Tissue Engineering: Focus on the Musculoskeletal System - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 194

Collagen type I is an example of an extensively used polymer that is
derived from natural origins. As these materials are natural to the human
body, they are immediately recognized by cell surface receptors and can
have significant control over cell functions such as attachment, migration,
and proliferation. Collagen type I, in its raw form, can be used to fabricate
a broad range of scaffold structures, including hydrogel, sponge, film, or
as a composite. Decellularized tissues have also been explored as scaffolds
using tissues such as submucosa from the urinary bladder, small intestine,
or gallbladder. The advantage of these decellularized tissues is that they
have a predefined structure and contain biologically relevant growth factors.
However, since these naturally derived materials are often isolated from ani-
mal origins, their clinical uses are very limited owing to the potential threat
of immunogenicity and batch-to-batch variance.
A new paradigm in scaffold production has arisen recently that utilizes
matrix manufactured by the cells themselves in vitro. Choi et al. recently
described a cell-derived extracellular matrix composed of cartilage matrix
molecules secreted by porcine chondrocytes [7]. The chondrocytes were cul-
tured in monoculture for three weeks followed by a further three weeks in
a 3D pellet. The pellet was then freeze dried to remove any cell debris and
treated with DNase for purification. The final construct was a sponge-like
cartilage material composed mainly of collagen type II and sulfated glycos-
aminoglycan. Rabbit MSCs were seeded on these scaffolds, and the ability to
support chondrogenesis was evaluated both in vitro and in vivo in a mouse
model. The chondrocyte-derived ECM was highly efficient at forming carti-
lage in vitro when seeded with MSCs and delayed cartilage degeneration in
vivo. One limitation of this approach for clinical translation is the minimum
six-week waiting period required for scaffold manufacture. Lareu et al.
propose a strategy to overcome this problem by increasing the production
rate of ECM proteins in vitro [8]. Dextran sulfate and neutral dextran were
used as macromolecular agents, which resulted in a significantly improved
conversion rate of procollagen to collagen, a key component of the carti-
lage extracellular matrix. This kind of procedure may be used to produce a
patient specific cartilage surface in vitro, which could later be transplanted
to the patient in place of the degenerated surface.
Protein engineering has also been utilized to make tissue-engineering
scaffolds, which allows greater specificity over scaffold composition [9].
Modular peptide domains with various functionalities can be encoded into
a plasmid DNA, which is then transfected into an organism of choice to
produce proteins with molecular-level sequence specification. The materi-
als can be manufactured to contain functional modules that enhance cell
signaling, adhesion, and biodegradability; likewise they can also incorpo-
rate domains not normally found in natural ECM, such as DNA-binding
sequences [10]. However, one major drawback of many protein-engineered
scaffolds is the relatively weak mechanical properties, which limit their
uses for musculoskeletal-tissue engineering. In an attempt to overcome