Vascular graft can improves the lives of people with coronary artery disease and congenital cardiovascular defects


Researchers may be closer to improving the lives of people with coronary artery disease and children born with pediatric congenital cardiovascular defects through the development of a new vascular graft created by Johns Hopkins engineers that takes less than one week to make and has regenerative properties.

Coronary artery disease, or CAD, is the leading cause of death worldwide and people with the disease often require surgery to repair damaged cardiovascular tissue.

Bypass surgery, another common intervention, requires removing the damaged tissue and replacing it with blood vessels from another part of the body, such as the saphenous vein, which runs the length of the leg and is the longest vein in the body.

This method puts substantial stress on the body and has other risk factors: it requires patients to have multiple surgical sites, and those in need of the surgery because of plaque build-up may also have plaque accumulation in the grafted vein, causing further complications.

Congenital cardiovascular defects, or CCD, occurs in 1% of live births worldwide, and children born with the condition often undergo repeated surgical reconstruction as they grow.

But repeated surgeries reduce the amount of usable vascular tissue for reconstruction and synthetic grafts do not grow as the child grows.

Synthetic grafts pose other challenges such as clotting, which blocks blood flow, and grafts grown from stem cells often require up to eight weeks of preparation.

To improve surgical practices and reduce the number of surgeries a person with CAD and CCD may need, a vascular graft that encourages new tissue formation with better mechanical properties that mimic natural arteries is needed.

Sharon Gerecht, director of the Institute for NanoBioTechnology and a professor in the Department of Chemical and Biomolecular Engineering, and Morgan Elliott, a doctoral candidate in the Department of Biomedical Engineering, led a team of scientists in creating a natural graft that takes less than one week to prepare, dissolves as healthy tissue grows in its place, and can withstand the continuous contraction and relaxation cycle that the beating heart puts on arteries and veins.

“Our goal was to combine our patented electrospinning technology and stem cells to create a novel vascular graft that decreases fabrication time significantly, even more than grafts moving through clinical trials, while also decreasing clotting and enhancing tissue regeneration,” says Elliott.

A report of their findings was recently published their findings in the Proceedings of the National Academy of Sciences.

Their electrospinning process produces thin fiber threads by applying an electrical charge and mechanical pulling to the fibrin polymer.

The team chose fibrin for their graft because it is a natural polymer made by the body that prevents blood clotting, encourages new tissue formation, and increases elastin production.

Elastin is a critical protein in arteries that helps tissue retain its shape after stretching.

The sheets are then rolled in an alternating pattern to create a hollow tube, which is then dehydrated and stored for later use.

Once rehydrated, the graft’s exterior is reinforced with a poly(ε-caprolactone), or PCL, sheath to prevent sutures from tearing the graft.

From there, the team follows different preparatory steps before implanting the graft, depending on the patient’s needs.

For emergency needs, grafts can be implanted immediately after rehydration.

For patients with chronic vascular disease that know they will eventually need surgery, their stem cells can be collected and embedded on the graft before implantation.

In a mouse study, the team created small vascular grafts 0.6 mm in diameter and 3-5 mm long with and without stem cells and tested them in the abdominal aorta.

After 6 months, both graft types showed no evidence of clotting, no new tissue formed from inside the graft outward, and the grafts were able to maintain mechanical properties similar to healthy vasculature.

The grafts encouraged elastin production, which has typically been a challenge in the field. Importantly, it was found that the graft mediated regeneration and the stem cells enhanced the regeneration process.

Their positive results show that their graft technology has clinical and commercial potential, the researchers say.

The team plans to assess the graft’s shelf life and to test 5mm diameter grafts in larger animal models.

“This research is the result of a collaborative effort among five labs, combining expertise in stem cell engineering, biomaterials, surgery, vascular mechanics, and vascular disease.

The Maryland Stem Cell Research Fund, through their Validation grant mechanism, enabled us to advance the technology to pre-clinical studies.

We are committed to further developing our small-diameter vascular graft platform technology to benefit patients,” say Elliott and Gerecht.

Ischaemic heart disease is one of the major causes of death, disability and health care resource utilization worldwide.

As the population ages, an increasing number of elderly patients are undergoing surgical revascularization [1].

Elderly patients pose a significant challenge as they have a greater incidence of comorbidities impacting adversely on outcomes and thus experience higher morbidity and mortality.

Coupled with the unprecedented rise in the number of elderly patients presenting as potential surgical candidates, recent advances in operative techniques and perioperative care have resulted in an increasing number of elderly patients undergoing coronary artery bypass grafting (CABG) procedures [23].

CABG is very effective at relieving angina and improving survival, which are the primary indications for the operation.

Traditional outcome measures assessing the quality of CABG have been morbidity and mortality.

However, with improvements in perioperative care, cardiopulmonary bypass and surgical techniques, the overall mortality associated with CABG has declined despite an increasingly elderly and sicker patient cohort.

Furthermore, in an ever-aging elderly population in whom surgical intervention is more often of symptomatic rather than prognostic benefit, long-term mortality has limited use as an outcome measure.

Over recent years, there has been an increasing interest in assessing health-related quality of life (HRQOL), defined as a multi-dimensional assessment of an individual’s perception of the physical, psychological and social aspects of life that can be affected by a disease process and its treatment.

This increasing focus on the patient’s perspective has led to the development of Patient Reported Outcomes Measures (PROMS), outcomes that provide a validated evidence of health from the patient’s perspective [4].

The use of PROMs can greatly enhance the assessment of quality of care, particularly HRQOL, and have great potential to transform healthcare [5]. At present, there are three broad categories of PROMs instruments: (i) generic health status, (2) condition- or population-specific and, (iii) preference-based measures.

Generic health status measures (e.g. Short form [SF]-36, RAND SF-36, SF-20) aim to give a fully comprehensive assessment of HRQOL thus providing a common scoring system that may be used to compare different patient cohorts, conditions and subsequent treatments. In contrast, condition-specific measures (e.g. Seattle Angina Questionnaire [SAQ], Dukes Activity Status Index [DASI] and Rose Angina Questionnaire [RAS]) provide a precise score of health status for a given condition, rendering them more sensitive to smaller changes in HRQOL that may not be reflected in a general measures assessment [6].

Preference-based measures differ in that they provide an assessment of the effectiveness of a treatment or intervention to prevent disease based on HRQOL.

The outcomes of such scoring systems are often utilized in evaluating the cost-effectiveness or cost-benefit of a given treatment or procedure. Examples of such tools include the 15D-Measure of Health-related Quality of Life and EuroQOL-5D scoring systems [7].

As a consequence of the increasing elderly population undergoing cardiac surgery, data are needed to adequately counsel patients so that their expectations are aligned with their likely outcome, particularly in terms of improvements in quality of life.

In the elderly population, the assessment of quality of life after cardiac surgery has been recently appropriately described as ‘under researched research’ [8], with greater focus on mortality as a marker of surgical outcome. However, in this population where symptomatic rather than long-term prognostic improvement is more pertinent in defining operative success, HQOL may be a more important indicator of clinical outcome.

The aims of this study were to systematically review the published literature relating to HRQOL outcomes for elderly patients who have undergone CABG.

First, we assess the quality of studies within the literature, highlight the different tools used in assessing HRQOL and identify predictors of poor HRQOL.

Secondly, we perform comparative therapies assessment in terms of HRQOL in the elderly and demonstrate findings that confirm the potential benefits of CABG in elderly patients. Finally, we uncover the limitations of the current literature and formulate recommendations for much-needed future work in this area.

More information: Morgan B. Elliott et al. Regenerative and durable small-diameter graft as an arterial conduit, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1905966116

Journal information: Proceedings of the National Academy of Sciences
Provided by Johns Hopkins University


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