Healing Tissues From the Inside Out: Infusible Biomaterial for Targeting and Treating Inflammatory Tissues via Intravascular Administration
Autor: | Martin T. Spang, Ryan Middleton, Miranda Diaz, Raymond Wang, Jervaughn Hunter, Joshua Mesfin, Tori S. Lazerson, Saumya Bhatia, James Corbitt, Gavin D’Elia, Gerardo Sandoval-Gomez, Rebecca Kandell, Takayuki Kato, Sachiyo Igata, Colin Luo, Kent G. Osborn, Pedro Cabrales, Ester Kwon, Francisco Contijoch, Ryan R. Reeves, Anthony N. DeMaria, Karen L. Christman |
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Rok vydání: | 2020 |
Předmět: |
0303 health sciences
Pathology medicine.medical_specialty Decellularization Traumatic brain injury business.industry Biomaterial Inflammation 030204 cardiovascular system & hematology medicine.disease 3. Good health Extracellular matrix 03 medical and health sciences 0302 clinical medicine Tissue engineering Self-healing hydrogels medicine Myocardial infarction medicine.symptom business 030304 developmental biology |
Popis: | Biomaterials, such as extracellular matrix (ECM) hydrogels, have been widely used in preclinical studies as injectable tissue engineering therapies; however, injectable therapies are limited as they can cause localized trauma or organ perforation. We have developed a new ECM therapy, the low molecular weight fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM can be infused after injury, specifically localize to injured tissues by coating the leaky microvasculature, and promote cell survival and tissue repair. In this study, we show the feasibility and targeting of intravascular ECM infusions using models of acute myocardial infarction (MI), traumatic brain injury, and pulmonary arterial hypertension. Furthermore, safety and efficacy were demonstrated in small and large animal models of acute MI following intracoronary infusion, which included using a clinically-relevant catheter in the large animal model. Functional improvements, specifically reduced left ventricular volumes and improved wall motion scores were observed after ECM infusions post-MI. Genes related to tissue repair and inflammation were differential expressed in response to ECM infusions. This study shows proof-of-concept for a new paradigm of delivering pro-healing ECM biomaterials via intravascular infusion to heal tissue from the inside out. |
Databáze: | OpenAIRE |
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