Functional Tissue Engineering of Cartilage and Myocardium: Bioreactor Aspects

I. Introduction .................................................................................................................... 501

II. Tissue Engineering Bioreactors ..................................................................................... 503

III. Bioreactor Cultivation of Engineered Cartilage ............................................................ 507

A. Orbitally Mixed Dishes .......................................................................................... 507

B. Static Flasks, Mixed Flasks, Rotating Vessels, and Perfused Cartridges ............. 511

C. Mechanical Stimulation ......................................................................................... 511

D. Interactions of Growth Factors and Hydrodynamic

or Mechanical Stimulation ..................................................................................... 511

E. Controlled Bioreactor Studies ................................................................................ 512

IV. Bioreactor Cultivation of Engineered Cardiac Tissue .................................................. 513

A. Static and Orbitally Mixed Dishes ........................................................................ 513

B. Mixed Flasks .......................................................................................................... 514

C. Rotating Vessels ..................................................................................................... 515

D. Perfused Cartridges with Interstitial Flow of Medium ......................................... 515

E. Mechanical Stimulation ......................................................................................... 516

F. Electrical Stimulation ............................................................................................. 517

V. Case Studies ................................................................................................................... 517

VI. Summary ........................................................................................................................ 526

Acknowledgments ...................................................................................................................... 526

References ................................................................................................................................... 526

Tissue engineering combines the principles of biology, engineering, and medicine to create

functional grafts capable of repairing native tissue following a congenital deformity, disease, or

trauma. Engineered tissues can provide high-fidelity models for basic studies of cell function and

tissue development, and responses to genetic alterations, drugs, hypoxia, and physical stimuli. The

overall objective of tissue engineering is the restoration of normal tissue function. Ideally, lost or

damaged tissue should be replaced by an engineered graft that can reestablish appropriate structure,

composition, cell signaling, and key function(s) of the native tissue. In light of this paradigm, the

clinical utility of tissue engineering will likely depend on our ability to replicate the site-specific

properties of the tissue being replaced across different size scales and establish the specific

differentiated cell phenotype, the composition, architectural organization, and biomechanical

properties of the extracellular matrix (ECM), and provide the continuity and strength of the

interface with the neighboring host tissues.