Engineering EVs Via ZnBGs-Integrated 3D Dynamic Culture for Type II Diabetic Pressure Ulcer Therapy

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Biology

Background:

• Diabetic pressure ulcers (PUs) present significant clinical challenges due to impaired vascular and neural networks, exacerbated by immobility.
• Current extracellular vesicle (EV) production methods for therapeutic use face limitations in scalability, drug stability, and structural integrity.
• Metal-doped bioactive glass (mBGs) extracts offer a non-destructive method to induce cellular changes and functionalize EVs via ion release and mineralization.

Purpose of the Study:

• To develop a scalable and function-directed platform for producing enhanced extracellular vesicles (EVs) for the treatment of type II diabetic pressure ulcers.
• To investigate the efficacy of zinc-doped bioactive glass (ZnBG) extract combined with 3D dynamic cell culture for improved EV production and function.
• To evaluate the therapeutic potential of these engineered EVs in promoting vascular and neural repair in a diabetic pressure ulcer model.

Main Methods:

• Coupling zinc-doped bioactive glass (ZnBG) extract with 3D dynamic cell culture technology to enhance extracellular vesicle (EV) production.
• Characterizing the protein yield and functional properties (angiogenic, neurogenic) of the produced EVs.
• Utilizing a Sprague-Dawley (SD) rat model of type II diabetic pressure ulcers to assess therapeutic efficacy.
• Investigating the underlying molecular mechanisms, including the PI3K-AKT-HIF-1α axis.

Main Results:

• The 3D-ZnBG-EVs demonstrated significantly increased protein yield compared to conventional methods.
• Enhanced angiogenic and neurogenic functions were observed in the engineered EVs, mediated by the PI3K-AKT-HIF-1α signaling pathway.
• Treatment with ZnBG-EVs in a diabetic rat model significantly improved vascular and neural repair, extracellular matrix deposition, collagen maturation, and accelerated wound closure.

Conclusions:

• The integrated strategy of using ZnBG extract with 3D dynamic cell culture provides a scalable and effective platform for producing function-directed EVs.
• This approach overcomes limitations of conventional EV production, offering a promising therapeutic strategy for diabetic pressure ulcers.
• The enhanced EVs promote significant improvements in wound healing by facilitating vascular and neural regeneration and tissue remodeling.