bims-engexo 2026-05-03 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–05–03
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineered exosomes for diabetic foot ulcers: lessons learned, challenges remain.
Targeted Delivery of Engineered Exosomes and the Advances for Their Applications in Ocular Tissue.
Engineered exosome biomedical technologies for precision diagnosis and therapy in orthopedic diseases.
Carbomol hydrogels integrating chlorogenic acid-loaded exosomes promote diabetic wound healing through antibacterial and immunomodulatory activities.
Additive-Manufactured S53P4@PCL Composite Scaffolds Functionalized with Aptamers and Antibacterial Exosomes for Rapid Bacterial Capture and Killing.
Bioengineering Applications of Chinese Herbal Medicine-Derived Exosomes in Cardiovascular Diseases: Mechanisms and Translational Prospects.
Development of CAR Exosomes Targeting FAP for the Treatment of Intrauterine Adhesion.
NIR-Activated ICG-Loaded M2 Macrophage Exosomes Ameliorate Periodontitis via Targeting Infection Inflammation and Oxidative Stress.
Remote Mobilization of Gut Tregs Exosomes serves as Nanoshuttles for Targeted Cardioprotection Against Ischemia/Reperfusion Injury by Ginseng Polysaccharides.
A spatiotemporal selective bioinspired hybrid system engineered for preventing post-thrombolysis recurrence by inhibiting the ferroptosis pathway and reprogramming macrophages.
Targeted Biomimetic Stem Cell Membrane-Exosome Composite Delivery System for the Treatment of Bone Defects.
Apoptotic Vesicle Membrane-Mediated Targeted Endothelial Mitochondrial Transplantation-Clearance Therapy for Diabetic Wound Healing.
Extracellular Vesicles in Osteoarthritis: From Pathogenic Mediators to Engineered Therapeutics in a Precision Medicine Roadmap.

Mil Med Res. 2026 ;13(1): 100022

Engineered exosomes for diabetic foot ulcers: lessons learned, challenges remain.

Hyun-Do Jung.



Keywords:  Diabetic foot ulcers; Exosomes; Stimuli-responsive hydrogel; Trace element

DOI:  https://doi.org/10.1016/j.mmr.2026.100022
Curr Eye Res. 2026 Apr 29. 1-20

Targeted Delivery of Engineered Exosomes and the Advances for Their Applications in Ocular Tissue.

Ju Zhang, Yurong Shi, Linghan Gao, Wenxuan Duan, Yang Liu.

  Exosomes, a type of nanoscale vesicle produced by cells, are highly biocompatible and immunogenic. They play a crucial role in cell-to-cell communication, which contain proteins, ribonucleic acid, and other materials that can be transported to the receipt cells. Exosomes possess significant potentials as diagnostic indicators for disorders and as delivery systems for tailored therapeutics. They also exhibit distinct distributions in the eye, contributing to the regulation of both physiological and pathological processes, and are intricately linked to the onset and progression of ocular diseases. Based on the distinctive anatomical characteristics of the eye, utilization of exosomes to deliver drugs in treating the ocular diseases has shown promising prospects. However, owing to the inadequate delivery efficacy of unmodified exosomes, they need to be tailored to be more effective. In this review, we provide a brief overview of the exosome distribution in the eye and their functions in the onset and progression of the ocular diseases as well as exosome-based therapies. A large portion of this review describes the methods of exosome cargo loading, targeted modifications and their applications in treating ocular diseases. The advancements of this field are anticipated to yield a considerable therapeutic impacts, markedly enhancing the probability of visual restoration.

Keywords:  Exosome; delivery; eye; modification; ocular disease

DOI:  https://doi.org/10.1080/02713683.2026.2659098
Front Med (Lausanne). 2026 ;13 1788658

Engineered exosome biomedical technologies for precision diagnosis and therapy in orthopedic diseases.

Yuansheng Wu, Ruixuan Ma, Hongjiang Jiang.

  With population aging and sports-related injuries on the rise, the incidence of osteoarthritis, osteoporotic fractures, nonunion bone defects, and bone tumors continues to increase, while conventional pharmacologic and surgical interventions face limitations in target specificity, safety, and cost-effectiveness. Extracellular vesicles, particularly exosomes, are cell-derived nanoscale vesicles that can be engineered via surface ligand/peptide conjugation, membrane protein engineering, and nucleic acid or protein cargo loading to improve targeting, stability, and controlled release. These advances position engineered exosomes as promising platforms for the diagnosis and treatment of orthopedic disorders. Here, we review exosome architecture and biological properties, and systematically summarize extraction, purification, and engineering strategies, alongside their applications to osteoarthritis, osteoporosis, fracture healing, and bone malignancies. Reported therapeutic mechanisms include promotion of osteogenesis and angiogenesis, immunomodulation and anti-inflammatory effects, and regulation of autophagy and apoptosis. Nevertheless, significant barriers remain for clinical translation. To enable routine clinical use, future work should address product heterogeneity, scalable manufacturing, cargo stability, release kinetics, and long-term safety, supported by robust quality control and standardization. Finally, we adopt a technology-centric framework that maps engineering modalities to orthopedic indications and quantifiable performance metrics, outlining the review's methodological route and evidence synthesis approach.

Keywords:  biomedical technology platform; engineered exosomes; orthopedic diseases; precision diagnostics; targeted delivery

DOI:  https://doi.org/10.3389/fmed.2026.1788658
Biol Direct. 2026 Apr 29.

Carbomol hydrogels integrating chlorogenic acid-loaded exosomes promote diabetic wound healing through antibacterial and immunomodulatory activities.

Hehui Wang, Ming Guan, Guangyu Chu, Yue Wang.

  Diabetic wounds represent a significant global clinical challenge, exacerbated by persistent bacterial infection and a dysregulated inflammatory microenvironment. Effective strategies for diabetic wounds are absent. Here, we found that NOD-like receptor thermal protein domain associated protein 3 (NLRP3) is an important regulating molecule associated with inflammatory microenvironment. We engineered Carbomol hydrogels integrating chlorogenic acid-loaded exosomes (Exo-CA@CB) to address both infection and NLRP3-mediated inflammation. The Carbomol hydrogel (CB) matrix provides biocompatibility, adhesion, self-healing properties, and sustained release, while the encapsulated Exo-CA deliver bioactive cargo. In vitro studies demonstrated the potent antibacterial activity of Exo-CA@CB against common wound pathogens. Crucially, Exo-CA@CB effectively promoted macrophage polarization towards the regenerative M2 phenotype. In the infected diabetic wound model, topical application of Exo-CA@CB hydrogels significantly accelerated healing. This study validates a new approach, initiated by single-cell analysis, for developing Exo-CA@CB hydrogels as a promising platform to manage infected diabetic wounds by concurrently tackling infection and NLRP3-driven inflammation.

Keywords:  Antibacterial; Carbomol hydrogel; Chlorogenic acid; Exosomes; Immunomodulation

DOI:  https://doi.org/10.1186/s13062-026-00818-z
J Funct Biomater. 2026 Apr 01. pii: 174. [Epub ahead of print]17(4):

Additive-Manufactured S53P4@PCL Composite Scaffolds Functionalized with Aptamers and Antibacterial Exosomes for Rapid Bacterial Capture and Killing.

Chen Zhang, Runyi Lin, Jinchao You, Yaomei Wang, Haopeng Wang, Yixian Ru, Shunxue Xing, Junxiang Wang, Shan Chen.

  Bone defects remain a significant challenge in bone tissue engineering, driving an urgent need for advanced materials with enhanced therapeutic properties. Additive manufacturing highlights a unique capacity for customization, which enables the precise realization of complex and personalized composite scaffolds. This study innovatively integrates the superior mechanical properties of polycaprolactone (PCL) with the antibacterial characteristics of S53P4 bioactive glass. Utilizing thermal melt extrusion processing and fused deposition modeling (FDM) technology, we fabricated gradient-structured S53P4@PCL composite three-dimensional porous scaffolds with varying doping ratios (5 wt%, 10 wt%, 20 wt%). To further improve the antibacterial efficacy of the scaffold, exosomes (EXO) derived from grouper eggs were functionalized with bacteria-targeting aptamers (APTs), a type of functional DNA capable of binding to bacterial peptidoglycan, and EXO-APT-20%S53P4@PCL was fabricated. The resulting EXO-APT-20%S53P4@PCL scaffold was able to facilitate the targeted capture and subsequent eradication of bacteria. This study pioneers the synergistic integration of aptamer-modified exosomes into 3D composite scaffolds. Our analysis confirmed that the incorporation of APTs enabled targeted bacterial capture, and antibacterial EXO further enhanced the overall bacterial killing capability of the S53P4@PCL scaffolds. The fabrication of porous S53P4@PCL scaffolds through an innovative composite-molding strategy, combined with EXO-APT functionalization, establishes a new paradigm for customized bone repair.

Keywords:  S53P4@PCL; additive manufacturing; bone tissue engineering; exosomes; nucleic acid aptamers

DOI:  https://doi.org/10.3390/jfb17040174
Drug Des Devel Ther. 2026 ;20 590015

Bioengineering Applications of Chinese Herbal Medicine-Derived Exosomes in Cardiovascular Diseases: Mechanisms and Translational Prospects.

Yixin Liu, Yiru Wang, Ming Fang.

  Cardiovascular disease remains the leading cause of death worldwide, with current therapies facing limitations in efficacy and safety. Chinese Herbal Medicine-Derived Exosomes (CHM-Exos) are nano-sized membrane vesicles secreted by herbal cells, capable of cross-species delivery of bioactive substances. While plant-derived extracellular vesicles have been extensively reviewed, analyses specifically focused on CHM-Exos in cardiovascular contexts remain limited. This review systematically examines the bioengineering applications and therapeutic mechanisms of CHM-Exos in cardiovascular diseases, addressing a critical gap in translational literature. Mechanistically, CHM-Exos show potential to alleviate oxidative stress and modulate vascular cell function, though direct cardiovascular evidence remains preliminary. Key translational barriers-including standardization challenges, scalability constraints, and regulatory uncertainties-are critically discussed, alongside strategies to advance these promising nanocarriers toward clinical application.

Keywords:  Chinese herbal medicine-derived exosomes; bioengineering; cardiovascular diseases; engineering modification; targeted delivery

DOI:  https://doi.org/10.2147/DDDT.S590015
J Extracell Vesicles. 2026 May;15(5): e70284

Development of CAR Exosomes Targeting FAP for the Treatment of Intrauterine Adhesion.

Wenyan Fu, Kewen Qian, Hongru Ai, Yitan Zou, Yaping Zhou, Ruixue Mao, Jian Zhao, Changhai Lei, Shi Hu.

  Engineered extracellular vesicles (EVs) have emerged as promising cell-free platforms for immunomodulation and tissue repair. In this study, we generated EVs derived from chimeric antigen receptor (CAR) T cells targeting fibroblast activation protein (FAP) and investigated their biological and therapeutic functions. These FAP-CAR EVs effectively inhibited intrauterine fibrosis, promoted endometrial regeneration, and increased pregnancy rates in a mouse model of intrauterine adhesion. Importantly, the exosome-based therapy did not affect embryonic development or trigger systemic inflammation, indicating high safety compared with T-cell-based treatment. Mechanistically, while FAP-targeted T cells could suppress fibrosis, they also induced severe cytokine-release toxicity, which was completely avoided in the EV-based strategy. Together, these findings demonstrate that FAP is a critical target for fibrotic disease intervention and that CAR-T-derived EVs represent a safe and effective vesicle-based therapeutic modality.

Keywords:  CAR‐T; FAP; exosomes; immunotherapy; intrauterine adhesions

DOI:  https://doi.org/10.1002/jev2.70284
Research (Wash D C). 2026 ;9 1207

NIR-Activated ICG-Loaded M2 Macrophage Exosomes Ameliorate Periodontitis via Targeting Infection Inflammation and Oxidative Stress.

Xincong Li, Xin Fu, Tianyu Zhang, Xiaofan Cheng, Hai Zhuang, Zhilei Mao, Shoushan Bu.

Periodontitis is a chronic bacterial inflammatory disease. M2 macrophage-derived exosomes (M2-exos) possess targeted immunomodulatory abilities, but their role in mitigating oxidative stress (key for periodontitis treatment) remains unclear. In this study, we engineered M2-exos loaded with indocyanine green (ICG) (ICG@M2-exos) for the treatment of periodontitis. The constructed ICG@M2-exos effectively facilitated macrophage reprogramming from the M1 to the M2 phenotype, thereby resolving chronic inflammation and enhancing periodontal tissue repair. Under near-infrared irradiation, ICG conferred potent antibacterial efficacy against Porphyromonas gingivalis (P. gingivalis). Simultaneously, the exosomes released from ICG@M2-exos mitigated oxidative stress and decreased the expression of proinflammatory factors in THP-1 cells through promoting M2 polarization. In a rat model of P. gingivalis-induced periodontitis, the sustained release of ICG@M2-exos markedly expedited periodontal bone regeneration, accompanied by elevated levels of anti-inflammatory cytokines. Collectively, ICG-engineered M2-exos represent a promising strategy for tackling inflammatory periodontal conditions. This study demonstrates the dual advantages of ICG@M2-exos in near-infrared-responsive antibacterial activity and immunomodulation that work synergistically, laying a solid foundation for future clinical applications.

DOI: https://doi.org/10.34133/research.1207
Pharmacol Res. 2026 Apr 28. pii: S1043-6618(26)00132-5. [Epub ahead of print] 108217

Remote Mobilization of Gut Tregs Exosomes serves as Nanoshuttles for Targeted Cardioprotection Against Ischemia/Reperfusion Injury by Ginseng Polysaccharides.

Yuan-Yuan Li, Lin Sun, Yan Wang, Hua-Yi Yang, De-Sheng Xu, Yan-Zhu Zhong, Juan-Hong Zhang, Yang Li, Fang-Cao Pi, Qi-Lu Li, Zi-Rui Li, Wei-Ting Wang, Ming-Tai Chen, Meng-Nan Liu, Qi-di Sun, Ming-Ming Peng, Elaine Lai-Han Leung, Qi-Biao Wu, Ya-Ling Han, Liang Liu, Ying Xie, Yi-Fa Zhou, Hua Zhou.

  Myocardial ischemia-reperfusion injury (MIRI) remains a critical clinical condition with limited preventive and therapeutic strategies, underscoring the need for novel interventions. The gut-heart axis and exosomal crosstalk hold therapeutic promise for cardioprotection, yet the fundamental question of which specific gut cells release the beneficial exosomes is unanswered. This study aimed to elucidate whether ginseng polysaccharides WGPA exert remote cardiac protection by regulating intestinal immune homeostasis, specifically through promoting the release of exosomes from regulatory T cells (Tregs). Using integrated in vivo and in vitro models, we evaluated the protective effects of WGPA against MIRI. The results demonstrated that WGPA pretreatment significantly attenuated myocardial injury and improved cardiac function. Mechanistically, WGPA selectively activated intestinal Tregs and enhanced the release of HSP70-enriched exosomes. These exosomes entered systemic circulation and were delivered to the heart, where surface HSP70 interacted with TLR4 on cardiomyocytes, activating downstream protective signaling pathways and ultimately suppressing cardiomyocyte death and inflammatory responses. Our study reveals for the first time a complete mechanism by which medicinal plant polysaccharides confer cross-organ cardioprotection via the "intestinal Tregs-exosome-heart" axis, providing a novel theoretical basis and a potential intervention strategy for the prevention and treatment of MIRI.

Keywords:  Exosomes; Ginseng polysaccharides WGPA; Gut-heart axis; Myocardial ischemia-reperfusion injury; Regulatory T cells

DOI:  https://doi.org/10.1016/j.phrs.2026.108217
Acta Pharm Sin B. 2026 Apr;16(4): 2570-2586

A spatiotemporal selective bioinspired hybrid system engineered for preventing post-thrombolysis recurrence by inhibiting the ferroptosis pathway and reprogramming macrophages.

Tianjiao Hao, Bin Gao, Yuanyuan Zhou, Chang Liu, Chuanjiang Ran, Binghua Chang, Wei You, Qiyue Wang, Jun Ye, Yan Shen.

  Cardiovascular diseases induced by arterial thrombosis, such as myocardial infarction and ischemic stroke, have gradually emerged as critical threats to human life and health. Sequentially targeted delivery systems are highly desired to be developed to improve the delivery of thrombolytics and anti-inflammatory medications to the site of the thrombus, respectively, to pursue a maximized combinational effect. Herein, we developed a probiotic-platelet hybrid vesicle-targeted drug delivery system (Fer-1@PLevs-C&U) to achieve sequential anti-thrombolytic delivery against thrombus and prevent its recurrence. The hybrid vesicles (PLevs) were prepared by mixing platelet membrane with Lactobacillus plantarum-derived bacterial extracellular vesicles (Levs) and further decorated with DSPE-PEG2000-CREKA, achieving "point-to-point" multi-covalent targeting of thrombus components. After targeted localization to the arterial thrombotic site, Fer-1@PLevs-C&U gradually releases the thrombolytic drug urokinase-type plasminogen activator (UPA) and Ferroptosis inhibitor (Fer-1) to facilitate thrombus dissolution and regulate the inflammatory microenvironment. By enhancing the eNOS expression and reducing the secretion of inflammatory factors TNF-α and IL-6, Fer-1@PLevs-C&U significantly reduced the inflammatory microenvironment and inhibited recurrent thrombus. Therefore, Fer-1@PLevs-C&U constitutes a novel biomimetic drug delivery platform with promising therapeutic potential and practical applicability.

Keywords:  Biomimetic hybrid nanocarriers; Efficient thrombolysis; Ferroptosis; Macrophages regulation; Multiple covalent targeting system; Post-thrombolysis recurrence; Thrombus; Thrombus microenvironment improvement

DOI:  https://doi.org/10.1016/j.apsb.2026.01.014
ACS Appl Mater Interfaces. 2026 Apr 27.

Targeted Biomimetic Stem Cell Membrane-Exosome Composite Delivery System for the Treatment of Bone Defects.

Chong Yin, Jinshu Yu, Hongwei Pang, Min Xu, Binxin Wang, Wei Chen, Ning Xie, Bin Guo.

  Exosomes derived from MC3T3-E1 cells (M-Exos) exhibit considerable potential for promoting bone repair and regulating bone metabolism. However, their limited osteogenic efficiency and poor targeting capacity remain major challenges. In this study, we developed a therapeutic system, HAMA + BM-Exo138. This platform encapsulates exosomes loaded with the recombinant nucleic acid drug MSA-anti-138 within bone marrow mesenchymal stem cell membranes (BMs), generating a BM-Exo138 complex with enhanced bone-targeting ability and therapeutic efficacy. Hyaluronic acid methacrylate (HAMA) hydrogel was employed as a bone-filling material to provide a supportive matrix for the sustained release of BM-Exo138, thereby promoting osteogenic differentiation and facilitating bone defect repair both in vitro and in vivo. RNA sequencing analysis indicated that BM-Exo138 exerts its therapeutic effects by activating the TGF-β signaling pathway. These findings highlight an integration strategy for exosome-based therapy and offer a promising approach to overcoming current limitations in bone defect treatment, with substantial potential for clinical translation.

Keywords:  bionic membrane; bone defects; drug delivery; exosomes; nucleic acid drugs

DOI:  https://doi.org/10.1021/acsami.5c24575
Research (Wash D C). 2026 ;9 1042

Apoptotic Vesicle Membrane-Mediated Targeted Endothelial Mitochondrial Transplantation-Clearance Therapy for Diabetic Wound Healing.

Zheyuan Hu, Shutong Qian, Bo Liao, Yuhuan Wang, Qian Lu, Jiayi Mao, Bolun Lu, Liucheng Zhang, Fei Wang, Danru Wang, Wenguo Cui, Xiaoming Sun.

Impaired mitophagy and the accumulation of damaged mitochondria are key drivers of endothelial cell (EC) dysfunction in diabetic wounds. While mitochondrial transplantation (MT) has demonstrated therapeutic potential in such mitochondrial damage-related diseases, its application is still thwarted by elusive mechanisms and practical hurdles such as poor targeting specificity and low delivery efficiency. Here, we reveal that MT acts by reactivating mitophagy to selectively eliminate dysfunctional mitochondria, thereby restoring mitochondrial homeostasis and rescuing EC functionality. To exploit this discovery, we engineer a biomimetic MT strategy through coating EC-derived apoptotic vesicle membrane (AVM) onto the surface of isolated mitochondria. The resulting mitochondria-AVM complex (Mito-AVM) leverages homologous targeting and phosphatidylserine-mediated "eat-me" signaling, achieving a remarkable 150% increase in delivery efficiency to ECs in diabetic wounds. Furthermore, we construct a 3-aminophenylboric acid-modified hyaluronic acid/polyvinyl alcohol hydrogel for the diabetic wound microenvironment, enabling reactive oxygen species/glucose-triggered sustained release of encapsulated Mito-AVM at the wound site. In summary, our work elucidates a fundamental mechanism of MT and provides an efficient and targeted strategy for MT therapy, offering fresh perspectives for diabetic wound treatment.

DOI: https://doi.org/10.34133/research.1042
J Extracell Biol. 2026 May;5 e70131

Extracellular Vesicles in Osteoarthritis: From Pathogenic Mediators to Engineered Therapeutics in a Precision Medicine Roadmap.

Duc-Hiep Bach, Van Giang Bui, Thanh Liem Nguyen.

Osteoarthritis (OA) remains without disease-modifying sssstherapies, in part due to biological heterogeneity and a hostile joint microenvironment that undermines one-size-fits-all interventions. Extracellular vesicles (EVs) play a dual role in OA pathophysiology: endogenous EVs disseminate pro-inflammatory and catabolic signals that propagate cartilage degeneration, whereas therapeutic EVs most commonly derived from regenerative cell sources can deliver anti-inflammatory and anabolic cues. We frame this contrast as the EV paradox and argue that it represents a central translational challenge explaining why robust preclinical efficacy has not yet translated into consistent clinical benefit. We synthesize current evidence on EV biology in joint tissues, outcomes across preclinical models, and early human studies that demonstrate safety but limited efficacy. This analysis highlights key barriers to translation, including impaired EV function within inflamed and mechanically active joints, rapid clearance and limited tissue targeting, mismatch between animal models and human disease, and insufficient standardization of EV potency. Building on these insights, we propose a precision-medicine roadmap that emphasizes patient stratification, rational EV design, improved delivery strategies, and manufacturing frameworks linked to mechanism-anchored endpoints. Together, this framework reframes the EV paradox from a translational obstacle into a design principle for developing disease-modifying EV-based therapies for OA.

DOI: https://doi.org/10.1002/jex2.70131