Biomedical Engineering Reference
In-Depth Information
greatly to impede scaffold degradation by collagenase and improve ultimate
tensile strength (UTS) of acellular collagen sponges.
54
Co-culture of human
fibroblasts and keratinocytes on these substrates reveals an apparent cytotoxicty of
the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) at high
concentrations (>10 mM EDC) with reduced cell viability and poor cellular
organization in CSS fabricated with cross-linked scaffolds. However, intermediate
concentrations of EDC can increase collagen sponge stability and strength while
providing an environment in which fibroblasts and keratinocytes can attach,
proliferate and organize in a manner conducive to dermal and epidermal regenera-
tion. In addition, EDC cross-linked collagen-GAG sponges are cleared from a
full-thickness wound in an athymic mouse within 12 weeks, leading to optimal
engraftment and stable wound closure.
92
These strategies can be used to produce
skin substitutes with increased and more predictable mechanical properties com-
pared to non-modified scaffolds.
12.7.2 Alternative biopolymer scaffolds
Scaffolds for tissue engineering play a critical role in regenerating functional
tissues and organs. The current model of skin substitutes utilizes a freeze-dried
collagen-GAG sponge populated with dermal fibroblasts and epidermal
keratinocytes. Freeze-drying is a labor intensive, costly process that can produce
sponges with significant structural heterogeneity
45,93
and is not easily scaled to
manufacturing levels. In addition, the collagen sponge is structurally different
from the natural extracellular matrix (ECM). Native ECM is fibrillar in structure
with micrometer to submicrometer sized fibers, while collagen sponges comprise
a reticulated network of collagen with pore walls that are several micrometers
thick. To overcome these limitations, alternative scaffold sources and fabrication
methods have been investigated.
Naturally derived matrices such as small intestine submucosa
26
and acellular
dermal matrices
25
have been utilized as scaffolds for skin tissue engineering.
Unfortunately, the inherent variation in natural materials coupled with the inability
to alter the structure of the material significantly detracts from their widespread
usage. Biopolymer gels have been successfully used both in a laboratory setting
94
and commercially.
21
While these gels have many advantageous properties, such as
biocompatibility, direct cellularity and being conducive to ECM deposition, they
are weak compared to the native tissue.
27
Electrospun matrices have also been
investigated as scaffolds for skin substitutes owing to their ease of manufacture
and the ability to select their physical, chemical and mechanical properties.
Electrospinning is an inexpensive, scalable process that has been used to
fabricate nonwoven fibrous scaffolds from a wide array of materials including
collagen.
95-100
In electrospinning, polymer solution is pumped through an aperture
(i.e. syringe needle) that is electrically charged. A charge is induced on the liquid
droplet at the tip of the needle by the electric potential between the needle and a
