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Review
. 2024 Jul 18:12:tkae023.
doi: 10.1093/burnst/tkae023. eCollection 2024.

Engineered exosomes as a prospective therapy for diabetic foot ulcers

Lifei Guo  1   2   3 , Dan Xiao  1   2 , Helin Xing  4 , Guodong Yang  2 , Xuekang Yang  1
Affiliations
Review

Engineered exosomes as a prospective therapy for diabetic foot ulcers

Lifei Guo et al. Burns Trauma. .

Abstract

Diabetic foot ulcer (DFU), characterized by high recurrence rate, amputations and mortality, poses a significant challenge in diabetes management. The complex pathology involves dysregulated glucose homeostasis leading to systemic and local microenvironmental complications, including peripheral neuropathy, micro- and macro-angiopathy, recurrent infection, persistent inflammation and dysregulated re-epithelialization. Novel approaches to accelerate DFU healing are actively pursued, with a focus on utilizing exosomes. Exosomes are natural nanovesicles mediating cellular communication and containing diverse functional molecular cargos, including DNA, mRNA, microRNA (miRNA), lncRNA, proteins, lipids and metabolites. While some exosomes show promise in modulating cellular function and promoting ulcer healing, their efficacy is limited by low yield, impurities, low loading content and inadequate targeting. Engineering exosomes to enhance their curative activity represents a potentially more efficient approach for DFUs. This could facilitate focused repair and regeneration of nerves, blood vessels and soft tissue after ulcer development. This review provides an overview of DFU pathogenesis, strategies for exosome engineering and the targeted therapeutic application of engineered exosomes in addressing critical pathological changes associated with DFUs.

Keywords: Diabetic angiopathy; Diabetic foot; Diabetic peripheral neuropathy; Engineered exosomes; Foot ulcer; Inflammation; Re-epithelialization; Wound healing; Wound infection.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
Pathology of diabetic foot ulcers. The primary predisposing factors for diabetic foot ulcers include diabetic angiopathy (leading to ischemic ulceration) and peripheral neuropathy (resulting in neuropathic ulceration). Moreover, pathological conditions within the wound microenvironment, such as microangiopathy, sustained inflammation, repeated infection and dysregulated re-epithelialization, contribute to the failure of ulcer healing. Figure created using BioRender (https://biorender.com/)
Figure 2
Figure 2
Schematic workflow of the two routes of engineered exosome preparation. Engineered exosomes produced through parental cell-based engineering undergo a sequential process involving pre-isolation modification of parental cells, followed by exosome isolation and characterization. If not modified before separation, exosomes can undergo post-isolation modification and subsequent characterization. In both routes, exosome engineering involves loading cargo and modifying targeting using various techniques. Figure created using BioRender (https://biorender.com/). ADSCs adipose-derived stem cells, AF4 asymmetric flow field-flow fractionation, BMSCs bone marrow mesenchymal/stem stromal cells, DLS dynamic light scattering, EPCs endothelial progenitor cells, FCM flow cytometry, NTA nanoparticle tracking analysis, RPS resistive pulse sensing, SEM scanning electron microscope, SMSCs synovium mesenchymal stem cells, TEM transmission electron microscope, WB western blot
Figure 3
Figure 3
The role of engineered exosomes in the treatment of diabetic foot ulcers. The application of engineered exosomes targets the pathogenesis and pathological microenvironment of diabetic foot ulcers, including vascular repair and angiogenesis, nerve regeneration, anti-infection measures, management of sustained inflammation, and re-epithelialization. Figure created using BioRender (https://biorender.com/). LDL low-density lipoprotein, LDLR low-density lipoprotein receptor, Lamp2b lysosome associated membrane protein-2b, EpSC epidermal stem cells, AGE advanced glycation end products, RAGE receptor for AGE
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