Showing 5 ideas for tag "tissue"

Goal 2: Reduce Human Disease

Durable Tissue-Engineered Cardiac Valves

For replacement valves to achieve durable success, what are the best cell type(s), scaffold design, imaging approaches, and scalable manufacturing approaches?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Successfully meeting this challenge would lead to replacement heart valves that would not require lifelong anticoagulant medication. For younger patients, it would also eliminate revision surgeries as the implanted valves would grow with the patient over time.

Feasibility and challenges of addressing this CQ or CC

Tissue engineered valves have already been developed, but their durability must be increased. Cues can be drawn from the successes of other engineered tissues where long-term mechanical strength has been achieved.
Currently, valve replacement utilizes prosthetic and bio prosthetic materials. However, tissue engineered valves offer the prospect of living cardiovascular tissue substitutes in order to overcome the shortcomings of current prosthetic and bioprosthetic materials. Early prototypes have demonstrated satisfactory initial function, but competence deteriorates over time. Initial clinical demonstrations could target the right side of the circulation, such as the pulmonary valve in patients with congenital defects and the repair of the tricuspid valve, since these applications lack catastrophic hemodynamic consequences for valve failure.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 2: Reduce Human Disease

How can we better understand regional tissue heterogeneity in lung disease?

Many lung diseases (IPF, COPD) are characterized by marked heterogeneity at the tissue level. Unfortunately, most of the tools we currently employ to understand lung disease are unable to elucidate the mechanisms that result in regional heterogeneity. Clinical studies and animal models, while invaluable, generally assume that all lung tissue is similarly affected based on the presence or absence of diagnostic criteria... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Emerging evidence suggests that diseases such as IPF and COPD have observable phenotypes at the cellular and tissue levels long before the disease is clinically apparent. Thus seemingly healthy patients may have some regions of the lung affected by the same pathophysiologic processes that drive clinically apparent disease. By changing the focus of investigation from the presence or absence of disease in a given patient to the presence of absence of disease in a given region, several advantages emerge: (1) pathophysiologic mechanisms may be investigated earlier in the natural history of a disease, when interventions are more likely to be of benefit; (2) early investigation favors the discovery of distinct disease subgroups that are masked in more severe disease; and (3) a single patient may provide multiple affected and unaffected disease regions, allowing him or her to serve as their own control. Recently, advances in next-generation sequencing have made it possible for the entire transcriptome of a single cell to be analyzed. It is reasonable to believe that in the next 10 years single cell epigenome, proteome, and metabolome profiling will become routine. However, it seems less obvious how these methodologies can be employed to better understand the drivers of regional differences in lung disease. While technically difficult, studies applying high-throughput technologies to the discovery of regional differences will be invaluable to our understanding of lung disease.

Feasibility and challenges of addressing this CQ or CC

To address this critical challenge, at least five technological hurdles will have to be addressed: (1) technologies such as laser capture microdissection which allow for the isolation or cells from specific areas of the lung will need to improve; (2) technologies allowing for culture of multiple cell types on a single artificial substrate (to allow for experimental manipulation of cellular “communities”) will need to emerge; (3) collaborative networks will need to emerge whereby datasets from multiple labs can be integrated; (4) bioinformatics and statistical methods capable of filtering massive “omics” data sets from multiple cell types will need to be refined; and (5) researchers with the skills necessary to distil large descriptive datasets into testable hypotheses will need to be trained. While these hurdles are great, they must be overcome in order to translate the promise of next-generation sequencing techniques into an improved understanding of the drivers of regional heterogeneity in lung disease.

Name of idea submitter and other team members who worked on this idea Bradley Richmond

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26 up votes
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Goal 3: Advance Translational Research

NHLBI Cardiovascular Engineering Strategy

Most impressive and impactful advances in CV diagnostics and therapies came in the last 50 years from CV engineering, including implantable devices and imaging technology. CV engineers are developing next breakthrough technology including tissue engineering and flexible electronics. However, organizational structure of NIH does not have an entity responsible for strategic development of CV engineering. NIBIB does not... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

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Cardiovascular Science produced numerous fundamental ideas, which frame our approaches to diagnostics and therapy of heart disease. However, translating these ideas to clinic very often requires engineering approaches. Examples of such breakthrough therapies are implantable pacemakers and defibrillators, stents, MRI, CT and many other imaging modalities. NIBIB supports many fields of biomedical engineering, except cardiovascular! NHLBI lacks a branch responsible for strategic development of cardiovascular engineering as a critical pathway to translation of basic science ideas. There is no study section or review group focusing on cardiovascular engineering. As a result, most of CV Engineering grants are reviewed by CV biologists, who lack engineering background and have quite different priorities and vision of the field. Next breakthrough developments will happen in tissue engineering, flexible/stretchable/biodegradable electronics, novel imaging modalities, computational physiology, and other classical biomedical engineering sub-fields. Unfortunately, they are less likely to happen in cardiovascular field, because NHLBI lacks corresponding organizational structure. A working group should be formed to frame NHLBI's vision for the future of cardiovascular engineering as an indispensable component for translation from CV biology to CV therapy.

Feasibility and challenges of addressing this CQ or CC

Biomedical engineering has trained several generations of professionals in academia and industry, which pursue basic and translational research and development with great degree of success. CV Engineering is a standard component in numerous BME Departments. Large number of senior and junior CV engineers have been recognized for their significant contribution to CV health. There is enormous CV engineering expertise and experience, which should be leveraged by NHLBI, in order to broadly define institutional strategy not only for CV biology but also for CV engineering, which are equally important in development of future breakthrough therapies for CV disease. Currently, support for CV engineering is scattered across numerous mostly biology focused groups, lacking strategic vision and coherent policy. A number of talented CV engineers are forced to leave the field to pursue other areas of biomedical engineering, which enjoy better-organized professional group support.

Name of idea submitter and other team members who worked on this idea Igor Efimov

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Goal 3: Advance Translational Research

Tissue engineered constructs for vascular disease

Can we develop improved, clinically effective tissue engineered constructs for vascular disease?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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We need a better alternative to coronary and lower extremity bypass surgery for patients lacking adequate vein.

Name of idea submitter and other team members who worked on this idea Society for Vascular Surgery

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Goal 3: Advance Translational Research

Personalized Medicine thru CV bioinformation/tissue repository

There is a need to establish virtual CV biologic tissues and a bioinformational repository for specific CV diseases, including congenital cardiovascular malformations, genetic or other unique cardiomyopathies, such as stress cardiomyopathy and giant cell myocarditis.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Personalized medicine promises patient-tailored management enhancing patient care and decreasing overall treatment costs by focusing on genetics/omics data obtained from patient biospecimens and electronic medical records (EMR) to guide therapy that generate optimal clinical outcomes. The approach relies on diagnostic and prognostic use of novel biomarkers discovered through combinations of tissue banking, bioinformatics, and electronic medical records. The analytical power of bioinformatic platforms combined with patient clinical data from EMRs can reveal potential biomarkers and clinical phenotypes that allow researchers to develop experimental strategies using selected patient biospecimens stored in tissue banks.

Feasibility and challenges of addressing this CQ or CC

the repository would utilize high quality biospecimens in concert with reliable EMR collected at diagnosis and through various treatment stages to provide crucial resources help identify a new risk factors and to facilitate development of novel therapies. The data obtained would also require cross-disciplinary collaborations to translate experimental results into clinical practice and diagnostic and prognostic use in personalized medicine. The repository focus would be on the discovery of predictive, diagnostic, and prognostic biomarkers that will allow proper diagnosis of specific CV diseases, increase information about a particular disease, and indicate the direction treatment should take.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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