Elsevier

Tissue and Cell

Volume 67, December 2020, 101452
Tissue and Cell

Review
Tissue engineering solutions to replace contractile function during pediatric heart surgery

https://doi.org/10.1016/j.tice.2020.101452Get rights and content

Highlights

  • Pediatric heart sugery remains challenging.

  • New tools are needed to tackle this enormous challenge.

  • Bioengineered heart muscle, ventricles, Fontan pumps and hearts can be used in pediatric heart surgery.

  • This technology can prove to be game-changer in the field of pediatric heart surgery.

Abstract

Pediatric heart surgery remains challenging due to the small size of the pediatric heart, the severity of congenital abnormalities and the unique characteristics of each case. New tools and technologies are needed to tackle this enormous challenge. Tissue engineering strategies are focused on fabricating contractile heart muscle, ventricles, Fontan pumps and whole hearts, and a transplantable tissue equivalent has tremendous implications in pediatric heart surgery to provide functional cardiac tissue. This technology will prove to be a game-changer in the field of pediatric heart surgery and provide a novel toolkit for pediatric heart surgeons. This review will provide insight into the potential applications of tissue engineering technologies to replace lost contractile function in pediatric patients with heart abnormalities.

Section snippets

Introduction to tissue engineering

The scarcity of donor organs is widely known and with a large gap between available donor organs and the number of patients in need of a solid organs for transplant. The situation is worsening with improvements in medical care making more people candidates for transplant and fewer donor hearts available for transplant. Pediatric heart transplantation is faced with the same challenges as seen in the adult population, which include the risk of rejection, need for immunosuppression therapy and the

Stem cells in tissue engineering

The building blocks of tissue engineering are cells – both stem and regenerative (Islas et al., 2020), biomaterials (Blan and Birla, 2008) and bioreactors (Hecker and Birla, 2007; Birla et al., 2007).

Stem and regenerative cells are obtained from patients, with dermal fibroblasts being one common example, reprogrammed to form induced pluripotent stem cells (iPSCs) and then differentiated to form any cell type in the human body (Birla and Williams, 2020) (Fig. 1B). This technology is the basis of

Biomaterials in tissue engineering

Biomaterials simulate the mammalian extracellular matrix (ECM), the glue that binds all cells together to form functional tissue together. Biomaterials are tailor fabricated to match the functional requirements for any given tissue or organ systems, based on mechanical properties, biocompatibility, biomimetic properties and degradation kinetics (Fig. 1C) (Blan and Birla, 2008). Mechanical properties refer to the mechanical stability of the biomaterial, quantified using the Young’s modulus (

Bioreactors in tissue engineering

The human heart is a very complex organ and constant changes in the physiological environment are critical determinants of function and cardiac output. CMs are the workhorse of human hearts and are responsible for the contractile function. CMs are dynamic cells and respond to local changes in mechanical stress, electrical impulses resulting from the depolarization wave and the complex chemical environment consisting of growth factors, hormones and cytokines. Bioreactors are custom devices

Fabrication technologies in tissue engineering

There are multiple biofabrication technologies in place to support tissue and organ fabrication, with bioprinting (Birla and Williams, 2020) and the use of acellular scaffolds (Tao et al., 2015) being two examples. Bioprinting is a technology based on additive manufacturing technologies that include commercial inkjet printers (Xu et al., 2005) and pneumatic pressure, direct-write technologies (Smith et al., 2004) to extrude a bioink consisting of cells and biomaterials, using a set of

Tissue engineering for the heart

Tissue engineering is a very expansive field, the applications of tissue engineering are very broad and recent efforts have included almost all tissues and organ systems in the human body. The cardiovascular system has been an area of interest for some time and there are now several seminal publications demonstrating the fabrication of whole hearts and components of the heart, including heart muscle patches (Wu and Guo, 2018; Vozzi et al., 2018; Valarmathi et al., 2018), left ventricles (Lee et

Tissue engineering in pediatric heart surgery

Hypoplastic left heart syndrome (HLHS) is a congenital condition which annually occurs in approximately 960 births in the US (Saraf et al., 2019). Pediatric patients with HLHS are born with an underdeveloped left ventricle (LV) and the condition also affects many other structures on the left side of the heart (Fig. 2A–B). The Congenital Heart Surgery Nomenclature and Database Committee has defined HLHS as “HLHS is a spectrum of cardiac malformations, characterized by a severe underdevelopment

Heart muscle tissue engineering

Introducing to Heart Muscle Tissue Engineering – the goal is to bioengineer 3D cardiac patches that can be used to replace and/or augment the contractile function of diseased myocardium tissue (Tao et al., 2018; Birla et al., 2008a; Blan and Birla, 2008; Salazar et al., 2015a; Mohamed et al., 2017; Hecker et al., 2009; Khait and Birla, 2008; Huang et al., 2008; Nguyen et al., 2019; Abbasgholizadeh et al., 2020; Tao et al., 2017; Sondergaard et al., 2010; Khait et al., 2009; Khait and Birla, 2009

Ventricle tissue engineering

The goal is to bioengineer organoids that recreate the structure, anatomy and function of the mammalian left ventricle. The potential clinical application is in the treatment of cases of HLHS, a pediatric condition where the patient is born with an underdeveloped left ventricle (Roeleveld et al., 2018). Functional augmentation of HLHS patients with bioengineered ventricles may provide a novel interventional strategy for these patients. The vision is to obtain a patient derived stem cells and

Biological pumps

Pediatric patients with HLHS undergo a series of three surgical reconstructions, the last of which is the Fontan Procedure, during which the IVC is attached to the pulmonary circulation. The purpose of this surgical procedure is to create a pathway for the flow of blood from the right ventricle directly to the lungs, where it can be oxygenated prior to being delivered to the body. Current state of the art is to use a synthetic tubular graft, commonly made from expanded polytetrafluoroethylene

Whole heart bioengineering

Pediatric heart transplantation is a major challenge due to the scarcity of donor organs (D’Addese et al., 2019); the donor organ problem is well-known in the adult population and less discussed in the pediatric population. However, many of the problems that are known in the adult heart transplant population are also prevalent in the pediatric heart transplantation population. In the case of pediatric heart transplantation, there is a 20 % mortality rate while on the waiting list and the need

Animal models in cardiac tissue engineering

Bioengineered patches and biological pumps have been tested in animal models, discussed here. Bioengineered ventricles and whole hearts have not tested in animals.

Bioengineered patches are commonly tested in rats using a coronary ligation model to induce myocardial infarction (Valarmathi et al., 2018). The rat model is preferred over mice, due to the larger surface area of the heart in rats which provides more landscape for patch implantation studies. In patch implantation studies, the coronary

Summary and future perspective

Pediatric heart surgery remains challenging. Every case is unique and different and requires different reparative strategies. The pediatric heart surgeon is faced with a challenging task of operating on very small hearts with severe developmental abnormalities. New tools need to be developed to equip the pediatric heart surgeon with novel treatment options to tackle these very complex surgical scenarios. Tissue engineering strategies are designed to bioengineer 3D cardiac patches, ventricles,

References (82)

  • J.M. Anderson

    Future challenges in the in vitro and in vivo evaluation of biomaterial biocompatibility

    Regen. Biomater.

    (2016)
  • L.I. Astra et al.

    Skeletal muscle as a myocardial substitute

    Proc. Soc. Exp. Biol. Med.

    (2000)
  • K. Baar et al.

    Self-organization of rat cardiac cells into contractile 3-D cardiac tissue

    FASEB J.

    (2005)
  • D.M. Beke

    Norwood procedure for palliation of hypoplastic left heart syndrome: right ventricle to pulmonary artery conduit vs modified blalock-taussig shunt

    Crit. Care Nurse

    (2016)
  • R.K. Birla et al.

    3D bioprinting and its potential impact on cardiac failure treatment: an industry perspective

    APL Bioeng.

    (2020)
  • R.K. Birla et al.

    Myocardial engineering in vivo: formation and characterization of contractile, vascularized three-dimensional cardiac tissue

    Tissue Eng.

    (2005)
  • R.K. Birla et al.

    In vivo conditioning of tissue-engineered heart muscle improves contractile performance

    Artif. Organs

    (2005)
  • R.K. Birla et al.

    Development of a novel bioreactor for the mechanical loading of tissue-engineered heart muscle

    Tissue Eng.

    (2007)
  • R. Birla et al.

    Force characteristics of in vivo tissue-engineered myocardial constructs using varying cell seeding densities

    Artif. Organs

    (2008)
  • R.K. Birla et al.

    Effect of streptomycin on the active force of bioengineered heart muscle in response to controlled stretch

    In Vitro Cell. Dev. Biol. Anim.

    (2008)
  • N.R. Blan et al.

    Design and fabrication of heart muscle using scaffold-based tissue engineering

    J. Biomed. Mater. Res. A.

    (2008)
  • S.A. Chen et al.

    Digital design and 3D printing of aortic arch reconstruction in HLHS for surgical simulation and training

    World J. Pediatr. Congenit. Heart Surg.

    (2018)
  • L. D’Addese et al.

    Pediatric heart transplantation in the current era

    Curr. Opin. Pediatr.

    (2019)
  • R. Gobergs et al.

    Hypoplastic left heart syndrome: a review

    Acta Med. Litu.

    (2016)
  • C.E. Greenleaf et al.

    Hypoplastic left heart syndrome: current perspectives

    Transl. Pediatr.

    (2016)
  • P. Grossfeld et al.

    Hypoplastic left heart syndrome: a new paradigm for an old disease?

    J. Cardiovasc. Dev. Dis.

    (2019)
  • J.P. Guyette et al.

    Bioengineering human myocardium on native extracellular matrix

    Circ. Res.

    (2016)
  • L. Hecker et al.

    Engineering the heart piece by piece: state of the art in cardiac tissue engineering

    Regen. Med.

    (2007)
  • L. Hecker et al.

    Development of a microperfusion system for the culture of bioengineered heart muscle

    ASAIO J.

    (2008)
  • P. Hoang et al.

    Generation of spatial-patterned early-developing cardiac organoids using human pluripotent stem cells

    Nat. Protoc.

    (2018)
  • Y.C. Huang et al.

    Contractile three-dimensional bioengineered heart muscle for myocardial regeneration

    J. Biomed. Mater. Res. A.

    (2007)
  • Y.C. Huang et al.

    Modulating the functional performance of bioengineered heart muscle using growth factor stimulation

    Ann. Biomed. Eng.

    (2008)
  • J.F. Islas et al.

    Beta-Adrenergic stimuli and rotating suspension culture enhance conversion of human adipogenic mesenchymal stem cells into highly conductive cardiac progenitors

    J. Tissue Eng. Regen. Med.

    (2020)
  • L. Khait et al.

    Effect of thyroid hormone on the contractility of self-organized heart muscle

    In Vitro Cell. Dev. Biol. Anim.

    (2008)
  • L. Khait et al.

    Changes in gene expression during the formation of bioengineered heart muscle

    Artif. Organs

    (2009)
  • L. Khait et al.

    Micro-perfusion for cardiac tissue engineering: development of a bench-top system for the culture of primary cardiac cells

    Ann. Biomed. Eng.

    (2008)
  • L. Khait et al.

    Getting to the heart of tissue engineering

    J. Cardiovasc. Transl. Res.

    (2008)
  • L. Khait et al.

    Variable optimization for the formation of three-dimensional self-organized heart muscle

    In Vitro Cell. Dev. Biol. Anim.

    (2009)
  • P. Korkusuz et al.

    Biomaterial and stem cell interactions: histological biocompatibility

    Curr. Stem Cell Res. Ther.

    (2016)
  • E.J. Lee et al.

    Engineered cardiac organoid chambers: toward a functional biological model ventricle

    Tissue Eng. Part A

    (2008)
  • A. Lee et al.

    3D bioprinting of collagen to rebuild components of the human heart

    Science

    (2019)
  • Cited by (3)

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