Engineering Fibrous Tissues and Their Interfaces with Bone - Structural Interfaces and Attachments in Biology - page 323

15.4.2 Scaffolds
Scaffolds may be used to deliver cells and provide a structural support at a site of
injury. Scaffolds must allow for cell attachment, contain pores for secretion of
appropriate ECM molecules, allow bioactive molecules to access the cells, inte-
grate into the injured tissue area, and have the ability to translate mechanical cues
from the environment to the engineered construct [ 90 ]. Integration into the tissue is
achieved by designing biodegradable materials that degrade at the same rate new
tissue is formed [ 27 ].
Poly(esters) are a common synthetic scaffold material for tendon and ligament
tissue engineering. This class of fibers can be manipulated to form woven matrices
that enhance mechanical strength [ 91 ]. Polymer degradation is achieved hydrolyti-
cally and the byproducts are metabolically removed or remain inert. The most
common poly(esters) include poly(lactic acid) (PLA), poly(glycolic acid) (PGA),
and poly(lactic-co-glycolic acid) (PLGA) [ 92 ]. A study using a twisted PLA
scaffold seeded with human MSCs resulted in upregulation of collagen type I,
tenascin-C, and decorin gene expression after 15 days in culture [ 93 ]. These results
suggest that a PLA scaffold allowed for homogenous cell seeding and fibroblastic
gene expression, making this material a promising scaffold candidate for ligament
tissue engineering. Another study using PGA as a scaffolding material reported the
ability to restore mechanical capacity of tendon gap defects in a hen flexor tendon
model [ 94 ]. After 14 weeks, histology revealed that the engineered PGA scaffold
with autologous tenocytes had undistinguishable structure to native tendon tissue
and biomechanical analysis demonstrated higher breaking strength of PGA
scaffolds comparable to normal tendon strength [ 94 ]. Lastly, knitted PLGA seeded
with bone marrow stromal cells implanted into an Achilles tendon gap defect in
rabbits demonstrated tissue regeneration and improved mechanical properties after
12 weeks [ 95 ]. Immunohistochemical assays revealed the formation of collagen
type I and collagen type III fibers in regenerated tissue and mechanical testing
characterized the scaffold construct as having a tensile modulus similar to that of a
normal tendon control [ 95 ]. Synthetic polymers are advantageous because the
composition of the material can be easily controlled [ 92 ]. These biomaterials are
easy to tailor for specific applications and are more readily available than natural
materials because they can be synthesized in a laboratory setting. However, because
synthetic materials are not found in native tissue, they have less ability to direct
tissue growth without further biological modification [ 96 ].
In contrast, naturally based scaffolds are advantageous over synthetic materials
because many are already found in the body, therefore it is believed that these
materials may incorporate and be remodeled more like native tissues [ 92 ]. In
addition, many already possess bioactive molecules that can interact with seeded
cells. However, unlike synthetics, one drawback of naturally based materials is that
it may be difficult to obtain large enough amounts of pure product for clinical scale-
up [ 96 ]. Since collagen composes the bulk of fibrous tissues for tendon and
ligament applications, natural scaffold materials often utilize collagen fibers in