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Merck

Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.

Nature biomedical engineering (2022-12-30)
Martin T Spang, Ryan Middleton, Miranda Diaz, Jervaughn Hunter, Joshua Mesfin, Alison Banka, Holly Sullivan, Raymond Wang, Tori S Lazerson, Saumya Bhatia, James Corbitt, Gavin D'Elia, Gerardo Sandoval-Gomez, Rebecca Kandell, Maria A Vratsanos, Karthikeyan Gnanasekaran, Takayuki Kato, Sachiyo Igata, Colin Luo, Kent G Osborn, Nathan C Gianneschi, Omolola Eniola-Adefeso, Pedro Cabrales, Ester J Kwon, Francisco Contijoch, Ryan R Reeves, Anthony N DeMaria, Karen L Christman
ABSTRAKT

Decellularized extracellular matrix in the form of patches and locally injected hydrogels has long been used as therapies in animal models of disease. Here we report the safety and feasibility of an intravascularly infused extracellular matrix as a biomaterial for the repair of tissue in animal models of acute myocardial infarction, traumatic brain injury and pulmonary arterial hypertension. The biomaterial consists of decellularized, enzymatically digested and fractionated ventricular myocardium, localizes to injured tissues by binding to leaky microvasculature, and is largely degraded in about 3 d. In rats and pigs with induced acute myocardial infarction followed by intracoronary infusion of the biomaterial, we observed substantially reduced left ventricular volumes and improved wall-motion scores, as well as differential expression of genes associated with tissue repair and inflammation. Delivering pro-healing extracellular matrix by intravascular infusion post injury may provide translational advantages for the healing of inflamed tissues 'from the inside out'.

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