Biomedical Engineering Reference
In-Depth Information
CHAPTER
4
Bioreactors
Articular cartilage is a mechanically-sensitive tissue that can respond favorably or unfavorably to
biomechanical stimuli. The results from experimental studies included in this section combine many
different approaches for enhancing cartilage regeneration. However, direct comparisons are difficult
due to the variety of cell sources, media cocktails, and general laboratory practices used from study
to study. In general, cell-seeded scaffolds, or “constructs,” are cultured in vitro to help produce a
neo-tissue that has sufficient mechanical and/or biochemical properties for implantation.
Although the precise signaling pathways involved in the mediation of mechanostimuli are
not completely understood, evidence suggests that certain types of forces are desirable for cartilage
synthesis and modeling. Under static conditions, chondrocytes synthesize a material that has poor
tissue organization [ 459 ]. Since static culture conditions appear to be inadequate, dynamic culture
conditions have been studied extensively for their beneficial effects on cartilage synthesis and orga-
nization. The creation of cartilaginous material in bioreactors has proven to be successful and is a
promising means to obtain reproducible tissue constructs [ 353 , 459 ]. In general, the composition,
morphology, and mechanical properties of cartilage synthesized in a bioreactor appear better than
cartilage grown under static conditions [ 460 ].
This section includes descriptions of past and current bioreactors used for stimulating cartilage
explants or engineered constructs (Figure 4.1). The categories included in this chapter's review of
biomechanical stimulation include:
￿ Direct compression.
￿ Hydrostatic pressure.
￿ Shear bioreactors (surface/fluid-surface shearing, direct flow and fluid perfusion, low-shear
“microgravity” bioreactors).
￿ “Low-shear” systems (enhanced nutrient transport, “microgravity” bioreactors).
￿ Hybrid bioreactors incorporating multiple loading regimes.
4.1 DIRECT COMPRESSION
Compressive loading is a major component of normal mechanical stimulation within diarthrodial
joints. The points of contact between the femoral condyle and the tibial plateau (and intervening
menisci) cause compression within the cartilage tissue that is separate from other types of mechanical
stimulation. Studies focusing on direct compression typically use platens that physically touch the
construct surface. Static or dynamic loading with these devices mechanically deforms the sample.
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