Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues.
Martin T SpangRyan MiddletonMiranda DiazJervaughn HunterJoshua M MesfinAlison L BankaHolly SullivanRaymond WangTori S LazersonSaumya BhatiaJames CorbittGavin D'EliaGerardo Sandoval-GomezRebecca KandellMaria A VratsanosKarthikeyan GnanasekaranTakayuki KatoSachiyo IgataColin LuoKent G OsbornNathan C GianneschiOmolola Eniola-AdefesoPedro CabralesEster J KwonFrancisco J ContijochRyan R ReevesAnthony N DeMariaKaren L ChristmanPublished in: Nature biomedical engineering (2022)
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'.
Keyphrases
- extracellular matrix
- acute myocardial infarction
- left ventricular
- pulmonary arterial hypertension
- traumatic brain injury
- gene expression
- percutaneous coronary intervention
- heart failure
- pulmonary artery
- tissue engineering
- low dose
- pulmonary hypertension
- oxidative stress
- hypertrophic cardiomyopathy
- coronary artery
- left atrial
- aortic stenosis
- acute coronary syndrome
- diabetic rats
- st elevation myocardial infarction
- high glucose
- coronary artery disease
- atrial fibrillation
- heavy metals
- drug delivery
- cancer therapy
- endothelial cells
- sewage sludge
- drug release