A hydrogel
scaffold system with tunable bioactivity and a mechanical stimulation
bioreactor were used for cartilage tissue engineering with the motivation of
understanding the importance of scaffold bioactivity in chondrocyte response to
dynamic stimulation. Protein and proteoglycans were conjugated to
functionalized poly(ethylene glycol) (PEG) and immobilized in a PEG hydrogel to
create bio-synthetic materials. Four different bio-synthetic compositions were
tested in this study, including: PEG-Proteoglycan (PP), PEG-fibrinogen (PF),
PEG-Albumin (PA), and PEG only. The PP and PF represented the instructive
hydrogels which contained cell-adhesive ECM proteins for cell signaling; the PA
and PEG only represented the permissive hydrogels. The influence of the
bioactive elements of the scaffold was investigated under large strain
deformations (15%, at 1 Hz) of chondrocyte-seeded constructs for up to 28 days.
Mechanical stimulation had a beneficial effect on the chondrocyte response as
measured by the compressive modulus of the constructs, cell number,
glycosaminoglycans (GAGs) and collagen type II accumulation inside the
constructs. The composition of the scaffold significantly affected this
response, except for cell number. Stimulation also inhibited the production of
collagen type I, an indicator for chondrocyte de-differentiation. Swelling
ratio of the constructs decreased due to the stimulation and cell viability
remained high in all scaffold types. Correlation maps between scaffold
properties underscore the differences between permissive and instructive
scaffolds in this regard. These findings indicate that while dynamic stimulation
causes metabolic changes in chondrocytes seeded in PEG hydrogels, the matrix
bioactivity has a significant role in chondrocyte mechanotransduction. In order
to examine the mechanisms underlying remodeling, adaptation and degeneration of
neo-cartilage subjected to dynamic loads, it is also important to know the
stress-strain state in the encapsulated chondrocytes. In this context, a finite
element analysis of chondrocyte compression was performed using several
constitutive models to simulate the mechanical behavior of the different cell
embedded scaffolds and to describe the stress-strain state in the chondrocytes
during unconfined compression. Material modulus, cell size and pericellular
matrix (PCM) accumulation affected stresses and strains, values and spatial
distributions at the cellular subdomain and cell-matrix boundary. Constitutive
modeling also affected the absolute values though usually a similar trend was
observed.
