risk.

BACKGROUND:Donor-derived infections (DDI) represent an inherent risk associated with significant morbidity and mortality in heart transplantation. This study investigated the impact of combined cardiopulmonary donation and the method of dual heart-lung procurement on DDI incidence and short-term outcomes in cardiac transplantation. METHODS:This single-center retrospective study included patients who underwent heart transplantation from January 2021 to February 2025. We excluded multi-organ transplant recipients and recipients receiving donor hearts procured outside Zhongnan Hospital of Wuhan University. Recipients were divided into heart-only procurement group and heart-lung procurement group. The methods of heart-lung procurement were classified as synchronous or sequential procurement. Primary outcomes were the incidence and prognosis of postoperative infection and DDI. Comparisons utilized t-tests, Chi-squared tests, Mann-Whitney U tests, or Fisher's exact tests. p < 0.05 was considered statistically significant. RESULTS:No significant differences were observed in mechanical circulatory support rates, postoperative infection rates, length of hospital stay, or 30-day mortality between the heart-only procurement group (n = 33) and heart-lung procurement group (n = 38). One recipient in the synchronous procurement subgroup developed DDI caused by donor respiratory pathogens; and the overall incidence of DDI at our center was 0.862%. This patient died from septic shock 52 days post-transplantation. CONCLUSIONS:Combined cardiopulmonary donation did not significantly affect the perioperative prognosis of heart transplantation. However, synchronous procurement might increase the risk of DDI derived from respiratory pathogens, which is a rare but fatal complication. Sequential procurement has the potential to avoid this risk and should be the preferred method for dual procurement.

Tissue-engineered cardiac patches (TECPs), which combine cells with biomaterial scaffolds, hold great promise for myocardial repair and regeneration. However, their broader application remains limited by the low survival rate of transplanted cells. To boost the therapeutic efficacy of cardiac patches, genetic engineering and localized delivery of bioactive factors are essential for optimizing cellular function in vivo. In this study, nanofibrous membranes composed of polycaprolactone-co-l-lactide (PLCL) and gelatin at various ratios were fabricated using electrospinning technology. Among these, membranes containing 30% gelatin displayed optimal properties, promoting the adhesion, survival, proliferation, and cardiomyocyte differentiation of induced pluripotent stem cell-derived cardiac progenitor cells (iPSC-CPCs). Following this, TECPs were constructed in vitro and transfected with modified mRNA (modRNA) encoding insulin-like growth factor 1 (IGF1). Further evaluations revealed that IGF1 modified mRNA (modIGF1)-enriched TECPs significantly reduced infarct size, enhanced the survival and proliferation of transplanted cells, promoted vascularization and facilitated cardiac functional recovery. The integration of modRNA technology with myocardial patches facilitates the controlled release of therapeutic proteins, thereby preserving cellular function and offering a promising approach to advancing cardiac tissue engineering.

Supercooling preservation holds great promise for extending the storage limits of organs. However, supercooled systems are susceptible to stochastic ice nucleation, which can cause fatal damage to the organs. In this study, an organogel interface composed of nanoscale polydimethylsiloxane and dimethyl‐silicone oil is proposed, which presents a significant energy barrier for ice nucleation, comparable to that of homogeneous nucleation. The organogel effectively eliminates primary ice nucleation sites, enabling a quasi‐homogeneous supercooling preservation system that does not rely on cryoprotectant agents or machine perfusion. Through a series of statistical experiments, this approach is demonstrated to be able to maintain stable supercooling and preserve mouse hearts at −4 °C for up to 72 h. A comprehensive assessment conducted at multiple scales indicates that the 36‐h supercooling preservation at −4 °C significantly mitigates cardiac injury by regulating mitochondrial structure and reducing metabolic rates. Utilizing a heart transplantation model with prognostic evaluations extending up to 3 months post‐transplantation, supercooling preservation within the quasi‐homogeneous system is confirmed, which can double the storage duration compared to clinically applied hypothermic preservation methods.

The protease method of wool shrink-proofing finishing is challenging to apply industrially due to its low efficiency and prolonged treatment time. In this study, the activator P[(CH2)nOH]3, n is an element of(1, 10) and protease Savinase 16 L were combined and used in the same bath to rapidly degrade wool scales to achieve the target of machine washable for wool. The activator significantly improved the degradation efficiency of 16 L on wool's high-sulfur scale tissue, reducing the wool shrink-proofing treatment time to 100 s. The treated wool samples' area shrinkage, strength, elasticity, length, fineness, and directional friction effect were evaluated. The results showed that the activator combined with Savinase 16 L could rapidly hydrolyze wool fiber scales, and the wool area shrinkage was 1.65 % without excessive damage to the original properties of wool fibers. Furthermore, the reaction mechanism of wool scale degradation by protease and the activator was confirmed by Raman spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results showed that the activator worked by activating the wool high-sulfur scale layer, thereby increasing the efficiency of the protease degradation of wool. It had no activating effect on the protease molecule. The activator opens the disulfide bonds on the wool scales while transforming the beta-thinning and beta-rotation in the scales to alpha-helix or random curling. It could promote protease adsorption and reaction on wool. Under pH 8.0 and 50 degrees C, 2 g/L of activator could increase the adsorption of 16 L on wool by 12.7 times and increase the hydrolysis activity of 16 L on wool by 1575 times. After treatment with this technology, the content of-NH2,-COOH, and-SOx on the surface of wool was increased. Furthermore, a continuous multiple-padding wool shrink-proofing production line was designed, including a treatment liquid circulation and heat preservation systems. Stable industrial production applications were realized.

Objective·To analyze the neurodevelopmental outcomes of children after end-to-side anastomosis for coarctation of the aorta (CoA).Methods·The surgical and neurological follow-up data were collected from children who underwent end-to-side anastomosis for CoA at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 1, 2017 to December 31, 2021. Neurological assessments included magnetic resonance imaging (MRI) and Griffiths Mental Development Scale assessments. Neurodevelopmental outcomes were evaluated using Griffiths Mental Development Scale. Clinical characteristics were compared between patients with normal and abnormal MRI and Griffiths Mental Development Scale results to assess the correlation between the two assessments and their association with cardiopulmonary bypass (CPB) use and CPB modality.Results·Twenty-seven children with isolated CoA or CoA combined with simple intracardiac anomalies were included. MRI results were available for 25 cases, with 5 showing abnormalities (20.0%). Griffiths Mental Development Scale results were available for 26 cases, with 21 (80.77%) showing abnormal scores, including 18 in hearing and language, and 12 in performance. No significant correlation was found between abnormal MRI or Griffiths Mental Development Scale results and the use of CPB (P=0.341, P=1.000). Among patients who underwent CPB, those in the moderate hypothermia group accounted for the majority of cases without neurological abnormalities, with proportions of 80.00% (MRI) and 100.00% (Griffiths Mental Development Scale).Conclusion·Children undergone end-to-side anastomosis for CoA are at relatively high risk for neurodevelopmental abnormalities, particularly in hearing-language and performance domains. CPB may not be a direct risk factor for poor neurodevelopmental outcome, and moderate hypothermia during CPB may be neuroprotective.

Mesenchymal stem cell therapy involves the secretion of various factors to regulate the local microenvironment in various of diseases. This therapy offers hope for treating acute myocardial infarction (MI), which poses a serious threat to human health. However, challenges such as low paracrine efficiency and poor cell survival persist due to the harsh post-infarction conditions, such as hypoxia. Recently, enhanced cell therapy, in which vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor (bFGF) are used as therapeutic agents to limit myocardial injury and simultaneously induce neovascularisation, has been recognised as a promising new strategy to improve the efficacy of cell therapy. Chemically synthetic modified messenger RNA (modRNA), a novel protein expression technology, enables safe, rapid, efficient and pulsatile expression of target proteins in vivo and in vitro settings. It has been widely applied in the fields of vaccine research and tissue regeneration. In this study, human adipose-derived stem cells (hADSCs) were transfected with VEGFA and bFGF modRNA to transiently overexpress these proteins before transplantation. This modification enhanced the paracrine effect of transplanted hADSCs and promoted stability in the vascular network at the transplantation site. Overexpression of VEGFA and bFGF in hADSCs not only inhibited apoptosis but also reduced ventricular remodelling and improved cardiac function and left ventricular conduction. Overall, the additive effects of VEGFA modRNA, bFGF modRNA and hADSCs hold promise for comprehensive cardiac repair post-MI and show substantial potential for treating ischemic heart diseases. KEY POINTS: ModRNAs-transfected hADSCs exhibit pulsed and transient expression, enabling efficient production of functional VEGFA and bFGF proteins. Intracardiac injection of these engineered hADSCs leads to the enhancement of cardiac function and the improvement of electrical conduction. The hADSCsdual mainly exerts its effect on myocardial infarction by promoting stable vascular regeneration and suppressing cell apoptosis.

Abstract Background Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiac defect with high mortality rates, ranging from 9–30%. Surgical repair is the primary treatment, but postoperative complications such as arrhythmias, pulmonary hypertension, and pulmonary vein obstruction persist. Extracorporeal membrane oxygenation (ECMO) has emerged as a critical tool for managing complex cardiac cases, including TAPVC. Methods This retrospective study analyzed patients who received ECMO support postoperatively for TAPVC at Shanghai Children's Medical Center between January 2017 and December 2021. Inclusion criteria were children diagnosed with TAPVC and treated with ECMO. Data on demographics, surgical procedures, ECMO duration, complications, and outcomes were collected. The study followed the Helsinki Declaration. Results A total of 14 TAPVC patients were included, with a median age of 89.5 days and weight of 4.95 kg. The ECMO weaning rate was 85.71%, and the survival rate was 50%. The weaning and survival rates for intracardiac TAPVC were better than other subtypes. Further grouped showed that the high lactate status before ECMO (p = 0.00031) and the fluctuation of APTT value (p = 0.0011) during the ECMO period had predictive significance for the long-term prognosis of these children. Conclusion ECMO support is an effective therapy for TAPVC patients facing postoperative complications. Higher pre-ECMO lactate levels and fluctuations in APTT values during ECMO were predictive of long-term prognosis.

OBJECTIVES:To analyze the clinical outcomes of extracorporeal membrane oxygenation (ECMO) support in children with congenital heart disease (CHD) after surgery and explore the risk factors associated with mortality during long-term follow-up for 3-5 years. METHODS:We conducted a retrospective observational study at Shanghai Children Medical Center (SCMC) from 2017 to 2021 and reviewed the clinical results and laboratory findings of 188 CHD patients who received ECMO support during this period. RESULTS:The 5-year overall survival rate was 56.38% (106/188) among CHD patients who received ECMO support. Kaplan-Meier curve showed residual anatomical malformation (RAM) (p < 0.0001), gastrointestinal bleeding (p = 0.019), single ventricular (SV) (p = 0.028), and pre-ECMO lactate level >10 mmol/L (p < 0.0001) were significantly associated with higher mortality in follow-up. Cox analysis identified RAM (p = 0.039) and pre-ECMO lactate level >10 mmol/L (p < 0.001) as independent risk factors for overall survival. Conversely, a minimum platelet count ≥50 × 109/L (p < 0.001) was found to be a protective factor. Moreover, a competing risk model showed that a CPR time ≥60 min (p < 0.001) was identified as a risk factor for death in patients who failed to be discharged from the hospital. CONCLUSIONS:Our study showed characteristics of long-term follow-up patients and revealed several risk factors associated with mortality in children with CHD who received ECMO support. These findings can provide valuable insights for clinical decision-making and contribute to improving patient outcomes.

Background With the decline of birth population and the development of medical technology in China, studies assessing how these changes have affected the adoption of congenital heart disease surgery at the national or regional scale are lacking. Methods We investigated the status of congenital heart surgery in China in the period from 2017–2022, through investigation of the total rates of cardiac surgeries, cardiopulmonary bypass (CPB), adult congenital heart surgeries (CHS), and pediatric CHS (<18 years old), as recorded by the Extracorporeal Circulation Branch of the Chinese Society of Biomedical Engineering. Subsequently, we evaluated correlations between these factors with economic, demographic, and other factors. Results From 2017 to 2022, the total number of cardiac operations increased from 230,772 to 263,292, representing an increase of 14.09% over 6 years; the CHS dropped from 76,365 to 68,940 (10.19% decrease), and the proportion of CHS in the total cardiac surgeries dropped from 33.26% to 26.18% (7.08% decrease). Finally, cases of pediatric CHS decreased from 61,825 to 38,174 (38.25% decrease). The annual percentage change (APC) of the total amount of pediatric CHS cases was –10.03 (–15.95 to –3.69, p = 0.013). Adult CHS increased from 14,940 to 30,766 (105.93% increase). The proportion of adult CHS cases of the total number of cardiac surgeries increased from 6.47% to 11.68% (5.21% increase). From a regional perspective, the APC for the proportion of pediatric CHS in the local population was generally lower in western China. The proportion of CHS in the local population generally decreases from the north to the south, although the lowest incidence is found in the northeast region. Conclusions Due to demographic changes, medical technology and economic factors, the number of surgical operations for congenital heart disease (CHD) in children decreased significantly from 2017 to 2022, and may decline further in the future. Nevertheless, in the same period, a significant increase in the number of operations for CHD in adults was observed, which brings new opportunities and challenges to the development of congenital cardiac surgery and cardiac critical care.

Three-dimensional (3D) printing of "bioinks"containing living cells has broad prospects in the fields of in vitro modeling and regenera-tive medicine. However, existing bioinks lack a number of required properties, including antibacterial characteristics, long-term shape maintenance, and cytoprotection ability during fabrication, cryo-preservation, and transportation of 3D bioprinted tissues. In this study, we created a multifunctional glycerohydrogel bioink to address these challenges. The key is using glycerol to regulate the state of water in the bioink. Glycerohydrogels with limited "free wa-ter"exhibited significant inhibition of Escherichia coli and mold, outstanding shape maintenance, excellent compatibility with 3T3 mouse fibroblasts and rat adipose-derived stem cells, and an intrinsic ability of cryopreservation at -80 degrees C, which is superior to ex-isting hydrogel-based bioinks. This work provides a design principle for bioinks by regulating molecular interactions and will have broad prospects for practical biomedical applications.

Artificial skin substitutes are one of the most promising areas of wound healing research; however, graft survival largely depends on how the treatment is performed. Early angiogenesis is essential for wound healing and graft survival and vascular endothelial growth factor A (VEGFA) is an important cytokine that stimulates angiogenesis. Here, we first investigated the effects of different ratios of collagen (BC) and gelatin blended with poly (L-lactideco-caprolactone) (PLCL) on nanofibrous membranes. The Young's modulus and cell proliferation were significantly higher in the 50% BC group than that in all other groups. Then, cellular electrospun membrane complexes (CEMC) were successfully constructed from nanoscaffolds and fibroblasts extracted from human foreskin and engineered with controlled autocrine VEGFA by transfecting VEGFA modified mRNA (modRNA). Engineered CEMC significantly promoted wound healing in vivo and contributed to stable vascular network formation in the grafted area, thereby increasing the survival rate of the engineered skin. This study provides a potential solution for wound healing while establishing the value of different RNA modification methods for various engineered skins in the future, thereby advancing engineered skin development.

Engineering a conduction-consistent cardiac patch has direct implications to biomedical research. However, there is difficulty in obtaining and maintaining a system that allows researchers to study physiologically relevant cardiac development, maturation, and drug screening due to the issues around inconsistent contractions of cardiomyocytes. Butterfly wings have special nanostructures arranged in parallel, which could help generate the alignment of cardiomyocytes to better mimic the natural heart tissue structure. Here, we construct a conduction-consistent human cardiac muscle patch by assembling human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on graphene oxide (GO) modified butterfly wings. We also show this system functions as a versatile model to study human cardiomyogenesis by assembling human induced pluripotent stem cell-derived cardiac progenitor cells (hiPSC-CPCs) on the GO modified butterfly wings. The GO modified butterfly wing platform facilitated the parallel orientation of hiPSC-CMs, enhanced relative maturation as well as improved conduction consistency of the cardiomyocytes. In addition, GO modified butterfly wings enhanced the proliferation and maturation characteristics of the hiPSC-CPCs. In accordance with data obtained from RNA-sequencing and gene signatures, assembling hiPSC-CPCs on GO modified butterfly wings stimulated the differentiation of the progenitors into relatively mature hiPSC-CMs. These characteristics and capabilities of GO modified butterfly wings make them an ideal platform for heart research and drug screening.