Assignment
Assignment
Assignment
Collagen is a naturally occurring matrix polymer which is highly conserved across species. It
is the predominant extra-cellular matrix component of most connective tissues within the
mammalian body, comprising one third of all protein found within tissues. Collagens are
extracellular and have a mainly structural role. Critical parameters including density, packing
and orientation (or direction) results in distinctively varying mechanical properties in tissues
such as bone, skin, tendon and cartilage.
In connective tissue lost to trauma or disease, replacement tissue strategies, have to consider
mechanical implications. Synthetic polymers can be designed to have the mechanical integrity
of the native structure to be replaced but eventually this will be degraded and replaced by the
host. The major target protein that will be replaced in connective tissues is collagen. The other
alternative is to start with collagen as a natural polymer substrate and tailor its mechanical
properties in vitro. Given the critical role this protein plays in tissue structure there have been
and continue to be efforts into extracting this protein, reforming 3D scaffolds for tissue
engineering as well as controlling density and direction parameters to form tissues in vitro. The
main difference in the building of bulk tissues is the cell-rich or matrix-rich nature of the tissue
being engineered. Where the matrix dominates a tissue, the mechanical properties of the matrix
are critical, i.e in connective tissue. In tendon for example, the alignment of collagen fibrils
along the principle axis of strain application, and the nature of a ‘dual’ size of fibril diameters,
provides incredible strength to this tissue. Compared directly to a tissue like dermis, where
collagen is interlocked in a basket-weave formation with elastin to provide tensile strength in
multiple axis to ensure stretching of this tissue does not compromise its integrity. Thus, when
engineering tissues in vitro, technologies and processing to control parameters of collagen
architecture have been developed to mimic those found in tissues in situ. This field of controlled
processing is growing, as the sophistication of methods employed to create biomimetic
scaffolds advances.
Type I collagen scaffolds are widely used in clinical practice and the collagen for these
materials are generally obtained either from cultured cells or extracted from native tissues.
Extraction encompasses the entire range from decellularisation of collageneous tissues
preserving the native architecture to the complete break down into collagen molecules which
can later be reconstituted into their native fibrillar structure. One of the most common collagen
scaffolds in clinical use is de-cellularised dermal tissue. By decellularising an entire piece of
connective tissue, the immunogenicity of the tissue is removed whilst retaining the collagen
architecture and other matrix components in the native form. These scaffolds induce and guide
tissue repair when implanted in a full-thickness skin defect as a template for dermal
regeneration. Methods to enhance the in vivo persistence of such decellurarised scaffolds,
involve dispersion of the collagen matrix. The dispersion of collagen can result in the
degradation of the collagen into polymers, oligomers or monomers dependent upon the
treatment methods applied. This is followed by co-precipition with a glycosaminoglycan. In
these cases the inherent architecture of the native tissue is lost and reformed in vitro.
The formation of living collagenous tissue equivalents rely upon the cell seeding of
decellularised native tissues or cell-seeding into prefabricated, porous collagen scaffolds. The
next generation of skin equivalents are bio-engineered cell based technologies using cell
produced collagen. These include the next generation bilayered skin equivalents produced by
Organogenesis. The use of solubilised collagen as dermal and lip fillers for the correction of
contour deformaties, is a growing cosmetic procedure. This relies upon collagen dispersion
from either human cadaver or bovine tissue, which can then be stably re-injected to ‘plump’ to
fill minor defects. The question is whether the fibrosis response by the injection of these
products causes the therapeutic effect or the products themselves.
The main focus of this chapter is to address the importance of collagen protein structure and
its relation to normal mechanical function in matrix-rich tissues. This chapter will overview
the established, clinically used and new novel processing technologies being researched to
improve and control bulk collagen processing for applications in regenerative medicine, and
new directions needed to control collagen architecture.