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Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences.

ABSTRACT: Intramyocardial biomaterial injection therapy for myocardial infarction has made significant progress since concept initiation more than 10 years ago. The interim successes and progress in the first 5 years have been extensively reviewed. During the last 5 years, two phase II clinical trials have reported their long term follow up results and many additional biomaterial candidates have reached preclinical and clinical testing. Also in recent years deeper investigations into the mechanisms behind the beneficial effects associated with biomaterial injection therapy have been pursued, and a variety of process and material parameters have been evaluated for their impact on therapeutic outcomes. This review explores the advances made in this biomaterial-centered approach to ischemic cardiomyopathy and discusses potential future research directions as this therapy seeks to positively impact patients suffering from one of the world's most common sources of mortality.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC5827941 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences.

Zhu Yang Y Matsumura Yasumoto Y Wagner William R WR

Biomaterials 20170301

Intramyocardial biomaterial injection therapy for myocardial infarction has made significant progress since concept initiation more than 10 years ago. The interim successes and progress in the first 5 years have been extensively reviewed. During the last 5 years, two phase II clinical trials have reported their long term follow up results and many additional biomaterial candidates have reached preclinical and clinical testing. Also in recent years deeper investigations into the mechanisms behind ...[more]

PMID: 28324864

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Project description:Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge about the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To identify the mechanism of action, we examined previously unobtainable measurements of cardiac function from in vivo, ex vivo, and in silico states of clinically relevant heart failure (HF) in large animals. High-resolution ex vivo magnetic resonance imaging and histological data were used along with state-of-the-art subject-specific computational model simulations. Ex vivo data were incorporated in detailed geometric computational models for swine hearts in health (n = 5), ischemic HF (n = 5), and ischemic HF treated with alginate hydrogel injection therapy (n = 5). Hydrogel injection therapy mitigated elongation of sarcomere lengths (1.68 ± 0.10μm [treated] vs. 1.78 ± 0.15μm [untreated], p<0.001). Systolic contractility in treated animals improved substantially (ejection fraction = 43.9 ± 2.8% [treated] vs. 34.7 ± 2.7% [untreated], p<0.01). The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as an LV mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated HF controls without causing negative secondary outcomes to cardiac function. STATEMENT OF SIGNIFICANCE: Heart failure is considered a growing epidemic and hence an important health problem in the US and worldwide. Its high prevalence (5.8 million and 23 million, respectively) is expected to increase by 25% in the US alone by 2030. Heart failure is associated with high morbidity and mortality, has a 5-year mortality rate of 50%, and contributes considerably to the overall cost of health care ($53.1 billion in the US by 2030). Despite positive initial outcomes emerging from preclinical and early clinical investigation of alginate hydrogel injection therapy as a treatment for heart failure, the lack of knowledge concerning the mechanism of action remains a major shortcoming that limits the efficacy of treatment design. To understand the mechanism of action, we combined high-resolution ex vivo magnetic resonance imaging and histological data in swine with state-of-the-art subject-specific computational model simulations. The in silico models realistically simulated in vivo function with >99% accuracy and predicted small myofiber strain in the vicinity of the solidified hydrogel that was sustained for up to 13 mm away from the implant. These findings suggest that the solidified alginate hydrogel material acts as a left ventricular mid-wall constraint that significantly reduces adverse LV remodeling compared to untreated heart failure controls without causing negative secondary outcomes to cardiac function. Moreover, if the hydrogel can be delivered percutaneously rather than via the currently used open-chest procedure, this therapy may become routine for heart failure treatment. A minimally invasive procedure would be in the best interest of this patient population; i.e., one that cannot tolerate general anesthesia and surgery, and it would be significantly more cost-effective than surgery.

Dataset Information

Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences.

Publications

Ventricular wall biomaterial injection therapy after myocardial infarction: Advances in material design, mechanistic insight and early clinical experiences.

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