ReviewTissue engineering solutions to replace contractile function during pediatric heart surgery
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)
- et al.
Engineered heart tissue models from hiPSC-derived cardiomyocytes and cardiac ECM for disease modeling and drug testing applications
Acta Biomater.
(2019) - et al.
Novel bench-top perfusion system improves functional performance of bioengineered heart muscle
J. Biosci. Bioeng.
(2009) - et al.
Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells
Biomaterials.
(2018) - et al.
Replacement of ventricular myocardium with diaphragmatic skeletal muscle: short-term studies
J. Thorac. Cardiovasc. Surg.
(1981) - et al.
Cardiovascular disease models: a game changing paradigm in drug discovery and screening
Biomaterials.
(2019) - et al.
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors
Cell
(2006) - et al.
Selective cell transplantation using bioabsorbable artificial polymers as matrices
J. Pediatr. Surg.
(1988) - et al.
Inkjet printing of viable mammalian cells
Biomaterials.
(2005) - et al.
Excitation propagation in three-dimensional engineered hearts using decellularized extracellular matrix
Biomaterials
(2014) - et al.
A highly conductive 3D cardiac patch fabricated using cardiac myocytes reprogrammed from human adipogenic mesenchymal stem cells
Cardiovasc. Eng. Technol.
(2020)
Future challenges in the in vitro and in vivo evaluation of biomaterial biocompatibility
Regen. Biomater.
Skeletal muscle as a myocardial substitute
Proc. Soc. Exp. Biol. Med.
Self-organization of rat cardiac cells into contractile 3-D cardiac tissue
FASEB J.
Norwood procedure for palliation of hypoplastic left heart syndrome: right ventricle to pulmonary artery conduit vs modified blalock-taussig shunt
Crit. Care Nurse
3D bioprinting and its potential impact on cardiac failure treatment: an industry perspective
APL Bioeng.
Myocardial engineering in vivo: formation and characterization of contractile, vascularized three-dimensional cardiac tissue
Tissue Eng.
In vivo conditioning of tissue-engineered heart muscle improves contractile performance
Artif. Organs
Development of a novel bioreactor for the mechanical loading of tissue-engineered heart muscle
Tissue Eng.
Force characteristics of in vivo tissue-engineered myocardial constructs using varying cell seeding densities
Artif. Organs
Effect of streptomycin on the active force of bioengineered heart muscle in response to controlled stretch
In Vitro Cell. Dev. Biol. Anim.
Design and fabrication of heart muscle using scaffold-based tissue engineering
J. Biomed. Mater. Res. A.
Digital design and 3D printing of aortic arch reconstruction in HLHS for surgical simulation and training
World J. Pediatr. Congenit. Heart Surg.
Pediatric heart transplantation in the current era
Curr. Opin. Pediatr.
Hypoplastic left heart syndrome: a review
Acta Med. Litu.
Hypoplastic left heart syndrome: current perspectives
Transl. Pediatr.
Hypoplastic left heart syndrome: a new paradigm for an old disease?
J. Cardiovasc. Dev. Dis.
Bioengineering human myocardium on native extracellular matrix
Circ. Res.
Engineering the heart piece by piece: state of the art in cardiac tissue engineering
Regen. Med.
Development of a microperfusion system for the culture of bioengineered heart muscle
ASAIO J.
Generation of spatial-patterned early-developing cardiac organoids using human pluripotent stem cells
Nat. Protoc.
Contractile three-dimensional bioengineered heart muscle for myocardial regeneration
J. Biomed. Mater. Res. A.
Modulating the functional performance of bioengineered heart muscle using growth factor stimulation
Ann. Biomed. Eng.
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.
Effect of thyroid hormone on the contractility of self-organized heart muscle
In Vitro Cell. Dev. Biol. Anim.
Changes in gene expression during the formation of bioengineered heart muscle
Artif. Organs
Micro-perfusion for cardiac tissue engineering: development of a bench-top system for the culture of primary cardiac cells
Ann. Biomed. Eng.
Getting to the heart of tissue engineering
J. Cardiovasc. Transl. Res.
Variable optimization for the formation of three-dimensional self-organized heart muscle
In Vitro Cell. Dev. Biol. Anim.
Biomaterial and stem cell interactions: histological biocompatibility
Curr. Stem Cell Res. Ther.
Engineered cardiac organoid chambers: toward a functional biological model ventricle
Tissue Eng. Part A
3D bioprinting of collagen to rebuild components of the human heart
Science
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