Immunomodulatory microneedles restore mitochondrial homeostasis and balance TGF-β/TNF-α signaling to accelerate diabetic wound repair

Sep 30, 2026

Uploaded by Eliana

Diabetic infected wounds impose major physical and psychological burdens because high-glucose conditions favor pathogens, weaken host defenses, and promote biofilms that traditional repair materials cannot penetrate or reprogram. A bilayer sulfonated chitosan/methacrylated hyaluronic acid/methacrylated collagen III microneedle system loaded with MXene@Zn-MOF was designed for antibacterial action and immune microenvironment regulation. The system inhibited E. coli and S. aureus, removed biofilms, promoted angiogenesis via TGF-β signaling, shifted macrophages toward M2 while suppressing TNF-α–mediated inflammation, and restored ROS-reduced mitochondrial function, with transcriptome evidence supporting mechanism-driven wound repair.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Article overview

Design of bilayer microneedle system

Antibacterial and anti-biofilm performance

Immune regulation via TGF-β and TNF-α pathways

Macrophage polarization and inflammation control

Mitochondrial function and ROS-related effects

Transcriptome analysis and mechanism elucidation

Introduction

Diabetes-related immune and vascular dysfunction

Challenges of infected, biofilm-associated wounds

Limitations of current clinical treatments

Materials Today Bio 36 (2026) 102687 Contents lists available at ScienceDirect Materials Today Bio journal [homepage:](homepage: www.journals.elsevier.com/materials-today-bio)[ www.journals.elsevier.com/materials-today-bio](homepage: www.journals.elsevier.com/materials-today-bio) | Immunomodulatory microneedles restore mitochondrial homeostasis and balance TGF-β/TNF-α signaling to accelerate diabetic wound repair
Minjian Liao a,1, Xinmin Guob,1, Longbao Feng a, Qing Pengc, Jianhao Lianga, Aleh Kuzniatsoud, Rui Guo a,* , Pan Yue,** , Shuqin Zhou f,g,***
a Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Key Laboratory of Regenerative Medicine of Ministry of Education, Guangdong Provincial Engineering and Technological Research Centre for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China b Department of Ultrasound, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, 510220, China
c Central Laboratory of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, 518172, China
d Institute of Biochemistry of Biologically Active Compounds of the National Academy of Sciences of Belarus, Grodno, Belarus
e Department of Burn and Plastic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
f Department of Anesthesiology of The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen & Longgang District People’s Hospital of Shenzhen, Shenzhen, 518172, China
g Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510000, China | | | | --- | --- | --- | | A R T I C L E I N F O | | A B S T R A C T | | Keywords:
MXene@Zn-MOF
Dual-layer microneedles TGF-β signaling pathways Diabetic wound | | Diabetic infected wounds bring great physical and psychological burden to patients. To solve this problem, removing bacteria and regulating the local immune microenvironment have become effective measures. However, traditional wound repair materials are difficult to break through the bacterial biofilm covering the wound site and thus cannot effectively regulate the internal immune environment of the wound. A bilayer multifunctional sulfonated chitosan (SCS)/methacrylated hyaluronic acid (HAMA)/methacrylated collagen III (Col IIIMA)(SCS/HAMA/Col IIIMA, SHC) microneedle loaded with MXene@Zn-MOF (MXZ) composite was designed for diabetic infected wound repair. The MXZ composite achieved more than 99 % bacterial inhibition against both E. coli and S. aureus, and was able to effectively remove the bacterial biofilm. In addition, SHC + MXZ microneedles were able to promote angiogenesis by activating the Transforming Growth Factor-β (TGF-β) signaling pathway. It also regulated macrophage polarization towards the M2 phenotype and inhibited the Tumor Necrosis Factor-α (TNF-α) signaling pathway to reduce the level of inflammation. Further studies on mitochondrial membrane potential showed that SHC + MXZ microneedles were able to restore the decrease in mitochondrial membrane potential caused by ROS and then restore mitochondrial function. In diabetic infected wound repair results showed that SHC + MXZ microneedles effectively promoted diabetic infected wound repair by promoting angiogenesis and reducing the inflammation level of the wound tissue. Finally, the regulation of related gene expression was explored by transcriptome sequencing, and the intrinsic mechanism of SHC MXZ microneedles in promoting the repair of diabetic infected wounds by regulating the TGF-β and TNF-α signaling pathways was elucidated. | 1. Introduction Diabetes has become a global metabolic disease, and according to the International Diabetes Federation’s 2021 statistics, the cumulative number of patients worldwide has reached 537 million, resul

FAQs

What problem do the microneedles aim to solve in diabetic infected wounds?

They target the difficulty of removing bacterial biofilms and the failure of conventional materials to effectively regulate the local immune microenvironment under high-glucose conditions.

How does the MXene@Zn-MOF–loaded microneedle system act against bacteria and biofilms?

It provides strong antibacterial inhibition against E. coli and S. aureus and enables effective removal of the bacterial biofilm covering the wound site.

Which signaling pathways are key for immune regulation and angiogenesis in this design?

The system activates the TGF-β signaling pathway to promote angiogenesis, while it suppresses the TNF-α signaling pathway to reduce inflammation and supports macrophage polarization toward the M2 phenotype.

Sep 30, 2026

Uploaded by Eliana