TY - JOUR
T1 - Intravascularly infused extracellular matrix as a biomaterial for targeting and treating inflamed tissues
AU - Spang, Martin T.
AU - Middleton, Ryan
AU - Diaz, Miranda
AU - Hunter, Jervaughn
AU - Mesfin, Joshua
AU - Banka, Alison
AU - Sullivan, Holly
AU - Wang, Raymond
AU - Lazerson, Tori S.
AU - Bhatia, Saumya
AU - Corbitt, James
AU - D’Elia, Gavin
AU - Sandoval-Gomez, Gerardo
AU - Kandell, Rebecca
AU - Vratsanos, Maria A.
AU - Gnanasekaran, Karthikeyan
AU - Kato, Takayuki
AU - Igata, Sachiyo
AU - Luo, Colin
AU - Osborn, Kent G.
AU - Gianneschi, Nathan C.
AU - Eniola-Adefeso, Omolola
AU - Cabrales, Pedro
AU - Kwon, Ester J.
AU - Contijoch, Francisco
AU - Reeves, Ryan R.
AU - DeMaria, Anthony N.
AU - Christman, Karen L.
N1 - Funding Information:
We thank J. Placone for confocal imaging assistance, M. Davis for providing the rat cardiac endothelial cells, P. Duran for helpful comments during the manuscript-editing process, and the veterinary staff at the Institutional Animal Care and Use Program of the University of California, San Diego, for assistance with large-animal procedures and safety. K.L.C. and O.E.-A. acknowledge funding support for the research described in this study from the NIH NHLBI (grant numbers R01HL113468, 1R01HL165232 and R43HL150917 to K.L.C. and R01HL145709 to O.E.-A). M.T.S., M.D., J.H. and R.W. acknowledge support from the NIH NHLBI (grant number T32HL105373). M.D., J.H., H.S. and R.W. acknowledge support from the NIH NHLBI (grant numbers F31HL152686, F31HL158212, F31HL152610 and F31HL137347). M.T.S. acknowledges support from an A.H.A. predoctoral fellowship. M.A.V. acknowledges support from the N.S.F. (grant number DGE-1842165) and the Dr. John N. Nicholson Fellowship, which was awarded by Northwestern University. This work made use of the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (Grant ECCS-2025752), and the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern’s MRSEC program (NSF DMR-1720139).
Funding Information:
We thank J. Placone for confocal imaging assistance, M. Davis for providing the rat cardiac endothelial cells, P. Duran for helpful comments during the manuscript-editing process, and the veterinary staff at the Institutional Animal Care and Use Program of the University of California, San Diego, for assistance with large-animal procedures and safety. K.L.C. and O.E.-A. acknowledge funding support for the research described in this study from the NIH NHLBI (grant numbers R01HL113468, 1R01HL165232 and R43HL150917 to K.L.C. and R01HL145709 to O.E.-A). M.T.S., M.D., J.H. and R.W. acknowledge support from the NIH NHLBI (grant number T32HL105373). M.D., J.H., H.S. and R.W. acknowledge support from the NIH NHLBI (grant numbers F31HL152686, F31HL158212, F31HL152610 and F31HL137347). M.T.S. acknowledges support from an A.H.A. predoctoral fellowship. M.A.V. acknowledges support from the N.S.F. (grant number DGE-1842165) and the Dr. John N. Nicholson Fellowship, which was awarded by Northwestern University. This work made use of the San Diego Nanotechnology Infrastructure (SDNI) of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation (Grant ECCS-2025752), and the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN, and Northwestern’s MRSEC program (NSF DMR-1720139).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/2
Y1 - 2023/2
N2 - 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’.
AB - 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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U2 - 10.1038/s41551-022-00964-5
DO - 10.1038/s41551-022-00964-5
M3 - Article
C2 - 36581694
AN - SCOPUS:85145219959
SN - 2157-846X
VL - 7
SP - 94
EP - 109
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 2
ER -