Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Decellularized extracellular matrix (ECM) hydrogels offer native complexity and injectability.
• Current ECM hydrogels lack tunable properties without synthetic additives or altered ligand landscapes.

Purpose of the Study:

• To develop genetically tunable ECM-derived hydrogels.
• To investigate the impact of thrombospondin-2 (TSP-2) knockout on hydrogel properties and in vivo performance.
• To explore the potential of genetically engineered cell-derived matrix hydrogels.

Main Methods:

• Fabrication of hydrogels from wild-type (WT) and TSP-2 knockout (KO) decellularized skin.
• Characterization of mechanical properties using rheology and collagen content via quantitative proteomics.
• In vivo assessment of cell invasion and diabetic wound healing.
• Preparation and evaluation of hydrogels from genetically engineered cell-derived matrix.

Main Results:

• Genetically modified ECM hydrogels exhibited distinct mechanical properties and collagen concentrations.
• Hydrogel mixtures allowed for intermediate property tuning.
• In vivo, TSP-2 KO hydrogel content correlated with tunable cell invasion.
• TSP-2 KO hydrogels significantly enhanced diabetic wound healing at 10 and 21 days.
• Cell-derived matrix hydrogels mimicked tissue-derived matrix trends.

Conclusions:

• Genetic engineering provides a method for tuning ECM-based hydrogel properties.
• TSP-2 KO hydrogels demonstrate potential for enhanced tissue regeneration, particularly in wound healing.
• Genetically engineered cell-derived matrices offer a scalable platform for biomaterial development and clinical translation.