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EMT-Inducing Biomaterials for Heart Valve Engineering: Taking Cues from Developmental Biology

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Abstract

Although artificial prostheses for diseased heart valves have been around for several decades, viable heart valve replacements have yet to be developed due to their complicated nature. The majority of research in heart valve replacement technology seeks to improve decellularization techniques for porcine valves or bovine pericardium as an effort to improve current clinically used valves. The drawback of clinically used valves is that they are nonviable and thus do not grow or remodel once implanted inside patients. This is particularly detrimental for pediatric patients, who will likely need several reoperations over the course of their lifetimes to implant larger valves as the patient grows. Due to this limitation, additional biomaterials, both synthetic and natural in origin, are also being investigated as novel scaffolds for tissue-engineered heart valves, specifically for the pediatric population. Here, we provide a brief overview of valves in clinical use as well as of the materials being investigated as novel tissue-engineered heart valve scaffolds. Additionally, we focus on natural-based biomaterials for promoting cell behavior that is indicative of the developmental biology process that occurs in the formation of heart valves in utero, such as epithelial-to-mesenchymal transition or transformation. By engineering materials that promote native developmental biology cues and signaling, while also providing mechanical integrity once implanted, a viable tissue-engineered heart valve may one day be realized. A viable tissue-engineered heart valve, capable of growing and remodeling actively inside a patient, could reduce risks and complications associated with current valve replacement options and improve overall quality of life in the thousands of patients who received such valves each year, particularly for children.

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Abbreviations

BMP2:

Bone morphogenic protein 2

ES:

Electrospun

EPC:

Endothelial/epithelial progenitor cell

EMT:

Epithelial-to-mesenchymal transition or transformation

ePTFE:

Expanded poly(tetraflouroethylene)

ECM:

Extracellular matrix

FDM:

Fused deposition modeling

GAG:

Glycosaminoglycan

HA:

Hyaluronic acid

MMP:

Matrix metalloproteinase

MSC:

Mesenchymal stem cell

MEKK3:

Mitogen-activated protein 3 kinase

PEUU:

Poly(ester urea urethane)

PEG:

Poly(ethylene glycol)

PGS:

Poly(glycerol sebacate)

PGA:

Poly(glycolic acid)

PLA:

Poly(lactic acid)

P4HB:

Poly-4-hyrdoxybutyrate

PCL:

Polycaprolactone

PCU:

Polycarbonate

PDO:

Polydioxaneone

POSS:

Polyhedral oligomeric silsesquioxanes

TPU:

Thermoplastic polyurethane

TGF-β1:

Transforming growth factor β1

TGF-β2:

Transforming growth factor β2

VEC:

Valvular endothelial cell

VIC:

Valvular interstitial cell

VEGF:

Vascular endothelial growth factor

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Acknowledgments

YWC was supported by NIH Common Fund grants (EB008539 and HL092551). AK was supported by NIH (DE019024, HL092836, and HL099073). WDM was supported by the American Heart Association (0835496N and 09GRNT2010125), Wallace H. Coulter Foundation (Early Career Award), NSF (1055384), and NIH (HL094707).

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Authors and Affiliations

  1. Department of Biomedical Engineering, Vanderbilt University, Room 9445D MRB IV-Langford, 2213 Garland Avenue, Nashville, TN, 37232-0493, USA

    M. K. Sewell-Loftin, Young Wook Chun & W. David Merryman

  2. Center for Biomedical Engineering, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, 02139, USA

    Ali Khademhosseini

  3. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

    Ali Khademhosseini

  4. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA

    Ali Khademhosseini

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  1. M. K. Sewell-Loftin
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  2. Young Wook Chun
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  3. Ali Khademhosseini
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  4. W. David Merryman
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Correspondence to W. David Merryman.

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Sewell-Loftin, M.K., Chun, Y.W., Khademhosseini, A. et al. EMT-Inducing Biomaterials for Heart Valve Engineering: Taking Cues from Developmental Biology. J. of Cardiovasc. Trans. Res. 4, 658–671 (2011). https://doi.org/10.1007/s12265-011-9300-4

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