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

Spang, Martin T.; Middleton, Ryan; Diaz, Miranda D.; Hunter, Jervaughn; Mesfin, Joshua M.; Banka, Alison; Sullivan, Holly L.; Wang, Raymond; Lazerson, Tori S; Bhatia, Saumya; Corbitt, James; D'Elia, Gavin; Sandoval-Gomez, Gerardo; Kandell, Rebecca M; Vratsanos, Maria; Gnanasekaran, Karthikeyan; Kitasaka, Takayuki; Igata, Sachiyo; Luo, Claire; Osborn, Kent G.; Gianneschi, Nathan C.; Eniola‐Adefeso, Omolola; Cabrales, Pedro; Kwon, Ester J.; Contijoch, Francisco; Reeves, Ryan; DeMaria, Anthony N.; Christman, Karen L.

doi:10.1038/s41551-022-00964-5

Cited by 29 publications

(33 citation statements)

References 62 publications

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“…For fluorescently labeled iECM or trilysine, the material was conjugated at room temperature for a minimum of 1 h before injection with 10 mg mL −1 of either VivoTag 750 (PerkinElmer, dilution 1:1000) or AlexaFluor 568 (Invitrogen, dilution 1:100) as previously described. [12] Infusible Extracellular Matrix Characterization and Quality Control: The iECM was characterized as previously described. [12] In short, the iECM peptide size and distribution were visualized through SDS-PAGE using a 4-12% Bis-Tris gel NuPage Kit (Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…[12] Infusible Extracellular Matrix Characterization and Quality Control: The iECM was characterized as previously described. [12] In short, the iECM peptide size and distribution were visualized through SDS-PAGE using a 4-12% Bis-Tris gel NuPage Kit (Invitrogen). The controls were a rat tail collagen type I, the full ECM hydrogel counterpart from the same biological batch of hearts, and an Abcam Prestained Protein Ladder Broad molecular weight ranging from 10-245 kDa (ab116028).…”

Section: Methodsmentioning

confidence: 99%

“…In previous applications of the iECM in acute MI, the material reduced the vascular permeability of albumin in the infarct region, which provided motivation for the application of iECM for mitigating increased vascular permeability and BBB dysfunction in TBI. [12] To determine the effects of the iECM on vascular permeability in vivo, we measured the extravasation of two molecular weight tracers after i.v. delivery of iECM or saline in CCI-injured mice.…”

Section: Iecm Reduces Vascular Permeability In Vivo and In Vitromentioning

confidence: 99%

“…[37][38][39][40] This data is reflective of the neovascularization modulation seen in acute MI in which the iECM upregulated genes such as Vegfa, Bmp7, Nrg1, and Fgf2 via NanoString analysis. [12] These mechanisms may provide insight into the interaction between iECM and vascular repair.…”

Section: Iecm Modulates Pathways Of Neuroinflammationmentioning

confidence: 99%

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Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury

Diaz

Kandell

et al. 2023

Adv Healthcare Materials

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Traumatic brain injury (TBI) affects millions of people each year and, in many cases, results in long‐term disabilities. Once a TBI has occurred, there is a significant breakdown of the blood−brain barrier resulting in increased vascular permeability and progression of the injury. In this study, the use of an infusible extracellular matrix‐derived biomaterial (iECM) for its ability to reduce vascular permeability and modulate gene expression in the injured brain is investigated. First, the pharmacokinetics of iECM administration in a mouse model of TBI is characterized, and the robust accumulation of iECM at the site of injury is demonstrated. Next, it is shown that iECM administration after injury can reduce the extravasation of molecules into the brain, and in vitro, iECM increases trans‐endothelial electrical resistance across a monolayer of TNFα‐stimulated endothelial cells. In gene expression analysis of brain tissue, iECM induces changes that are indicative of downregulation of the proinflammatory response 1‐day post‐injury/treatment and neuroprotection at 5 days post‐injury/treatment. Therefore, iECM shows potential as a treatment for TBI.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Iecm Reduces Vascular Permeability In Vivo and In Vitromentioning

confidence: 99%

Section: Iecm Modulates Pathways Of Neuroinflammationmentioning

confidence: 99%

See 2 more Smart Citations

Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury

Diaz

Kandell

et al. 2023

Adv Healthcare Materials

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“…This PDF file includes: Materials and Methods Fig. S1 to S21 Table S1 to S11 References (57)(58)(59)(60)(61)(62)(63) Other Supplementary Material for this manuscript includes the following: Data file S1 MDAR Reproducibility Checklist…”

Section: Supplementary Materialsmentioning

confidence: 99%

Proregenerative extracellular matrix hydrogel mitigates pathological alterations of pelvic skeletal muscles after birth injury

et al. 2023

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Pelvic floor disorders, including pelvic organ prolapse and urinary and fecal incontinence, affect millions of women globally and represent a major public health concern. Pelvic floor muscle (PFM) dysfunction has been identified as one of the leading risk factors for the development of these morbid conditions. Childbirth, specifically vaginal delivery, has been recognized as the most important potentially modifiable risk factor for PFM injury; however, the precise mechanisms of PFM dysfunction after parturition remain elusive. In this study, we demonstrated that PFMs exhibit atrophy and fibrosis in parous women with symptomatic pelvic organ prolapse. These pathological alterations were recapitulated in a preclinical rat model of simulated birth injury (SBI). The transcriptional signature of PFMs after injury demonstrated an impairment in muscle anabolism, persistent expression of genes that promote extracellular matrix (ECM) deposition, and a sustained inflammatory response. We also evaluated the administration of acellular injectable skeletal muscle ECM hydrogel for the prevention of these pathological alterations. Treatment of PFMs with the ECM hydrogel either at the time of birth injury or 4 weeks after injury mitigated PFM atrophy and fibrosis. By evaluating gene expression, we demonstrated that these changes are mainly driven by the hydrogel-induced enhancement of endogenous myogenesis, ECM remodeling, and modulation of the immune response. This work furthers our understanding of PFM birth injury and demonstrates proof of concept for future investigations of proregenerative biomaterial approaches for the treatment of injured pelvic soft tissues.

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Intravascularly Deliverable Biomaterial Platforms for Tissue Repair and Regeneration Post‐Myocardial Infarction

et al. 2023

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Each year, nearly 19 million people die of cardiovascular disease with coronary heart disease and myocardial infarction (MI) as the leading cause for the progression of heart failure. Due to the high risk associated with surgical procedures, a variety of minimally invasive therapeutics aimed at tissue repair and regeneration are being developed. While biomaterials delivered via intramyocardial injection have shown promise, there are challenges associated with delivery in acute MI. In contrast, intravascularly injectable biomaterials are a desirable category of therapeutics due to their ability to be delivered immediately post‐MI via less invasive methods. In addition to passive diffusion into the infarct, these biomaterials can be designed to target the molecular and cellular characteristics seen in MI pathophysiology, such as cells and proteins present in the ischemic myocardium, to reduce off‐target localization. These injectable materials can also be stimuli responsive through enzymes or chemical imbalances. This review outlines the natural and synthetic biomaterial designs that allow for retention and accumulation within the infarct via intravascular delivery, including intracoronary infusion and intravenous injection.This article is protected by copyright. All rights reserved

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

Cited by 29 publications

References 62 publications

Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury

Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury

Proregenerative extracellular matrix hydrogel mitigates pathological alterations of pelvic skeletal muscles after birth injury

Intravascularly Deliverable Biomaterial Platforms for Tissue Repair and Regeneration Post‐Myocardial Infarction

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