Engineering Fibrous Tissues and Their Interfaces with Bone - Structural Interfaces and Attachments in Biology - page 331

15.6 Conclusions
When rupture of tendon or ligaments occurs, graft surgeries can be performed to
restore function. However, these grafts are often not able to recreate original
mechanical properties, such as ultimate strength and elongation [ 4 ]. For this reason,
tissue engineering approaches have been investigated that possess the potential
to overcome the shortcomings of surgical procedures by fully restoring the
native tissue architecture and composition, including the fibrous tissue to bone
interface.
Fibrous tissue engineering utilizes cells, scaffolds, and/or exogenous factors in
various combinations. Cell types most commonly investigated include autologous
fibroblasts, dermal fibroblasts, and MSCs because they have demonstrated secretion
of tendon-/ligament-specific matrix molecules under the proper culture conditions
[ 74 ]. Both natural and synthetic scaffolds can act as cell carriers at a site of injury,
but must be optimized to facilitate cell attachment, differentiation, and upregulation
and secretion of ECM components while providing sufficient mechanical stability
at the defect site. Lastly, exogenous factors, such as growth factors and bioreactor
systems, have been explored to enhance cell culture environments and promote
tissue regeneration both in vivo and ex vivo .
While the means to regenerate fibrous tissues has been extensively studied,
engineering of the fibrous tissue interface to bone has not been explored in the
same depth. Interface tissue engineering has significant implications because cur-
rent graft surgeries do not restore interface structure or function [ 63 , 64 ]. Similar to
engineering fibrous tissues, interface engineering combines cells, scaffolds, and
exogenous factors, although more complex construct designs may be required than
for regular fibrous tissue engineering.
Many challenges remain before the ultimate goal of recreating tendon/ligaments
and their interfaces can be achieved. In addition to identifying a cell source with
appropriate expansion capabilities and a scaffold with proper degradation and
biological activity, it is difficult to fully implement a protocol for introducing
exogenous factors such as growth factors or mechanical stimulation when under-
standing of the signaling pathways by which these stimuli act has not been fully
elucidated. While results of proof-of-concept experiments are promising, tendon-/
ligament-bone interface tissue engineering provides an additional set of design
constraints in order to create regions that vary in mechanical properties and
composition. Therefore, the current combination of cells and scaffolds must be
optimized in vitro and further in vivo studies must be performed to confirm the
efficacy of these methods in restoring the transitional region.
While these challenges may appear daunting, recent advances in scaffold synthe-
sis and fabrication, basic biological understanding of both tendon and ligament
development as well as signaling pathways underlying mechanotransduction, and
identification of new potential cell sources hold promise to address the limitations of
current tissue-engineered constructs. Therefore, continued interdisciplinary research
to create the next generation of approaches that harness new findings from such