A natural extracellular matrix hydrogel through selective nutrient restriction for hyperinflammatory starvation therapy

An adequate nutrient supply is essential for maintaining the function of highly active immune cells; however, in an environment of excessive inflammation, this nutrient supply aggravates inflammation. We propose a “hyperinflammatory starvation therapy” for various diseases caused by excessive metabolism by highly selective restriction of the supply of local nutrients. Here we developed a natural, physiologically triggered, injectable, nano-platelet vesicle-based extracellular matrix hydrogel (NPV-ECM). As a proof of concept, in representative excessive inflammatory disease diabetic wounds, we demonstrated that the NPV-ECM can selectively regulate nutrient transportation based on intermolecular interactions, remodel the local immune microenvironment, limit the state of excess metabolism, promote angiogenesis, and achieve wound healing. Moving into the clinic, we conducted a clinical trial in patients with diabetic foot ulcers to verify the safety and therapeutic effect of the NPV-ECM. This study provides an understanding of the preparation and application of natural ECM biomaterials for hyperinflammatory starvation therapy.