Biomedical Engineering Reference
In-Depth Information
to augment the already promising silk fibroin matrix as an option for ligament
tissue engineering.
Engineered tendons, similar to ligaments, can display significantly enhanced
mechanical and morphological properties when subjected to mechanical loading.
The cyclic loading of tendon cells or mesenchymal stem cells, tenocyte
progenitors, can cause the cells to align with the strain axis on a construct and
result in higher construct stiffness. Tensile strain has been studied on a variety of
materials, ranging from collagen gels to decellularized biological scaffolds, such
as small intestine submucosa (SIS) and human umbilical vein (HUV) constructs,
as well as silk and synthetic materials [138, 139, 140, 141,142]. However, it is
clear that multiple variables relating to the mechanical stimulation, frequency,
strain amplitude, duration, and daily cycle number, can all influence the
characteristics of the final construct [143,144]. Functionalization of a scaffold
material has been shown to be possible by Kardestuncer
et al.
by tethering the
popular RGD motif to silk in order to augment the tendon-bone interface to
promote both adhesion of tenocytes and mineralization [145]. It is possible that
future endeavors with tendon tissue engineering will involve both mechanical
stimulation and also hybrid scaffolding materials to promote mechanical integrity
and cell adhesion, proliferation, and matrix synthesis.
3.5.
Hepatic tissue
Dynamic cell culture is especially relevant to hepatocyte culture, as they are a
cell type characterized by high metabolism and so need a constant nutrient and
oxygen source to maintain viability and phenotype stability [146, 147]. Tsang
et al.
explored the use of fluid perfusion through a photopatterned hydrogel with
encapsulated hepatocytes [148]. The adhesive RGDS peptide was incorportated
into a PEG hydrogel after the screening of multiple adhesive peptides.
Hepatocytes, RGDS, and the PEGDA crosslinking oligomer were
photopatterened in a triple layered construct which allowed media perfusion
through its fluidic channels. When placed in a previously designed perfusion
circuit at a flow rate of 0.5 mL/min, viable cells were visible through all three
layers at days 1 and 3 [149]. Longer cultures were allowed, up to 12 days, to
investigate albumin and urea synthesis, markers of metabolic function in the
liver. The dynamically cultured constructs produced higher levels of albumin and
urea than flat, unpatterned constructs with the same cell density. In addition, the
hydrogels containing 20 µmol/mL RGDS demonstrated 5 fold higher urea and
albumin levels than PEG-only controls in a 3 day, static study. This suggests
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