Tissue Engineering: Focus on the Musculoskeletal System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 195

this problem, muscle-mimicking protein has been engineered based on the
molecular structure of titin [11], a complex molecular spring located within
the I-band of muscle tissue and largely responsible for the muscle's elas-
ticity. The polyprotein comprises a composite of GB1 and resilin, both of
which were produced by overexpressing DH5α cells containing pQE80L
vectors modified with genes representing both proteins. The collected pro-
teins were combined and photochemically crosslinked to produce biomate-
rial constructs. The resulting constructs were rubber-like and showed high
resilience to low strain while acting as a shock-absorber under high strains,
hence the material can effectively dissipate energy at high strain levels,
much like that of muscle tissue. All the results from this study were based
on the evaluation of mechanical properties; however, it would be interesting
to quantify cell response, for example, whether stem cells can recognize this
as a muscle-like ECM and differentiate down the myogenic lineage, or how
cells attach and migrate along the synthesized surface. This research is an
excellent example of how molecular engineering can be utilized to fabricate
tissue-like materials.
Engineering Functional Materials
Engineering functionality into a synthetic material would better mimic nat-
ural extracellular environment and promote desired cell fate and tissue func-
tions. Extensive research effort has been dedicated to design the architecture
of scaffolds to influence the cellular fate processes. When plated on electro-
spun grooved materials, cells will align in the direction of the grooves, and
such a technique has been used to direct neuronal cell alignment for spinal
cord regeneration. Specific pore sizes have also been engineered to attract
certain cell populations, and this technique was explored to attract chondro-
cytes to the cartilage side of an osteochondral implant [12]. In a recent study,
Engelmayr et al. have developed “accordion-like honeycombs” that contract
with beating cardiac cells for cardiac tissue engineering (Figure 9.1) [13]. The
scaffolds are fabricated using excimer laser microablation to induce an accor-
dion-like architecture in poly(glycerol sebacate) (PGS). The resulting scaf-
folds were seeded with neonatal rat myocytes, which pulsed the scaffold in
a preferred direction according to the design of the honeycomb repeat units.
Bi-layered scaffolds were also formed in this study by stacking scaffolds at
an oblique angle, which enables interporous connectivity and cell infiltra-
tion throughout the network. As with all scaffold for tissue engineering, this
design also faces a number of limitations [14]. The overall thickness of the
scaffold may hinder oxygen diffusion throughout, hence preventing healing
at the injury site. Various techniques have been designed to support vascu-
larization and oxygen diffusion throughout scaffolds, as discussed in the
signals section below. This study demonstrates how architecture can be used
to functionalize a tissue-engineering scaffold, and more in-vivo work would
be important to further validate its efficacy for cardiac tissue engineering.