Mechanical
stimulation improves tissue engineered cartilage development both in terms of
biochemical composition and structural properties. However, the link between the
compositional changes attributed to mechanical stimulation and the changing
structural properties of the engineered cartilage is poorly understood. We
hypothesize that transient events associated with construct stiffening can be
documented and used to understand milestones in construct development. To do this we designed and
built a mechanical stimulation bioreactor that can continuously record the
force response of the engineered construct in real-time. This study
documents the transient
changes of the stiffness of tissue engineered cartilage constructs over the
first 14 days of their development under cyclic loading.
Compressive strain stimulation (15%,
1-Hz) was applied to
poly(ethylene-glycol) (PEG) hydrogels seeded with primary articular chondrocytes. The average compressive
modulus of strain stimulated constructs was
12.7 ± 1.45 kPa after 2 weeks, significantly
greater (p<0.01) than the average compressive moduli of both unstimulated
constructs (10.7 ± 0.94 kPa) and non-viable stimulated constructs (11.2 ± 0.91
kPa). The system was able to document that nearly all of the stiffness
increase occurred over the last two days
of the experiment, where live-cell constructs demonstrated a rapid
20% increase in force response. The systems ability to track significant
increases in stiffness over time was also confirmed by Instron® testing. These results present a novel view of the early
mechanical development of tissue engineering cartilage constructs and suggests
that the real-time monitoring of force response may be used to non-invasively
track the development of engineered tissue.
