The treatment of difficult-to-heal wounds remains a substantial clinical challenge due to deteriorative tissue microenvironment including the loss of extracellular matrix (ECM), excessive inflammation, impaired angiogenesis, and bacterial infection. Inspired by the chemical components, fibrous structure, and biological function of natural ECM, antibacterial and tissue environment–responsive glycopeptide hybrid hydrogel was developed for chronic wound healing. The hydrogel can facilitate the cell proliferation and macrophage polarization to M2 phenotype, and show potent antibacterial efficacy against both Gram-negative and Gram-positive bacteria. Significantly, the glycopeptide hydrogel accelerated the reconstruction of methicillin-resistant Staphylococcus aureus (MRSA)–infected full-thickness diabetic and scalding skin by orchestrating a pro-regenerative response indicated by abundant M2-type macrophages, attenuated inflammation, and promoted angiogenesis. Collectively, ECM-mimetic and immunomodulatory glycopeptide hydrogel is a promising multifunctional dressing to reshape the damaged tissue environment without additional drugs, exogenous cytokines, or cells, providing an effective strategy for the repair and regeneration of chronic cutaneous wounds.

Stem cell-derived exosomes have been recognized as a potential therapy for cardiovascular disease. However, the low retention rate of exosomes after transplantation in vivo remains a major challenge in clinical applications. The aim of this study is to investigate whether human umbilical cord mesenchymal stem cell derived exosomes (UMSC-Exo) encapsulated in functional peptide hydrogels could increase the retention and stability of exosomes and improve heart function in a rat myocardial infarction model. Our results demonstrated that the PA-GHRPS peptide protected H9C2 cells from H₂O₂-induced oxidative stress. The gelatinization ability of PA-GHRPS can be enhanced by peptide NapFF. Therefore, these two peptides were mixed to form the PGN hydrogel, which was used to encapsulate exosomes. Our data showed that the PGN hydrogel was able to encapsulate exosomes effectively and ensured a stable and sustained release of exosomes. The exosome/PGN hydrogel mixture was injected into the infarcted border zone of rat hearts. Compared to the exosome treatment alone, the mixture improved the myocardial function by reducing inflammation, fibrosis and apoptosis, and by promoting angiogenesis. The strategy used in this study provided a practical and effective method to harness exosomes for myocardial regeneration.

China is in the midst of an epidemiological transition in which cardiovascular diseases (CVDs) have replaced infectious diseases as the leading cause of death.¹ Currently, CVD in China accounts for more than 40% of the causes of death.² There are concerns that dyslipidemia, the prevalence of which historically was low in China, is emerging as the second leading yet often unaddressed factor associated with the risk of CVD.³

Ischaemic heart disease (IHD) and ischaemic stroke are leading causes of death worldwide. Although extensively studied, previous research has predominantly addressed these two diseases in isolation. Comorbidity research faces challenges both at the patient level and in terms of study methods. We aimed to characterise the global co-occurrence pattern of IHD and ischaemic stroke from a spatial perspective and to identify the corresponding risk factors of the comorbidity. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 database, we extracted incidence rates of IHD and ischaemic stroke and exposure rates of the 68 most detailed risk factors among individuals aged 25 years or older from 203 countries and territories. Based on the four quartiles of global incidence rates for both diseases, we proposed the comorbidity's co-occurrence patterns and classified the 203 countries or territories into three distinct regions (consistent, IHD-dominant, and ischaemic stroke-dominant areas). We used machine learning and negative binomial regression to screen and quantify the effects of corresponding risk factors and computed the population-attributable fraction and composite risk index to evaluate the global disease burden of IHD and ischaemic stroke. 89 countries were classified as consistent, 59 as IHD-dominant, and 55 as ischaemic stroke-dominant. The spatial distribution of the three co-occurrence patterns overlapped with exposure to environmental, dietary, and behavioural risk factors. Nine risk factors were identified and functionally classified into common and specific features. Most countries are simultaneously exposed to the combined effects of multiple risk factors. Overall, 45·43% of IHD incidence and 38·53% of ischaemic stroke incidence is attributable to cumulative exposure to the respective risk factors, with specific combinations and variations of these factors greatly influencing the global disparities and patterns of incidence. The comorbidity of IHD and ischaemic stroke is a pervasive global health issue. Intervening corresponding modifiable risk factors can fundamentally reduce the global burden of these diseases. National High Level Hospital Clinical Research Funding.

The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage‐endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.