What question did this study set out to answer?

This study aims to explore the effects of engineered exosomes in 3D printed bioengineered skin for treating diabetic chronic wounds in mice.

June 8, 2026

1156-OR: Engineered Exosome in 3D Printed Skin Substitutes Contributes to Chronic Diabetic Wounds in Mice with Hind-Limb Ischemia by Regulating Rigidity Sensing

Key Points

This study aims to explore the effects of engineered exosomes in 3D printed bioengineered skin for treating diabetic chronic wounds in mice.
Used a multifunctional hybrid 3D bioprinting platform for creating structures with micro-vessels.
Incorporated exosomes from MSCs stimulated by GLP-1(32-36) into hydrogel for bio-3D printing.
Conducted single-cell proteomic analysis to investigate mechanisms of the engineered skin.
GLP-1(32-36) treated exosome-loaded artificial skin improved blood flow and accelerated wound healing.
Promoted collagen production and enhanced rigidity-sensing contractions in endothelial cells.
In vitro, engineered exosomes improved vessel length, connectivity, and diameter in vascular structures.

Abstract

Introduction and Objective: Diabetic foot ulcers complicated by lower limb ischemia are common complications in the person with diabetes, leading to non-traumatic amputations. Currently, there are no specific drugs, and treatment is limited to surgical intervention. This study explores the therapeutic effects and mechanisms of multi-cell fusion-based 3D-printed bioengineered skin, incorporating engineered exosomes, for treating diabetic chronic wounds with lower limb ischemia. Methods: A multifunctional hybrid 3D bioprinting platform combining inkjet and extrusion was used to create complex structures, including free-form 3D shapes with embedded micro-vessels. Exosomes from MSCs stimulated by the GLP-1 end product-GLP-1(32-36) were incorporated into hydrogel for bio-3D printing. Therapeutic effects have been demonstrated in T2DM mice and porcine wound models. Single-cell proteomic was employed to investigate the mechanisms of exosome-loaded “artificial skin”. Results: In vivo, GLP-1(32-36) treated exosome-loaded “artificial skin” (32-36AS) significantly improved blood flow, accelerated wound healing, and promoted collagen production. Single-cell proteomic analysis showed that 32-36AS especially promoted rigidity-sensing contractions in ECs and attenuate mouse dermal fibroblast (MDFs) and keratinocytes (KCs) mediated scar formation. Depletion of cytoskeletal proteins, including tropomyosins (Tpm2.1 and 3.1) would block the 32-36AS mediated angiogenesis and wound healing. In vitro, GLP-1(32-36) engineered exosomes enhanced tube formation and migration of ECs and fibroblasts. They also improved vascular structures, increasing vessel length, connectivity, and diameter distribution, forming a dense fibrovascular network. Conclusion: This study develops multicellular vascularized 32-36AS with bio-3D printing, providing a foundation for clinical application in treating diabetic foot ulcers with lower limb ischemia. Disclosure Y. Zhang: None. M. Gao: None. S. Zhang: None. Y. Wan: None. C. Zheng: None.

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