Biomimetic Approach to Cardiac Tissue Engineering:

Biomimetic Approach to Cardiac Tissue Engineering:
Oxygen Carriers and Channeled Scaffolds

MILICA RADISIC, Ph.D.,1 HYOUNGSHIN PARK, Ph.D.,2 FEN CHEN, M.D.,2 JOHANNA E.
SALAZAR-LAZZARO, B.S.,2 YADONG WANG, Ph.D.,3 ROBERT DENNIS, Ph.D.,4 ROBERT
LANGER, Sc.D.,2 LISA E. FREED, M.D., Ph.D.,2 and GORDANA VUNJAK-NOVAKOVIC, Ph.D.5

Summary:

Objective:

The goal of this paper is to improve the engineered cardiac muscle by focusing on 2 factors: oxygen-carrier medium with PFC (perfluorocarbon) and channeled scaffold.

Background:

In vascularized tissues, e.g. myocardium, oxygen is supplied by convection of blood through a capillary network and diffusion into the tissue space surrounding each capillary. Under physiology condition, oxygen dissolved in blood plasma accounts for only 1.5% of total oxygen content of the blood. The majority comes from hemoglobin, a natural oxygen carrier that ensures that sufficient oxygen is supplied to the tissue at low flow rate (Re=1).

Native myocardium consists of several cell types: 1/3 myocytes (for ventricular contraction) and ~ 2/3 fibroblasts (for secreting components of ECM and transmitting mechanical force). Tissue constructs, based on passaged human pediatric heart cells contained a newly synthesized collagen network, illustrates the importance of fibroblasts in remodeling scaffold in vitro. However, in all previous studies, oxygen transport thru the tissue was largely governed by molecular diffusion which can support only a thin (100-200mm) surface layer of functional tissue and leaves the interior construct hypoxic and acellular.

Methods:

- To mimic the capillary network: cells were cultured on highly porous elastic polymer scaffold with parallel array of channels. (Coculture: myocytes were cultured on scaffolds pretreated with fibroblast).

- To mimic role of hemoglobin: channel array was perfused with synthetic oxygen carrier: PFC (PFC droplets are immiscible witht eh aqueous phase, they serve as rechargeable oxygen reservoir).

Results:

- Scaffold pretreatment with fibroblasts improved functional and biochemical properties of biorubber- based constructs cultivated in orbital dishes. The pretreated- biorubber constructs were either comparable or superior to the collagen-based construct.

- Effect of PFC emulsion on fibroblasts and cardiomyocytes: cellmorphology and viability were comparable for PFC supplemented and unsupplemented medium for both cell types.

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Conclusion

A biomimetic culture system was developed; in which cardiac fibroblasts and myocytes are cocultured on scaffoleds with parallel channel array that mimics the role of a capillary network perfused at a flow velocity of 500 mm/s (comparable to heart blood flow) with the culture medium supplemented with a PFC oxygen carrier that mimics the role of hemoglobin. Although the supplementation of PFC emulsion doubled the total oxygen content of culture medium, it remained significantly lower than oxygen content of whole blood. The increase in oxygen content in the PFC group enhanced cell density and DNA content, the amounts of cardiac proteins, and contractile properties of tissue constructs as compared to those measured for the unsupplemented (control) group.

Significance:

Engineered cardiac muscle has always been the top interest in tissue engineering. This paper provides an insight into how to improve the activity of artificial cardiac muscle, also gives another step in making artificial heart. Both the orientation of scaffold and appropriate medium are important in order to make the muscle as efficient as the real one. This research gave me ideas and background support for my project, which might be on cultivation of biomimetic cardiac myocytes and fibroblasts on channel scaffold.