Journal article
Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling
Circulation. Cardiovascular interventions, v 9(10)
Oct 2016
PMID: 27729419
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Injectable, acellular biomaterials hold promise to limit left ventricular remodeling and heart failure precipitated by infarction through bulking or stiffening the infarct region. A material with tunable properties (eg, mechanics, degradation) that can be delivered percutaneously has not yet been demonstrated. Catheter-deliverable soft hydrogels with in vivo stiffening to enhance therapeutic efficacy achieve these requirements.
We developed a hyaluronic acid hydrogel that uses a tandem crosslinking approach, where the first crosslinking (guest-host) enabled injection and localized retention of a soft (<1 kPa) hydrogel. A second crosslinking reaction (dual-crosslinking) stiffened the hydrogel (41.4±4.3 kPa) after injection. Posterolateral infarcts were investigated in an ovine model (n≥6 per group), with injection of saline (myocardial infarction control), guest-host hydrogels, or dual-crosslinking hydrogels. Computational (day 1), histological (1 day, 8 weeks), morphological, and functional (0, 2, and 8 weeks) outcomes were evaluated. Finite-element modeling projected myofiber stress reduction (>50%; P<0.001) with dual-crosslinking but not guest-host injection. Remodeling, assessed by infarct thickness and left ventricular volume, was mitigated by hydrogel treatment. Ejection fraction was improved, relative to myocardial infarction at 8 weeks, with dual-crosslinking (37% improvement; P=0.014) and guest-host (15% improvement; P=0.058) treatments. Percutaneous delivery via endocardial injection was investigated with fluoroscopic and echocardiographic guidance, with delivery visualized by magnetic resonance imaging.
A percutaneous delivered hydrogel system was developed, and hydrogels with increased stiffness were found to be most effective in ameliorating left ventricular remodeling and preserving function. Ultimately, engineered systems such as these have the potential to provide effective clinical options to limit remodeling in patients after infarction.
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Details
- Title
- Injectable Shear-Thinning Hydrogels for Minimally Invasive Delivery to Infarcted Myocardium to Limit Left Ventricular Remodeling
- Creators
- Christopher B Rodell - University of PennsylvaniaMadonna E Lee - University of KentuckyHua Wang - University of KentuckySatoshi Takebayashi - University of KentuckyTetsushi Takayama - University of KentuckyTomonori Kawamura - University of KentuckyJeffrey S Arkles - University of KentuckyNeville N Dusaj - University of KentuckyShauna M Dorsey - University of KentuckyWalter R T Witschey - University of KentuckyJames J Pilla - University of KentuckyJoseph H Gorman, 3rdJonathan F Wenk - University of KentuckyJason A Burdick - University of KentuckyRobert C Gorman - University of Kentucky
- Publication Details
- Circulation. Cardiovascular interventions, v 9(10)
- Grant note
- R01 HL063954 / NHLBI NIH HHS R01 HL111090 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000386910500008
- Scopus ID
- 2-s2.0-84992111157
- Other Identifier
- 991019176642604721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems