Progress of organoid platform in cardiovascular research.

Cardiovascular disease is a significant cause of death in humans. Various models are necessary for the study of cardiovascular diseases, but once cellular and animal models have some defects, such as insufficient fidelity. As a new technology, organoid has certain advantages and has been used in many applications in the study of cardiovascular diseases. This article aims to summarize the application of organoid platforms in cardiovascular diseases, including organoid construction schemes, modeling, and application of cardiovascular organoids. Advances in cardiovascular organoid research have provided many models for different cardiovascular diseases in a variety of areas, including myocardium, blood vessels, and valves. Physiological and pathological models of different diseases, drug research models, and methods for evaluating and promoting the maturation of different kinds of organ tissues are provided for various cardiovascular diseases, including cardiomyopathy, myocardial infarction, and atherosclerosis. This article provides a comprehensive overview of the latest research progress in cardiovascular organ tissues, including construction protocols for cardiovascular organoid tissues and their evaluation system, different types of disease models, and applications of cardiovascular organoid models in various studies. The problems and possible solutions in organoid development are summarized.

Evolution of the network structure and voltage loss of anode electrode with the polymeric dispersion in PEM water electrolyzer.

Exploring the intrinsic relationship between the network structure and the performance of catalyst layer (CL) by rational design its structure is of paramount importance for proton exchange membrane (PEM) electrolyzers. This study reveals the relative effect of polymeric dispersion evolution on oxygen evolution reaction (OER) performance and cell voltage loss and linked to CL network structure. The results show that although the dispersed particle size of the ionomer and ink increases with increasing the solubility parameter (δ) difference between the mixed solvent and the ionomer, MeOH-cat (ink from MeOH aqueous solution) has the largest ionomer and ink particle size resulting in the poorest stability, but has comparable OER overpotential to that of IPA-cat (249 mV@10 mA cm-2), which has the smallest dispersed size. While at 100 mA cm-2, the overpotential of the ink rises as the particle size increases, suggesting that the electrode structure becomes more influential as the current density increases. Quantitatively analyzed the electrolyzers' voltage losses and determined that the CL from MeOH-cat has the lowest kinetic overpotential. However, its performance is the worst because of the insufficient network structure of CL, resulting in an output of 1.96 V at 1.5 A cm-2. Comparatively, the CL from IPA-cat has the highest kinetic overpotential yet can achieve the greatest performance of 1.76 V at 2 A cm-2 due to its homogeneous network structure and optimal mass transport. Furthermore, the performance variation becomes more pronounced as current density rises. Hence, this study highlights the significant impact of CL structure on electrolyzer's performance. To improve performance in PEM water electrolysis technology, especially for large work current density, it is crucial to enhance the CL's network structure.

Genetic variations in PTPN11 lead to a recurrent Left Ventricular Outflow Tract Obstruction phenotype in childhood hypertrophic cardiomyopathy.

OBJECTIVE: Left ventricular septal myotomy provides a favorable prognosis for children with hypertrophic obstructive cardiomyopathy (HOCM). However, some children still suffer from recurrent left ventricular outflow tract obstruction (LVOTO) after surgery. Poor prognosis exists for HOCM caused by PTPN11 mutation. Therefore, the aim of this study was to determine the clinical features of recurrent obstruction in children with HOCM caused by pathogenic mutations in the PTPN11 gene. METHODS: A total of 56 children were diagnosed with HOCM underwent septal myectomies. Whole exome sequencing of 49 pediatric cardiomyopathies associated genes (including PTPN11) were performed. We performed hematoxylin-eosin(H&E), Masson, and wheat germ agglutinin (WGA)staining of tissues positive for PTPN11 and those negative for PTPN11 were conducted. RESULTS: Whole exome sequencing results showed 11 PTPN11 mutation (19.6%) children. In long-term follow-up (median 37 months, maximum 9 years), children with PTPN11 mutation had 6(54.5%) recurrent LVOTO compared with other groups (P=.015), but similar survival rates(P=.514). The mean postoperative time to recurrent obstruction was 22±27 months. Children with PTPN11 mutation were 9-fold more likely to experience the risk associated with recurrent obstruction (95% CI = 1.77-45.81, P<.001). H&E, Masson and WGA staining also revealed more cardiomyocyte hypertrophy in PTPN11 mutation tissues. See Figure 4 for a graphical abstract of the study. CONCLUSION: Children with PTPN11 mutation-associated hypertrophic cardiomyopathy have a higher risk of recurrent LVOTO.

Overexpression of ATP5F1A in Cardiomyocytes Promotes Cardiac Reverse Remodeling.

BACKGROUND: The mechanism of cardiac reverse remodeling (CRR) mediated by the left ventricular assist device remains unclear. This study aims to identify the specific cell type responsible for CRR and develop the therapeutic target that promotes CRR. METHODS: The nuclei were extracted from the left ventricular tissue of 4 normal controls, 4 CRR patients, and 4 no cardiac reverse remodeling patients and then subjected to single-nucleus RNA sequencing for identifying key cell types responsible for CRR. Gene overexpression in transverse aortic constriction and dilated cardiomyopathy heart failure mouse model (C57BL/6J background) and pathological staining were performed to validate the results of single-nucleus RNA sequencing. RESULTS: Ten cell types were identified among 126 156 nuclei. Cardiomyocytes in CRR patients expressed higher levels of ATP5F1A than the other 2 groups. The macrophages in CRR patients expressed more anti-inflammatory genes and functioned in angiogenesis. Endothelial cells that elevated in no cardiac reverse remodeling patients were involved in the inflammatory response. Echocardiography showed that overexpressing ATP5F1A through cardiomyocyte-specific adeno-associated virus 9 demonstrated an ability to improve heart function and morphology. Pathological staining showed that overexpressing ATP5F1A could reduce fibrosis and cardiomyocyte size in the heart failure mouse model. CONCLUSIONS: The present results of single-nucleus RNA sequencing and heart failure mouse model indicated that ATP5F1A could mediate CRR and supported the development of therapeutics for overexpressing ATP5F1A in promoting CRR.

On-surface conversion reaction realizes advanced red phosphorus/carbon anode for high-performance lithium-ion batteries.

Red phosphorus (RP), the one of the most prospective anodes in lithium-ion batteries (LIBs), has been severely limited due to the intrinsic defects of massive volume expansion and low electronic conductivity. The vaporization-condensation-conversion (VCC), which confines RP nanoparticles into carbon host, is the most widely used method to address the above drawbacks and prepare RP/C nanostructured composites. However, the volume effect-dominated RP caused by the inevitably deposition of RP vapor on the surface of carbon material suffers from the massive volume change and unstable solid electrolyte interface (SEI) film. Herein, we propose a simple interfacial modification method to eliminate the superficial RP and yield stable surface composed of ion-conducting Li3PS4 solid electrolyte, endowing RP/AC composites excellent cycling performance and ultrafast reaction kinetics. Therefore, the RP/AC@S composites exhibit 926 mAh/g after 320 cycles at 0.2 A/g (running over 181 days), with 81.6 % capacity retention and a corresponding capacity decay rate of as low as 0.059 %. When coupled with LiFePO4 cathode, the full cells present superior cycling performance (62.1 mAh/g after 500 cycles at 1 A/g) and excellent rate capability (81.1 mAh/g at 1.0 A/g).

Left ventricular posterior wall hypertrophy leads to poor prognosis of hypertrophic obstructive cardiomyopathy in children - a cohort study.

OBJECTIVE: The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis. METHODS: We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors. RESULTS: 17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation (HR:5.634, 95%CI:1.663-19.086, P=0.005), Noonan syndrome (HR:3.770, 95%CI:1.245-11.419, P=0.019), preoperational systolic anterior motion (SAM)(HR:4.596, 95%CI:1.532-13.792, P=0.007)and mid-ventricular obstruction (HR:4.763, 95%CI:1.538-14.754, P=0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior (P=0.014), mid-inferoseptal(P=0.044), mid-inferior(P=0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis. CONCLUSION: Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.

New insights gained from cellular landscape changes in myocarditis and inflammatory cardiomyopathy.

Advances in the etiological classification of myocarditis and inflammatory cardiomyopathy (ICM) have reached a consensus. However, the mechanism of myocarditis/ICM remains unclear, which affects the development of treatment and the improvement of outcome. Cellular transcription and metabolic reprogramming, and the interactions between cardiomyocytes and non-cardiomyocytes, such as the immune cells, contribute to the process of myocarditis/ICM. Recent efforts have been made by multi-omics techniques, particularly in single-cell RNA sequencing, to gain a better understanding of the cellular landscape alteration occurring in disease during the progression. This article aims to provide a comprehensive overview of the latest studies in myocarditis/ICM, particularly as revealed by single-cell sequencing.

PICALM Regulating the Generation of Amyloid ß-Peptide to Promote Anthracycline-Induced Cardiotoxicity.

Anthracyclines are chemotherapeutic drugs used to treat solid and hematologic malignancies. However, life-threatening cardiotoxicity, with cardiac dilation and heart failure, is a drawback. A combination of in vivo for single cell/nucleus RNA sequencing and in vitro approaches is used to elucidate the underlying mechanism. Genetic depletion and pharmacological blocking peptides on phosphatidylinositol binding clathrin assembly (PICALM) are used to evaluate the role of PICALM in doxorubicin-induced cardiotoxicity in vivo. Human heart tissue samples are used for verification. Patients with end-stage heart failure and chemotherapy-induced cardiotoxicity have thinner cell membranes compared to healthy controls do. Using the doxorubicin-induced cardiotoxicity mice model, it is possible to replicate the corresponding phenotype in patients. Cellular changes in doxorubicin-induced cardiotoxicity in mice, especially in cardiomyocytes, are identified using single cell/nucleus RNA sequencing. Picalm expression is upregulated only in cardiomyocytes with doxorubicin-induced cardiotoxicity. Amyloid ß-peptide production is also increased after doxorubicin treatment, which leads to a greater increase in the membrane permeability of cardiomyocytes. Genetic depletion and pharmacological blocking peptides on Picalm reduce the generation of amyloid ß-peptide. This alleviates the doxorubicin-induced cardiotoxicity in vitro and in vivo. In human heart tissue samples of patients with chemotherapy-induced cardiotoxicity, PICALM, and amyloid ß-peptide are elevated as well.

Advances in preclinical surgical therapy of cardiovascular diseases.

Cardiovascular disease is the most common cause of death worldwide, resulting in millions of deaths annually. Currently, there are still some deficiencies in the treatment of cardiovascular diseases. Innovative surgical treatments are currently being developed and tested in response to this situation. Large animal models, which are similar to humans in terms of anatomy, physiology, and genetics, play a crucial role in connecting basic research and clinical applications. This article reviews recent preclinical studies and the latest clinical advancements in cardiovascular disease based on large animal models, with a focus on targeted delivery, neural regulation, cardiac remodeling, and hemodynamic regulation. It provides new perspectives and ideas for clinical translation and offers new methods for clinical treatment.

Isolated Perfused Hearts for Cardiovascular Research: An Old Dog with New Tricks.

In modern cardiovascular research, isolated perfused hearts have become cost-effective and highly reproducible tools to investigate the mechanisms of cardiovascular diseases (CVDs). Since they were first introduced in the nineteenth century, isolated perfused hearts have been extensively used for testing novel therapies, elucidating cardiac metabolic and electrophysiological activities, and modeling CVDs, including ischemic heart disease, arrhythmias, and hyperacute rejection. In recent years, ex vivo heart perfusion (EVHP) has shown potential in cardiac transplantation by allowing prolonged preservation and reconditioning of donor hearts. In this review, we summarize the evolution of the isolated perfused heart technique and its applications in cardiovascular research to help researchers comprehensively understand the capabilities of isolated heart models and provide guidance to use them to investigate various CVDs.

Inhibition of fatty acid uptake by TGR5 prevents diabetic cardiomyopathy.

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.

Single-Cell Transcriptomic Analysis Reveals Myocardial Fibrosis Mechanism of Doxorubicin-Induced Cardiotoxicity.

Myocardial fibrosis is a pathological feature of doxorubicin-induced chronic cardiotoxicity that severely affects the prognosis of oncology patients. However, the specific cellular and molecular mediators driving doxorubicin-induced cardiac fibrosis, and the relative impact of different cell populations on cardiac fibrosis, remain unclear.This study aimed to explore the mechanism of doxorubicin-induced cardiotoxicity and myocardial fibrosis and to find potential therapeutic targets. Single-cell RNA sequencing was used to analyze the transcriptome of non-cardiomyocytes from normal and doxorubicin-induced chronic cardiotoxicity in mouse model heart tissue.We established a mouse model of doxorubicin-induced cardiotoxicity with a well-defined fibrotic phenotype. Analysis of single-cell sequencing results showed that fibroblasts were the major origin of extracellular matrix in doxorubicin-induced myocardial fibrosis. Further resolution of fibroblast subclusters showed that resting fibroblasts were converted to matrifibrocytes and then to myofibroblasts to participate in the myocardial remodeling process in response to doxorubicin treatment. Ctsb expression was significantly upregulated in fibroblasts after doxorubicin-induced.This study provides a comprehensive map of the non-cardiomyocyte landscape at high resolution, reveals multiple cell populations contributing to pathological remodeling of the cardiac extracellular matrix, and identifies major cellular sources of myofibroblasts and dynamic gene-expression changes in fibroblast activation. Finally, we used this strategy to detect potential therapeutic targets and identified Ctsb as a specific target for fibroblasts in doxorubicin-induced myocardial fibrosis.

The pig as an optimal animal model for cardiovascular research.

Cardiovascular disease is a worldwide health problem and a leading cause of morbidity and mortality. Preclinical cardiovascular research using animals is needed to explore potential targets and therapeutic options. Compared with rodents, pigs have many advantages, with their anatomy, physiology, metabolism and immune system being more similar to humans. Here we present an overview of the available pig models for cardiovascular diseases, discuss their advantages over other models and propose the concept of standardized models to improve translation to the clinical setting and control research costs.

Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy.

To solve the clinical transformation dilemma of lamin A/C (LMNA)-mutated dilated cardiomyopathy (LMD), we developed an LMNA-mutated primate model based on the similarity between the phenotype of primates and humans. We screened out patients with LMD and compared the clinical data of LMD with TTN-mutated and mutation-free dilated cardiomyopathy to obtain the unique phenotype. After establishment of the LMNA c.357-2A>G primate model, primates were continuously observed for 48 months, and echocardiographic, electrophysiological, histologic, and transcriptional data were recorded. The LMD primate model was found to highly simulate the phenotype of clinical LMD. In addition, the LMD primate model shared a similar natural history with humans.

A Heterozygous Phospholamban Variant (p.R14del) Leads to Left Ventricular Involvement and Heart Failure Phenotypes in Arrhythmogenic Right Ventricular Cardiomyopathy.

This study aimed to determine the prevalence and clinical features of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) caused by pathogenic mutations in the Phospholamban (PLN) gene. The study included 170 patients who had a confirmed diagnosis of ARVC and underwent PLN genetic screening using next-generation sequencing. The findings of this study provide valuable insights into the association between PLN mutations and ARVC, which can aid in the development of more effective diagnostic and treatment strategies for ARVC patients. Out of the patients evaluated, six had a rare pathogenic mutation in PLN with the same p.R14del variant. Family screening revealed that heterozygous carriers of p.R14del exhibited a definite ARVC phenotype. In clinical studies, individuals with the p.R14del mutation experienced a similar rate of malignant arrhythmia events as those with classic desmosome mutations. After adjusting for covariates, individuals with PLN mutations had a two point one seven times greater likelihood of experiencing transplant-related risks compared to those who did not possess PLN mutations (95% CI 1.08-6.82, p = 0.035). The accumulation of left ventricular fat and fibers is a pathological marker for ARVC patients with p.R14del mutations. In a cohort of 170 Chinese ARVC patients, three point five percent of probands had the PLN pathogenic variant (p.R14del) and all were female. Our data shows that PLN-related ARVC patients are at high risk for ventricular arrhythmias and heart failure, which requires clinical differentiation from classic ARVC. Furthermore, carrying the p.R14del mutation can be an independent prognostic risk factor in ARVC patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00126-w.

PBX/Knotted 1 homeobox-2 (PKNOX2) is a novel regulator of myocardial fibrosis.

Much effort has been made to uncover the cellular heterogeneities of human hearts by single-nucleus RNA sequencing. However, the cardiac transcriptional regulation networks have not been systematically described because of the limitations in detecting transcription factors. In this study, we optimized a pipeline for isolating nuclei and conducting single-nucleus RNA sequencing targeted to detect a higher number of cell signal genes and an optimal number of transcription factors. With this unbiased protocol, we characterized the cellular composition of healthy human hearts and investigated the transcriptional regulation networks involved in determining the cellular identities and functions of the main cardiac cell subtypes. Particularly in fibroblasts, a novel regulator, PKNOX2, was identified as being associated with physiological fibroblast activation in healthy hearts. To validate the roles of these transcription factors in maintaining homeostasis, we used single-nucleus RNA-sequencing analysis of transplanted failing hearts focusing on fibroblast remodelling. The trajectory analysis suggested that PKNOX2 was abnormally decreased from fibroblast activation to pathological myofibroblast formation. Both gain- and loss-of-function in vitro experiments demonstrated the inhibitory role of PKNOX2 in pathological fibrosis remodelling. Moreover, fibroblast-specific overexpression and knockout of PKNOX2 in a heart failure mouse model induced by transverse aortic constriction surgery significantly improved and aggravated myocardial fibrosis, respectively. In summary, this study established a high-quality pipeline for single-nucleus RNA-sequencing analysis of heart muscle. With this optimized protocol, we described the transcriptional regulation networks of the main cardiac cell subtypes and identified PKNOX2 as a novel regulator in suppressing fibrosis and a potential therapeutic target for future translational studies.

A single-cell atlas of lung homeostasis reveals dynamic changes during development and aging.

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung's development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.

[Genetic background of lily germplasm resources based on SSR markers].

To study the genetic background of lily (Lilium spp.) germplasm resources, and accurately evaluate and select excellent germplasm for genetic improvement of lily, we analyzed the genetic background of 62 lily germplasm accessions from 11 provinces of China by using simple sequence repeat (SSR) molecular markers. The results showed that 15 out of 83 pairs of lily SSR primers were polymorphic. A total of 157 allelic loci were amplified, with the number of alleles per locus ranging from 5 to 19 and the average number of effective alleles per locus being 4.162 8. The average observed heterozygosity and expected heterozygosity were 0.228 2 and 0.694 1, respectively. The average polymorphic information content was 0.678 8. The average Nei's diversity index and Shannon's information index were 0.694 1 and 1.594 9, respectively, indicating that the tested lily germplasm had high genetic diversity. The 62 germplasm accessions were classified into 5 groups by the unweighted pair group method with arithmetic mean (UPGMA) and into 3 groups by the principal component analysis. The two analyses revealed a geographic correlation among different groups. The majority of lily germplasm accessions from the same source tended to cluster together. The population structure analysis classified the lily accessions into 4 populations and 1 mixed population. The above results provide a theoretical basis and genetic resources for the precise identification and breeding of lily germplasm resources.

Injuries of Different Surgical Instruments on the Vocal Folds of Dogs.

OBJECTIVE: This study aimed to compare the damage of vocal folds caused by four different surgical instruments: CO2 laser, electrosurgical knife, plasma radiofrequency ablation, and steel knife. STUDY DESIGN: Randomized controlled study. METHODS: The CO2 laser, electrosurgical knife, plasma radiofrequency ablation, steel knife, and other instruments were used to simulate the laryngeal microsurgery on experimental dogs. Both total vocal fold resection and punctate ablation were performed. On the day of surgery and 6 days later, the vocal fold tissue from the surgical site was removed for histological evaluation. The extent of vocal fold damage was assessed using the automatic digital pathological scanning system. RESULTS: We detected varying degrees of damage to the laryngeal tissues. Only the steel knife caused epidermal defects on the vocal fold tissue, while other instruments produced thermal damage of different degrees. Furthermore, the steel knife also showed better and faster healing. The plasma radiofrequency ablation was found to cause more severe thermal burns to vocal folds than other surgical instruments (P < 0.05). Six days postsurgery the inflammatory reaction from the steel knife had basically subsided, with only hyperplasia and tissue repair visible microscopically, showing the best healing degree. On the other hand, the radiofrequency ablation group showed the heaviest inflammatory reaction, indicating relatively poor prognosis (P < 0.05). CONCLUSION: Compared with the CO2 laser, the electrotome and steel knife showed less damage and better healing, while the plasma radiofrequency ablation showed the most obvious thermal burns to laryngeal and vocal tissues during surgery, with relatively poor healing.

Highly active probiotic hydrogels matrixed on bacterial EPS accelerate wound healing via maintaining stable skin microbiota and reducing inflammation.

Skin microbiota plays an important role in wound healing, but skin injuries are highly susceptible to wound infections, leading to disruption of the skin microbiota. However, conventional antibacterial hydrogels eliminate both probiotics and pathogenic bacteria, disrupting the balance of the skin microbiota. Therefore, it is important to develop a wound dressing that can fend off foreign pathogenic bacteria while preserving skin microbiota stability. Inspired by live bacteria therapy, we designed a probiotic hydrogel (HAEPS@L.sei gel) with high viability for promoting wound healing. Lactobacillus paracasei TYM202 encapsulated in the hydrogel has the activity of promoting wound healing, and the hydrogel matrix EPS-M76 has the prebiotic activity that promotes the proliferation and metabolism of Lactobacillus paracasei TYM202. During the wound healing process, HAEPS@L.sei gel releases lactic acid and acetic acid to resist the growth of pathogenic bacteria while maintaining Firmicutes and Proteobacteria balance at the phylum level, thus preserving skin microbiota stability. Our results showed that live probiotic hydrogels reduce the incidence of inflammation during wound healing while promoting angiogenesis and increasing collagen deposition. This study provides new ideas for developing wound dressings predicated on live bacterial hydrogels.