bims-engexo 2026-02-01 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–02–01
nineteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Enhancing osteoporosis treatment: emerging roles of engineered exosomes in bone regeneration and repair.
Exosomes displaying native EGF enhance doxorubicin's therapeutic efficacy and reduce cardiotoxicity.
Therapeutic Exosomes Carrying VEGFA siRNA Inhibit Pathological Corneal Angiogenesis via PI3K-Akt-Caspase-3 Signaling.
Optimizing Extracellular Vesicles for Cardiac Repair Post-Myocardial Infarction: Approaches and Challenges.
Drug-Loaded Extracellular Vesicle-Based Drug Delivery: Advances, Loading Strategies, Therapeutic Applications, and Clinical Challenges.
Nanotechnology-driven biomaterials for chronic liver diseases: Stage-specific strategies for advanced theranostics.
Exosomes-mediated delivery of miR-27a-3p antagomir alleviates white matter injury by regulating PPARγ/PRDX1/JNK pathway after subarachnoid hemorrhage in rats.
Sclerostin-targeted delivery of PCSK9 siRNA reverses osteoporosis in OVX mice.
Cancer-associated fibroblasts-derived exosomes in colorectal cancer progression: Mechanism and therapeutic opportunities.
A Dual-Dynamic Crosslinked Polysaccharide-Based Hydrogel Loaded with Exosomes for Promoting Diabetic Wound Healing.
Effects of Periodontal-Specific Exosomes and rhBMP2 on Osteogenic Behaviour and Differentiation of BMSCs.
Mesenchymal Stem Cell-Derived Exosomes miR-143-3p Attenuates Diabetic Kidney Disease by Enhancing Podocyte Autophagy via Bcl-2/Beclin1 Pathway.
Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease.
Engineered Biomimetic Nanorobots Orchestrate Targeted Nose-to-Brain Delivery to Resolve Neuron-Glia Entanglement against Parkinson's Disease.
SHED-exosome-functionalized degradable fibrous coatings: Immunomodulatory engineering of titanium implant interfaces.
Endothelial cell-derived exosomes inhibit high glucose-induced osteoblast ferroptosis by activating microRNA-335-3p/prostaglandin endoperoxide synthase 2.
Engineering Self-Assembled PEEK Scaffolds with Marine-Derived Exosomes and Bacteria-Targeting Aptamers for Enhanced Antibacterial Functions.
M2-Macrophage-Derived Extracellular Vesicles-Functionalized Acellular Dermal Matrix as a New-Generation Immunoregulatory and Angio-Inductive Construct for Skin Tissue Engineering.
Hypoxic stem cells from apical papilla-derived exosomes enhance dental pulp stem cells migration and differentiation via mitochondrial activation.

J Transl Med. 2026 Jan 29.

Enhancing osteoporosis treatment: emerging roles of engineered exosomes in bone regeneration and repair.

Hongtao Li, Hongyu Pan, Minshan Feng.



Keywords:  Biomedical engineering; Drug delivery systems; Exosomes; Nanotechnology; Osteoporosis

DOI:  https://doi.org/10.1186/s12967-025-07653-2
J Nanobiotechnology. 2026 Jan 27.

Exosomes displaying native EGF enhance doxorubicin's therapeutic efficacy and reduce cardiotoxicity.

Liang Mao, Longtao Qian, Xin Zhou, Keran Niu, Zelin Li, Shuyun Wang, Jiankang Xie, Wen Zhou, Xitong Dang.

   BACKGROUND: Doxorubicin (DOX) is one of the most potent chemotherapeutic agents for cancer treatment. However, its cumulative and often irreversible, life-threatening cardiotoxicity significantly limits its clinical applications. While strategies like dose reduction, iron chelation, and liposome encapsulation have aided in mitigating cardiotoxicity to certain extent, they are associated with decreased therapeutic efficacy and potential cancer relapse, the risk of developing secondary malignancy, and the incidence of the Hand-foot syndrome. Exosomes (Exo) are naturally occurring nanoparticles that can be engineered to display targeting moieties on their surface, thereby enhancing drug delivery efficacy. We aimed to develop an exosomal DOX formulation targeting broad epidermal growth factor receptor (EGFR) variants to enhance its anti-tumor efficacy and minimize cardiotoxicity.
RESULTS: The native 53-amino-acid EGF was decorated on the surface of exosomes by genetically engineering exosome-producing A549 cells. The EGF-Exo was effectively internalized by tumor cell lines in a manner dependent on EGFR expression levels, and exhibited enhanced accumulation in xenograft A549 tumors relative to the heart, with minimal cardiac accumulation. When loaded with DOX, these engineered exosomes were rapidly internalized, inducing higher apoptosis in A549 cells compared to liposomal-DOX. Upon systemic administration in an A549 xenograft mouse model, EGF-Exo-DOX exhibited enhanced accumulation in tumors relative to the heart, with minimal cardiac accumulation, significantly reducing tumor burden, mitigating DOX-induced cardiotoxicity, and exhibiting no tumorigenic effects. This favorable therapeutic profile is primarily attributed to DOX-induced apoptosis.
CONCLUSIONS: Our findings demonstrate that tumor-derived exosomes engineered with EGF on their surface enable targeted drug delivery to tumors with high EGFR expression. Although the exosomes modestly increase cell proliferation in vitro, the EGF-Exo-DOX formulation exhibits enhanced tumor accumulation relative to the heart, minimal cardiac uptake, and shows no tumorigenic effects in vivo. Compared to Lipo-DOX, a widely used clinical formulation of liposomal DOX in China, EGF-Exo-DOX demonstrates superior cellular uptake, greater induction of tumor cell apoptosis, and improved anti-tumor efficacy. These results highlight the potential of engineered exosomes as a targeted drug delivery platform for patients with EGFR-overexpressing tumors.

Keywords:  Cardiotoxicity; Doxorubicin; EGF ligand; EGFR; Exosomes; Targeted delivery

DOI:  https://doi.org/10.1186/s12951-025-04002-9
Biomedicines. 2026 Jan 21. pii: 246. [Epub ahead of print]14(1):

Therapeutic Exosomes Carrying VEGFA siRNA Inhibit Pathological Corneal Angiogenesis via PI3K-Akt-Caspase-3 Signaling.

Woojune Hur, Basanta Bhujel, Seorin Lee, Seheon Oh, Ho Seok Chung, Hun Lee, Jae Yong Kim.

  Background/Objectives: Neovascularization, defined as the sprouting of new blood vessels from pre-existing vasculature, is a critical pathological feature in ocular diseases such as pathological myopia and represents a leading cause of corneal vision loss. Vascular endothelial growth factor A (VEGFA) plays a pivotal role in endothelial cell proliferation, migration, survival by anti-apoptotic signaling, and vascular permeability. Dysregulation of VEGFA is closely linked to pathological neovascularization. Exosomes, nanosized phospholipid bilayer vesicles ranging from 30 to 150 nm, have emerged as promising gene delivery vehicles due to their intrinsic low immunogenicity, superior cellular uptake, and enhanced in vivo stability. This study aimed to investigate whether highly purified mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA labeled with FAM can effectively suppress pathological corneal neovascularization (CNV) via targeeted cellular transduction and VEGFA inhibition. Furthermore, we examined whether the therapeutic effect involves the modulation of the PI3K-Akt-Caspase-3 signaling axis. Methods: Exosomes purified by chromatography were characterized by electronmicroscopy, standard marker immunoblotting, and nanoparticle tracking analysis. In vitro, we assessed exosome uptake and cytoplasmic release, suppression of VEGFA mRNA/protein, cell viability, and apoptosis. In a mouse CNV model, we evaluated tissue reach and stromal retention after repeated intrastromal injections; anterior segment angiogenic indices; CD31/VEGFA immunofluorescence/immunoblotting; phosphorylated PI3K and Akt; cleaved caspase-3; histology (H&E); and systemic safety (liver, kidney, and spleen). Results: Exosomes were of high quality and showed peak efficacy at 48 h, with decreased VEGFA mRNA/protein, reduced viability, and increased apoptosis in vitro. In vivo, efficient delivery and stromal retention were observed, with accelerated inhibition of neovascularization after Day 14 and maximal effect on Days 17-19. Treatment reduced CD31 and VEGFA, decreased p-PI3K and p-Akt, and increased cleaved caspase-3. Histologically, concurrent reductions in neovascularization, inflammatory cell infiltration, and inflammatory epithelial thickening were observed, alongside a favorable systemic safety profile. Conclusions:VEGFA siRNA-loaded exosomes effectively reduce pathological CNV via a causal sequence of intracellular uptake, cytoplasmic release, targeted inhibition, and phenotypic suppression. Supported by consistent PI3K-Akt inhibition and caspase-3-mediated apoptosis induction, these exosomes represent a promising local gene therapy that can complement existing antibody-based treatments.

Keywords:  VEGFA; anti-angiogenesis; apoptosis; caspase-3; corneal neovascularization; exosomes; gene therapy; mesenchymal stem cell (MSC); phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway

DOI:  https://doi.org/10.3390/biomedicines14010246
Biomolecules. 2025 Dec 30. pii: 58. [Epub ahead of print]16(1):

Optimizing Extracellular Vesicles for Cardiac Repair Post-Myocardial Infarction: Approaches and Challenges.

Yanling Huang, Han Li, Jinjie Xiong, Xvehua Wang, Jiaxi Lv, Ni Xiong, Qianyi Liu, Lihui Yin, Zhaohui Wang, Yan Wang.

  Ischemic heart disease remains the leading cause of cardiovascular mortality worldwide. In myocardial infarction (MI), extracellular vesicles (EVs)-particularly small EVs (sEVs)-transport therapeutic cargo such as miR-21-5p, which suppresses apoptosis, and other proteins, lipids, and RNAs that can modulate cell death, inflammation, angiogenesis, and remodeling. This review synthesizes recent mechanistic and preclinical evidence on native and engineered EVs for post-MI repair, mapping therapeutic entry points across the MI timeline (acute injury, inflammation, and healing) and comparing EV sources (stem-cell and non-stem-cell), administration routes, and dosing strategies. We highlight engineering approaches-including surface ligands for cardiac homing, rational cargo loading to enhance potency, and biomaterial depots to prolong myocardial residence-that aim to improve tropism, durability, and efficacy. Manufacturing and analytical considerations are discussed in the context of contemporary guidance, with emphasis on identity, purity, and potency assays, as well as safety, immunogenicity, and pharmacology relevant to cardiac populations. Across small- and large-animal models, EV-based interventions have been associated with reduced infarct/scar burden, enhanced vascularization, and improved ventricular function, with representative preclinical studies reporting approximately 25-45% relative reductions in infarct size in rodent and porcine MI models, despite substantial heterogeneity in EV sources, formulations, and outcome reporting that limits cross-study comparability. We conclude that achieving clinical translation will require standardized cardiac-targeting strategies, validated good manufacturing practice (GMP)-compatible manufacturing platforms, and harmonized potency assays, alongside rigorous, head-to-head preclinical designs, to advance EV-based cardiorepair toward clinical testing.

Keywords:  EVs; cardiac repair; engineered exosomes; extracellular vesicles (EVs); ischemia–reperfusion (I/R) injury; myocardial infarction (MI); targeted delivery

DOI:  https://doi.org/10.3390/biom16010058
Pharmaceutics. 2025 Dec 29. pii: 45. [Epub ahead of print]18(1):

Drug-Loaded Extracellular Vesicle-Based Drug Delivery: Advances, Loading Strategies, Therapeutic Applications, and Clinical Challenges.

Linh Le Dieu, Adrienn Kazsoki, Romána Zelkó.

  Background/Objectives: Extracellular vesicles (EVs) are nanosized carriers with high biocompatibility, low immunogenicity, and the ability to cross biological barriers, making them attractive for drug delivery. Despite growing interest, the clinical translation of drug-loaded EVs remains limited. This systematic review aimed to summarize current evidence on EV sources, loading strategies, therapeutic applications, and translational challenges. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in Embase, PubMed, Reaxys, and Scopus for the period 2020-2025. Eligible studies included original articles on drug-loaded EVs from human, animal, plant, or other sources. Data on EV source, drug type, particle size, loading method, administration route, and therapeutic application were extracted. Clinical trials were identified through ClinicalTrials.gov. Results: A total of 65 studies were included after screening 5316 records, along with two clinical trials. Human mesenchymal stem cell (MSC)-derived EVs were the most frequent source in oncology, while plant-derived EVs predominated in non-oncology applications. Anti-cancer drugs such as doxorubicin, gemcitabine, and docetaxel were most frequently loaded, alongside curcumin, berberine, and atorvastatin. EV sizes generally ranged from 50 to 200 nm, with larger vesicles reported for plant-derived EVs. Intravenous administration predominated, with most studies demonstrating sustained release and enhanced therapeutic efficacy. Passive loading was most common, especially for hydrophobic drugs, whereas active methods such as electroporation and sonication were preferred for hydrophilic cargo. Two clinical trials showed preliminary therapeutic benefits with favorable safety. Conclusions: Drug-loaded EVs represent a promising and versatile drug delivery platform, yet their clinical translation is hindered by variability in isolation and loading methods, production scalability, and safety evaluation. Further standardization and large-scale studies are needed to advance EV-based therapeutics toward clinical use.

Keywords:  clinical translation; drug delivery system; exosomes; extracellular vesicles; loading strategies; nanomedicine; therapeutic application

DOI:  https://doi.org/10.3390/pharmaceutics18010045
Acta Biomater. 2026 Jan 24. pii: S1742-7061(26)00059-0. [Epub ahead of print]

Nanotechnology-driven biomaterials for chronic liver diseases: Stage-specific strategies for advanced theranostics.

Yishui Cai, Tianqi Nie, Xi Luo, Yiqun Wu, Jun Wu.

  Chronic liver diseases (CLDs), encompassing a spectrum from steatosis and inflammation to fibrosis, cirrhosis, represent a major global health burden, causing approximately 2 million deaths annually [1]. The management of CLDs is significantly hampered by the limitations of conventional approaches, including non-targeted drug delivery, systemic toxicity, and inadequate diagnostic sensitivity for early-stage lesions. Nanotechnology-driven biomaterial platforms have emerged as pioneering solutions to these challenges, enabling precise theranostic strategies tailored to the distinct pathophysiology of each disease stage. This review systematically elaborates on these advancements by aligning with the natural progression of CLDs [non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and cirrhosis]. We detail how engineered platforms enhance therapeutic efficacy by achieving superior hepatic accumulation, controlled drug release, and improved metabolic, antiviral, and antifibrotic effects. Concurrently, we explore their role in diagnostics, where nanotechnology-enhanced imaging agents and nanosensors provide unprecedented sensitivity for early detection and accurate staging. By structuring the discussion around the evolving clinical needs from NAFLD and hepatitis to advanced fibrosis and cirrhosis, this review offers a stage-specific roadmap of biomaterial design principles. It aims to provide a foundational theory and forward-looking perspectives for developing next-generation, precision medicine solutions for CLDs, ultimately bridging the gap between benchtop innovation and clinical translation. STATEMENT OF SIGNIFICANCE: This review establishes a stage-specific design paradigm that bridges the gap between biomaterial innovation and the clinical continuum of chronic liver diseases (CLDs). Its significance lies in aligning cutting-edge biomaterial strategies from targeted, stimuli-responsive nanotherapeutics to engineered exosomes and gene delivery systems with the distinct pathophysiological features of each disease stage. This approach moves beyond cataloging materials to critically evaluating their translational feasibility. We analyze how rational material design addresses specific clinical bottlenecks, such as improving drug bioavailability to diseased tissue or enabling sensitive, non-invasive diagnostics for early detection. By providing this clinically focused roadmap, this review aims to accelerate the development of personalized therapies and reshape the theranostic landscape, striving to improve therapeutic outcomes of CLDs.

Keywords:  Biomaterials; Chronic Liver diseases; Diagnosis; Drug delivery; Theranostics

DOI:  https://doi.org/10.1016/j.actbio.2026.01.043
Exp Neurol. 2026 Jan 23. pii: S0014-4886(26)00030-0. [Epub ahead of print] 115667

Exosomes-mediated delivery of miR-27a-3p antagomir alleviates white matter injury by regulating PPARγ/PRDX1/JNK pathway after subarachnoid hemorrhage in rats.

Zhaosi Zhang, Fuming Liang, Daochen Wen, Hong Chen, Nina Gu, Zhao Li, Lin Wang, Yingwen Wang, Qiuling Pan, Yajun Zhu, Dan Xu, Xiaochuan Sun, Chongjie Cheng, Jin Yan.

  White matter injury (WMI) is a critical factor contributing to poor neurological outcomes following subarachnoid hemorrhage (SAH). MicroRNAs (miRNAs) are key regulators of WMI-related pathology and can be delivered via exosomes, yet their mechanisms and therapeutic potential remain largely unexplored. In this study, miRNA sequencing revealed a significant upregulation of miR-27a-3p in peripheral blood exosomes after SAH, which was further confirmed in white matter tissue. BV2 cell-derived exosomes loaded with miR-27a-3p antagomir were administered intranasally and effectively targeted oligodendrocytes. Treatment with these exosomes alleviated WMI by reducing oligodendrocyte apoptosis and promoting the proliferation and differentiation of oligodendrocyte precursor cells, leading to improved neurological and electrophysiological recovery. Mechanistically, miR-27a-3p inhibited PPARγ, resulting in downregulation of PRDX1 and activation of the JNK pathway, which triggered oligodendrocyte apoptosis. These findings demonstrate that exosome-mediated delivery of miR-27a-3p antagomir mitigates SAH-induced WMI through modulation of the PPARγ/PRDX1/JNK axis, providing a promising noninvasive therapeutic approach for enhancing white matter repair and functional recovery after SAH.

Keywords:  Exosome; Subarachnoid hemorrhage; White matter injury; miR-27a-3p

DOI:  https://doi.org/10.1016/j.expneurol.2026.115667
Bone. 2026 Jan 27. pii: S8756-3282(26)00034-7. [Epub ahead of print] 117808

Sclerostin-targeted delivery of PCSK9 siRNA reverses osteoporosis in OVX mice.

Hongling Wu, Liyuan Huang, Fangfang Song, Yueli Zhou, Yanru Wu, Jiqi Zheng, Zhengrong Yin, Yanyang Wei, Hualing Sun, Cui Huang.

  The role of PCSK9 in bone metabolism has recently emerged as a critical area of research. This study identifies a significant upregulation of PCSK9, approximately 1.2-fold in ovariectomized (OVX) mice serum, approximately 3-fold in OVX mice bone marrow stem cells, which correlates strongly with decreased bone mineral density, implicating PCSK9 in estrogen deficiency-induced bone loss. Genetic knockout of PCSK9 was found to ameliorate osteoporosis by improving bone microarchitecture, increasing trabecular bone volume fraction (BV/TV) by 50%, enhancing bone formation (serum PINP increased by 30%), and bone resorption (serum β-CTX increased by 10%), confirming its dual regulatory function. Based on these findings, we engineered a bone-targeted exosome delivery system by surface functionalizing exosomes with an anti-sclerostin (anti-SCL) fragment. This novel system facilitated efficient bone-specific enrichment (fluorescence intensity in bone increased by 60%) and the successful delivery of siPCSK9, resulting in potent silencing of bone marrow PCSK9 expression. In OVX osteoporotic mice, this targeted intervention markedly attenuated bone loss. A 2-fold increase in bone mass was observed relative to the untreated OVX group. Our work not only elucidates a pivotal role of PCSK9 in osteoporosis pathogenesis but also provides a compelling proof-of-concept for exosome-based precision therapy, offering substantial potential for clinical translation.

Keywords:  Bone metabolism; Osteoporosis; PCSK9; Sclerostin-targeted exosomes; siRNA

DOI:  https://doi.org/10.1016/j.bone.2026.117808
Biochim Biophys Acta Rev Cancer. 2026 Jan 27. pii: S0304-419X(26)00017-X. [Epub ahead of print] 189545

Cancer-associated fibroblasts-derived exosomes in colorectal cancer progression: Mechanism and therapeutic opportunities.

Linling Yang, Parastoo Akbarabadi, Sadegh Babashah.

  Colorectal cancer (CRC) progression is profoundly shaped by the tumor microenvironment. Among stromal components, cancer-associated fibroblasts (CAFs) release small extracellular vesicles (exosomes) that deliver miRNAs, lncRNAs, circRNAs, proteins, and metabolites to malignant and immune cells. In CRC, CAF-derived exosomes (CAF-Exo) drive epithelial-mesenchymal transition, sustain stemness, stimulate angiogenesis, suppress antitumor immunity, and promote resistance to fluoropyrimidines and oxaliplatin. Representative mechanisms include exosomal miR-92a-3p activation of Wnt/β-catenin signaling, the lncRNA WEE2-AS1-mediated suppression of Hippo restraint with YAP activation, and circRNA cargos that reprogram autophagy or endothelial dynamics. Circulating CAF-Exo signatures are emerging as minimally invasive biomarkers for diagnosis, prognosis, and therapy stratification. However, translation remains limited by CAF heterogeneity, cargo variability, and incomplete in vivo characterization of vesicle dynamics. Therapeutic opportunities include blockade of exosome biogenesis or uptake, pharmacologic reprogramming of CAFs, and engineering vesicles to deliver targeted inhibitors or RNA-based therapeutics. This review synthesizes current mechanistic insights, evaluates biomarker potential, and outlines clinical priorities for targeting CAF-exosomal pathways in CRC.

Keywords:  Biomarkers; Cancer-associated fibroblasts; Colorectal cancer; Exosomes; Non-coding RNAs; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.bbcan.2026.189545
Materials (Basel). 2026 Jan 22. pii: 445. [Epub ahead of print]19(2):

A Dual-Dynamic Crosslinked Polysaccharide-Based Hydrogel Loaded with Exosomes for Promoting Diabetic Wound Healing.

Ding Lin, Zhenhao Li, Jianying Hao, Xiaobo Xu, Xiuqiang Li, Yuan Feng, Xiaochen Lu, Fanglian Yao, Hong Zhang, Junjie Li.

  Diabetic wounds are often accompanied by severe inflammation, which is unfavorable for vascular growth and wound repair. Therefore, promoting the healing of diabetic wounds is of great significance. In this study, carboxymethyl chitosan (CMCS) was grafted with 4-formylphenylboronic acid (FPBA) and then crosslinked with oxidized sodium alginate (OAlg) to form a dual-dynamic covalent hydrogel (CPOA) based on borate ester bond and Schiff base bonds. Mesenchymal stem cells' exosomes (Exos) were incorporated into the CPOA to construct CPOA@Exos for diabetic wound healing. Owing to the dual-dynamic covalent crosslinking network, the CPOA hydrogel showed good injectability and self-healing ability. In addition, the hydrogel displayed reactive oxygen species (ROS) responsive properties, enabling both scavenging of multiple free radicals and on-demand release of Exos in the ROS-rich wound microenvironment. A diabetic wound model was established on C57 mice, and treatment with CPOA@Exos demonstrated that it could promote the polarization of macrophages toward the M2 phenotype, enhance cellular proliferation in the wounded area, and thereby accelerate the healing of diabetic wounds. In conclusion, this study provides a new hydrogel wound dressing that can inhibit inflammation for the management of diabetic wounds.

Keywords:  diabetic wound; exosomes; hydrogel; reactive oxygen species (ROS)

DOI:  https://doi.org/10.3390/ma19020445
J Cell Mol Med. 2026 Feb;30(3): e71039

Effects of Periodontal-Specific Exosomes and rhBMP2 on Osteogenic Behaviour and Differentiation of BMSCs.

Paras Ahmad, Danyal A Siddiqui, Jared Bianchi-Smak, Nima Farshidfar, Nathan Estrin, Richard J Miron, Georgios A Kotsakis.

  Growth factors, including recombinant human bone morphogenetic protein-2 (rhBMP2), have been clinically utilised for large bone augmentation with good outcomes. Nevertheless, long-term healing, swelling, safety concerns, and high cost limit their use. Exosomes, nanoscale extracellular vesicles, have emerged as promising regenerative alternatives. This study assessed the osteogenic potential of periodontal-specific exosomes (Px) on bone marrow mesenchymal stem cells (BMSCs) compared to rhBMP2. Px were morphologically characterised by TEM and quantified via BCA assay. BMSCs were treated with Px at 1:10, 1:50, and 1:100 dilutions (100, 20, and 10 μg/mL) and compared to rhBMP2 (100 ng/mL). Px uptake was evaluated using PKH26 labeling. Functional assays included viability, migration, alkaline phosphatase (ALP) activity, alizarin red (ARS) mineralization, collagen, osteocalcin secretion, and RT-PCR analysis of osteogenic genes. Px exhibited spheroidal to cup-shaped morphology and internalisation in BMSCs up to 18 days. Compared to rhBMP2, Px promoted viability (1.14-fold), migration (1.78-fold) up to 1.14 and 1.78-fold, ALP (1.48-, 4.11-fold), ARS (1.43-, 14.71-fold), collagen (1.40-, 3.58-fold), and osteocalcin (1.86-, 5.2-fold). Gene expression demonstrated significant upregulation of ALP (1.73-fold), RUNX2 (1.70-fold), OCN (1.36-fold), and OPN (1.35-fold). Overall, Px significantly enhanced BMSC osteogenesis compared to rhBMP2, highlighting their potential as a cell-free nanotherapeutic in bone tissue engineering.

Keywords:  amniotic fluid; bone marrow cells; bone morphogenetic protein 2; exosomes; mesenchymal stem cells

DOI:  https://doi.org/10.1111/jcmm.71039
Biomedicines. 2026 Jan 14. pii: 184. [Epub ahead of print]14(1):

Mesenchymal Stem Cell-Derived Exosomes miR-143-3p Attenuates Diabetic Kidney Disease by Enhancing Podocyte Autophagy via Bcl-2/Beclin1 Pathway.

Wenze Song, Jiao Wang, Lulu Guan, Yun Zou, Jiarong Liu, Wen Chen, Jixiong Xu, Wei Cai.

  Objective: Diabetic kidney disease (DKD) is characterized by podocyte injury and impaired autophagy. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) exhibit therapeutic potential for DKD, yet their mechanisms remain unclear. This study investigated whether BMSC-Exos restore podocyte autophagy via the miR-143-3p/Bcl-2/Beclin1 axis to delay DKD progression. Methods: A high-glucose (HG)-induced podocyte injury model was established using mouse podocytes (MPC5). Autophagy-related proteins (Beclin1, Bcl-2, LC3) and the injury marker desmin were analyzed by Western blot and immunofluorescence (IF). High-throughput sequencing identified BMSC-Exos-enriched miRNAs, with the miR-143-3p/Bcl-2 targeting relationship validated by dual-luciferase reporter assays. BMSCs transfected with miR-143-3p mimic or inhibitor were used to assess exosomes effects on autophagy and podocin expression. In vivo, DKD mice received tail vein injections of modified BMSC-Exos, followed by evaluation of physiological parameters, biochemical indices, and renal histopathology. Results: BMSC-Exos were successfully isolated and characterized. Fluorescence microscopy confirmed exosomes internalization by HG-treated MPC5 cells. BMSC-Exos upregulated Beclin1 and LC3-II while downregulating Bcl-2 and desmin, indicating enhanced autophagy. High-throughput sequencing revealed miR-143-3p enrichment in BMSC-Exos, and Bcl-2 was confirmed as a direct target of miR-143-3p. Exosomes from miR-143-3p mimic-transfected BMSCs further promoted autophagy and podocin expression. In DKD mice, BMSC-Exos reduced blood glucose, urinary albumin-to-creatinine ratio (UACR), and ameliorated renal damage, whereas miR-143-3p inhibition attenuated these effects. Conclusions: BMSC-Exos deliver miR-143-3p to target Bcl-2, thereby activating Beclin1-mediated autophagy and ameliorating DKD. This study elucidates a novel autophagy regulatory mechanism supporting BMSC-Exos as a cell-free therapy for DKD.

Keywords:  autophagy; diabetic kidney disease; exosome; mesenchymal stem cells; podocyte

DOI:  https://doi.org/10.3390/biomedicines14010184
Pharmaceutics. 2026 Jan 16. pii: 116. [Epub ahead of print]18(1):

Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Yu Lei, Mei Liu, Xiang Tao.

  Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a multifaceted systemic condition, with the mechanisms linking intrahepatic lesions to systemic complications remaining a significant enigma in the field. This review posits that extracellular vesicles (EVs) serve as pivotal mediators facilitating communication between the liver and the entire organism. Within the hepatic environment, lipotoxic hepatocyte-derived EVs modulate macrophage populations and stellate cells, thereby promoting inflammatory and fibrotic processes. Systemically, the liver engages in bidirectional communication with adipose tissue, the intestinal tract, the cardiovascular system, and the pancreas via EVs, thus orchestrating metabolic homeostasis. Furthermore, we critically evaluate non-invasive diagnostic strategies and emerging therapies, including both natural and engineered EVs, based on EV-based interventions. We highlight the substantial potential and current challenges associated with achieving precision medicine in MASLD through targeted modulation of this specific communication network.

Keywords:  diagnostics; extracellular vesicles; metabolic dysfunction-associated steatotic liver disease; treatment

DOI:  https://doi.org/10.3390/pharmaceutics18010116
Small. 2026 Jan 29. e13394

Engineered Biomimetic Nanorobots Orchestrate Targeted Nose-to-Brain Delivery to Resolve Neuron-Glia Entanglement against Parkinson's Disease.

Yang Xu, Jing-Yu Zhao, Xi-Yuan Xu, Yu-Da Liu, Yu-Wen Li, Li-Hua Peng.

  Intranasal administration enables direct brain drug delivery, showing promise for Parkinson's disease (PD) treatment. However, nose-to-brain delivery confronts sequential obstacles, including mucosal penetration, lesion-specific accumulation, and active targeting toward disease-relevant cells, demanding advanced nanotherapeutic design. Meanwhile, neural mitochondrial dysfunction and neuroinflammation constitutes two cross-interfering pathogeneses that drive PD progression. Herein, we developed an intelligent biomimetic nanoplatform (hPH‑RNPEC) based on Pueraria lobata-derived exosomes. The system is engineered with neutrophil-like membrane for inflammatory tropism, spatially staggered short unit of rabies virus glycoprotein (RVG) peptide for neuron-microglia dual targeting, and long motif of the tetrablock conjugation of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), pH-sensitive hydrazone bond, polyethylene glycol 2000 (PEG2k), and a histidine-switching peptide for efficient nasal mucosal penetration. Spatiotemporally, following intranasal administration in PD mice, hPH‑RNPEC can penetrate nasal mucosa, achieve inflammation‑directed lesion accumulation, and realize efficient cellular internalization. The system also co‑delivers endogenous exosomal miRNAs and therapeutic curcumin to mitigate neural mitochondrial damage and neuroinflammation collectively evidenced by mitochondrial function and inflammation assessment. Besides, single-cell RNA sequencing (scRNA-seq) further suggested the promotion of myelin repair and rewiring of neural circuits, which facilitate the remodeling of PD microenvironment. This study establishes an engineered biomimetic nanorobot platform for precise brain targeting and multifactorial intervention for PD treatment.

Keywords:  Parkinson's disease; exosome‐based biomimetic nanorobot; remodeled neuron‐glia network; spatiotemporal nose‐to‐brain delivery

DOI:  https://doi.org/10.1002/smll.202513394
Colloids Surf B Biointerfaces. 2026 Jan 27. pii: S0927-7765(26)00067-6. [Epub ahead of print]262 115479

SHED-exosome-functionalized degradable fibrous coatings: Immunomodulatory engineering of titanium implant interfaces.

Rui Wang, Yicheng Cheng, Hong Chen, Wenxi Shan, Youbei Qiao, Jiang Wu.

  The host immune response critically determines the regeneration efficacy of peri-implant tissues. Exosomes derived from stem cells from human exfoliated deciduous teeth (SHED-Exo), enriched with bioactive components, demonstrate proven immunomodulatory capabilities. This study developed a composite structured coating system for loading and sustained-release delivery of SHED-Exo on titanium implants. The system integrates chitosan nanoparticles (CS-NPs) encapsulating SHED-Exo (CS@Exo NPs) within a Polylactic acid/polymalic acid (PLA/PMLA) electrospun nanofibrous membrane. Key findings revealed that: (1) CS-NPs maintained structural integrity and bioactivity of encapsulated SHED-Exo, enabling effective cellular internalization; (2) The composite coating comprising nanofibers and nanoparticles (PLA/PMLA/CS@Exo) demonstrated superior sustained-release performance, achieving continuous exosome delivery for over 30 days; (3) Released exosomes significantly promoted macrophage M2 polarization and anti-inflammatory cytokine secretion in vitro; (4) The nanofibrous coating exhibited excellent mechanical stability during simulated implantation and degradation characteristics. This dual nanoarchitecture establishes a robust platform for implant-surface functionalization, combining immunomodulation through bioactive exosome delivery with favorable degradation profiles.

Keywords:  Electrospinning; Exosomes; Macrophages; Nanoparticles; Polymalic acid

DOI:  https://doi.org/10.1016/j.colsurfb.2026.115479
World J Diabetes. 2026 Jan 15. 17(1): 111165

Endothelial cell-derived exosomes inhibit high glucose-induced osteoblast ferroptosis by activating microRNA-335-3p/prostaglandin endoperoxide synthase 2.

Chen Shao, Li-Jian Zhang, Yi-Lin Song, Yan-Qiu Wang, Xiu-Jing Zha, Juan Li, Cheng-Song Ye, Ling-Ling Chen, Ming-Wei Chen, Guo-Xi Jin.

   BACKGROUND: Diabetic osteoporosis (DOP), a serious complication of type 2 diabetes mellitus (T2DM), involves ferroptosis-mediated disruption of bone metabolism. While endothelial cell-derived exosomes (EC-Exos) demonstrate inherent bone-targeting properties, their role in counteracting high glucose (HG)-induced osteoblast ferroptosis remains unexplored.
AIM: To investigate whether EC-Exos protect against HG-induced osteoblast ferroptosis through microRNA (miR)-335-3p-mediated regulation of prostaglandin endoperoxide synthase 2 (PTGS2) and evaluate clinical relevance in DOP.
METHODS: Mouse vascular endothelial cells (bEND.3) and osteoblasts (MC3T3E1) were used. Exosomes were isolated and subsequently characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting for CD63 and CD81. miR expression profiles were compared between HG-treated osteoblasts and exosome-cocultured groups using high-throughput sequencing and quantitative reverse transcription polymerase chain reaction. Targeting of PTGS2 mRNA by miR-335-3p was validated by dual-luciferase reporter assay. Ferroptosis markers, reactive oxygen species, malondialdehyde, glutathione (GSH), PTGS2, GSH peroxidase 4, solute carrier family 7 member 11, and solute carrier family 3 member 2, were quantified following miR-335-3p inhibition. Serum samples from 30 T2DM patients and 32 DOP patients were analyzed. miR-335-3p levels were measured by quantitative reverse transcription polymerase chain reaction, and PTGS2 concentrations were determined via enzyme-linked immunosorbent assay. Diagnostic performance was assessed using receiver operating characteristic curves and logistic regression.
RESULTS: EC-Exos significantly reduced reactive oxygen species levels and malondialdehyde, while increasing GSH in HG-treated osteoblasts. miR-335-3p expression increased 3.7-fold in exosome-treated cells vs HG controls. miR-335-3p directly bound the PTGS2 3' untranslated region. Inhibition of miR-335-3p abolished exosomal protection against ferroptosis, as demonstrated by increased PTGS2 expression and reduced levels of GSH peroxidase 4, solute carrier family 7 member 11, and solute carrier family 3 member 2. DOP patients exhibited lower serum miR-335-3p and higher PTGS2 compared with T2DM controls, showing a strong inverse correlation. miR-335-3p demonstrated diagnostic potential for DOP.
CONCLUSION: EC-Exos affect ferroptosis in osteoblasts induced by HG by activating miR-335-3p/PTGS2. Serum miR-335-3p may be a novel diagnostic biomarker.

Keywords:  Exosomes; Ferroptosis; Osteoporosis; Oxidative stress; Type 2 diabetes

DOI:  https://doi.org/10.4239/wjd.v17.i1.111165
J Funct Biomater. 2025 Dec 30. pii: 23. [Epub ahead of print]17(1):

Engineering Self-Assembled PEEK Scaffolds with Marine-Derived Exosomes and Bacteria-Targeting Aptamers for Enhanced Antibacterial Functions.

Chen Zhang, Jinchao You, Runyi Lin, Yuansong Ye, Chuchu Cheng, Haopeng Wang, Dejing Li, Junxiang Wang, Shan Chen.

  Repairing bone defects with implants is an important topic in the field of regenerative medicine, but bacterial infection presents a significant barrier in clinical practice. Therefore, bone implants with antibacterial functionality are currently in high demand. Fresh seaweed-derived exosomes (EXOs) exhibited promising antibacterial activity against bacteria, indicating their potential as natural antimicrobial agents. Moreover, equipping the exosomal lipid bilayer with bacteria-targeting aptamers (Apt), termed EXOs-Apt, enabled precise bacterial killing, thereby promoting more effective antibacterial functions. In our design, porous polyetheretherketone (PEEK) scaffolds were 3D-printed using the melt deposition manufacturing process. Subsequently, the scaffold surfaces were modified via dopamine self-polymerization, resulting in the formation of a polydopamine (PDA) coating. Then, EXOs-Apt was applied to functionalize PEEK scaffolds with antibacterial activity. Given that EXOs display bactericidal effects while Apt facilitates bacterial capture, we engineered a surface coating platform that incorporates both components to produce a multifunctional scaffold with synergistic antibacterial activity. The results showed that modifying EXOs-Apt on PEEK scaffolds significantly improved their antibacterial performance against Escherichia coli and Staphylococcus aureus. To our knowledge, this is the first study to use EXOs-Apt as antibacterial coatings modified on PEEK scaffolds. This study provides new strategies and ideas for the development of antibacterial PEEK orthopedic implants with promising clinical value for infection-resistant repair of bone defects.

Keywords:  3D printing; PEEK scaffold; antibacterial; aptamer; marine-derived exosome

DOI:  https://doi.org/10.3390/jfb17010023
Macromol Biosci. 2026 Jan;26(1): e00500

M2-Macrophage-Derived Extracellular Vesicles-Functionalized Acellular Dermal Matrix as a New-Generation Immunoregulatory and Angio-Inductive Construct for Skin Tissue Engineering.

Sevval Yazicioglu, Tugba Sezgin Arslan, Yasar Kemal Erdoğan, Batur Ercan, Yavuz Emre Arslan, Burak Derkus.

  Extracellular vesicles, e.g., exosomes, derived from anti-inflammatory M2 macrophages have emerged as potent mediators of tissue regeneration through their ability to modulate cellular behavior, immune responses, and angiogenesis. In this study, we developed a composite bioactive scaffold by integrating M2 macrophage-derived EVs (M2-EVs) into decellularized skin extracellular matrix (dSECM), and systematically evaluated its structural, biochemical, and regenerative properties. Bovine dermis was decellularized using chemical, enzymatic, and physical steps, yielding collagen-rich, DNA-depleted ECM matrices with preserved collagen content and tunable stiffness (15-40 kPa). M2-EVs were isolated from IL-10-polarized RAW264.7 macrophages and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS, mean diameter ∼151 nm), and Western blotting for CD81/CD63/TSG101/Calnexin expressions. Functional assays revealed that M2-EVs enhanced the proliferation and migration of human dermal fibroblasts and keratinocytes, with 100 µg/mL achieving >90% wound closure at 48 h. When combined with dSECM, M2-EVs further increased the expression of immunoregulatory genes such as TGF-β (∼2.9-fold) and IL-10 (∼3.8-fold), consistent with the scaffold's capacity to enhance anti-inflammatory signaling. In the chick CAM model, dSECM/M2-EVs significantly enhanced vascularization along with increased collagen deposition and vascular smooth muscle cell recruitment. These results highlight M2-EVs as emerging biological effectors when incorporated into ECM-based scaffolds for vascularized tissue repair.

Keywords:  decellularization; extracellular matrix; extracellular vesicles; macrophage; skin tissue engineering

DOI:  https://doi.org/10.1002/mabi.202500500
J Dent Sci. 2026 Jan;21(1): 67-77

Hypoxic stem cells from apical papilla-derived exosomes enhance dental pulp stem cells migration and differentiation via mitochondrial activation.

Deyan Yuan, Rui Tao, Bi Yin, Meng Gu.

   Background/purpose: Stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) play critical roles in dental tissue regeneration. Although intercellular communication through exosomes is known to influence stem cell regulation, the effects of exosomes derived from hypoxic SCAPs on the migration and odontogenic differentiation of DPSCs have not been elucidated. This study aimed to investigate SCAPs derived exosomes mediated modulation of DPSCs biological functions under hypoxic conditions.
Materials and methods: Exosomes were obtained from SCAPs cultured under normoxic or hypoxic conditions. DPSCs were treated with these exosomes, and their migration capacity was evaluated using scratch and transwell assays. Odontogenic differentiation was assessed via gene/protein expression analysis and alizarin red / alkaline phosphatase (ALP) staining. Mitochondrial dynamics and energy metabolism were analyzed using transmission electron microscopy, seahorse assays, and Mitotracker red staining.
Results: Hypoxic SCAPs-derived exosomes exhibited comparable morphology and size to normoxic exosomes but enhanced DPSCs migration and odontogenic differentiation. Hypo-Exo promoted mitochondrial fusion in DPSCs, evidenced by increased mitofusin 2 (MFN2) / translocator of the outer mitochondrial membrane 20 (TOM20) expression and augmented mitochondrial oxygen consumption rates. Rotenone inhibition of mitochondrial metabolism abrogated Hypo-Exo-induced migration and differentiation, confirming the critical role of mitochondrial fusionmediated energy metabolism in this process.
Conclusion: Hypoxic SCAPs-derived exosomes enhance DPSCs migration and odontogenic differentiation through mitochondrial fusion. These findings reveal a novel "exosome-mitochondria" regulatory axis, providing a mechanistic basis for developing hypoxia-engineered exosome therapies in dental regenerative medicine.

Keywords:  Dental pulp stem cells (DPSCs); Exosomes; Stem cells from the apical papilla (SCAPs)

DOI:  https://doi.org/10.1016/j.jds.2025.07.028