Biomedical Engineering Reference
In-Depth Information
32 CHAPTER 3.
IN VITRO
TISSUE ENGINEERING
to emulate these signals. It has been described that the objective of bioreactors is to create signals
reminiscent of the native environment, e.g., the 1 Hz pace of walking, the low oxygen tension
of the joint, and others. Unfortunately, the physiological conditions have been shown repeatedly
to result in cartilage degeneration, and, thus, the act of mimicking these conditions is now being
questioned. It may not be that non-physiological conditions are required, just that physiological
conditions of a different developmental period may be more beneficial in generating functional
cartilage. To investigate this latter case,
in vitro
tissue engineering has been employed to recapitulate
developmental conditions, in contrast to the
in vivo
tissue engineering efforts, which can only apply
adult conditions akin to the healing response.
3.1 THENEED FOR
IN VITRO
TISSUE ENGINEERING
The primary advantage of
in vitro
tissue engineering is proposed to be immediate functionality. A
tissue replacement that is mechanically and biologically functional before implantation will have a
higher probability for success. This is especially true for mechanically rigorous environments such
as articulating joints. Without the requisite mechanical characteristics, a tissue engineered construct
would be quickly destroyed by the normal loading of an ambulatory patient. However, the implan-
tation of a construct that possesses material properties comparable to the native tissue would not
fracture or degrade. Because of this, many researchers believe articular cartilage engineering should
place emphasis on construct development
in vitro
. Since the tissue resides in a mechanically demand-
ing environment, the implanted construct needs to be developed to a point that it can withstand
or respond to these mechanical loads. Constructs possessing insufficient integrity will collapse in
the articular defect, which not only prevents regeneration but could also accelerate degradation of
the tissues surrounding it. Efforts to heal large defects
in vivo
could fail without some means of
protecting the structure of newly developed tissues. By growing neocartilage in a laboratory, the
culture environment can be carefully controlled with respect to nutrient supply, biological stimuli,
and mechanical loading.
For a tissue like articular cartilage, possible treatments often depend on the type of damage
to the joint. For example, an osteochondral defect which reaches down into the subchondral bone
introduces blood into the system. This influx of blood and marrow brings a variety of chemicals and
cells to the injury site. However, fibrocartilage will form in the defects if left untreated, filling the
site with a disordered mass of fibrous tissue that possesses no long-term mechanical functionality.
Another type of damage in cartilage is termed a chondral defect and does not extend through the
depth of the tissue to reach vascularity. In this case, some of the chemical and biological variables
associated with osteochondral defects are not relevant. Unfortunately, the mechanical functionality is
still compromised due to disruption of the tissue's surface. Both osteochondral and chondral defects
can be considered focal defects since the damage is localized to a single region. The most difficult
type of cartilage injury to treat is a systemic breakdown of the articulating surface caused by diseases
such as OA and osteochondritis dissecans. Traditional tissue engineering approaches create small
constructs that can be fit into focal defect sites in the cartilage. However, this would be insufficient
