Sprayable bioadhesive microcarriers loaded with Tβ4-Engineered ADSC exosomes for diabetic wound healing

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Immunology

Background:

• Stem cell-derived therapeutics offer promise for diabetic wound healing but face challenges in stability, retention, and usability.
• Existing treatments struggle to effectively recalibrate the immune microenvironment of chronic diabetic wounds.

Purpose of the Study:

• To develop a novel, sprayable microcarrier platform for delivering thymosin β4 (Tβ4)-overexpressing stem cell-derived exosomes to diabetic wounds.
• To enhance the stability, retention, and therapeutic efficacy of exosome delivery for chronic wound repair.

Main Methods:

• Genetically engineered adipose-derived stem cells (ADSCs) to overexpress Tβ4.
• Encapsulated Tβ4-overexpressing exosomes into hydrogel microcarriers using microfluidic fabrication.
• Functionalized microcarriers with a mesoporous polydopamine (mPDA) coating for enhanced adhesion and retention.
• Evaluated the system's performance in diabetic wound models.

Main Results:

• The EXOs^Tβ4/mPDA@MS system demonstrated stabilized exosome payload and enabled spray-based administration.
• Microcarriers provided sustained, localized exosome release, enhancing macrophage efferocytosis and suppressing inflammation.
• Significant acceleration of wound repair was observed in diabetic models.

Conclusions:

• The engineered microcarrier platform offers a stable, minimally invasive, and clinically adaptable strategy for diabetic wound repair.
• This sprayable and adhesive system advances stem cell-derived exosome therapies for chronic wound management.