Biomedical Engineering Reference
In-Depth Information
FIGURE 20.9
Tub e s p r o duc e d f r om p oly( la c t ic -
co
-glycolic acid) foams fabricated using thermally induced
phase separation techniques show poor mechanical stability when implanted
in vivo
, collapsing after 1 week
of subcutaneous implantation. Arrows indicate the collapsed lumen in a histological cross-section of the
implanted tube.
The problems associated with mechanical stability of the tubular scaffolds add to a list of obsta-
cles arising from these early tissue engineering studies that have yet to be resolved before intestinal
tissue engineering can be applied to humans, many of which can be attributed to the biomaterials
currently being used to fabricate the scaffolds.
Other concerns raised include the ability to engineer suffi cient lengths of intestine. Some of the
tissue-engineered constructs produced to date have measured only approximately 1 cm in length.
Even for a small animal model, such lengths of intestine are unlikely to produce a signifi cant increase
in the nutrient absorptive capacity of the intestine. Moreover, the production of a 1 cm length of
engineered intestine has required all of the intestinal epithelial cells harvested from approximately
one-and-a-half syngeneic donor intestines, a procedure that could not feasibly be translated to
humans. The ineffi cient use of cells with this approach probably results from poor attachment and
spreading of cells to the biomaterials used to fabricate the scaffolds. Future scaffolds might consist
of biomaterials that have had key protein components of the intestine incorporated into them, which
promote cell adhesion and spreading.
20.7.2.3 Collagen-Based Scaffolds
Naturally derived biomaterials, such as porcine small intestinal submucosa, have also been used for
intestinal tissue engineering scaffolds [79,85]. Small intestinal submucosa is an obvious choice for
intestinal tissue engineering since this biopolymer is derived from a tissue that in its native form
provides support for the growth and differentiation of mucosal tissue while also functioning as a
connective tissue structure that provides mechanical strength to the structure of the intestine [86].
Small intestinal submucosa biomaterials can be fabricated from freshly harvested porcine small
intestine by inverting the tubular tissue and mechanically delaminating the outer muscular lay-
ers (tunica muscularis externa) and internal mucosal (tunica mucosa) layers from the submucosal
tissue (tunica submucosa) [86]. The resulting submucosal tissue with basilar layers of the mucosa
consists of a membrane about 80-100 µm thick. The membrane is rinsed in water, treated with an
aqueous solution of 0.1% peracetic acid, and rinsed further in water and phosphate buffer saline
to remove any remaining cells and to provide the small intestinal submucosa with a neutral pH.
To increase the thickness of small intestinal submucosa, additional layers have been stacked on top
before compressing and drying. Small intestinal submucosa is sterilized with 2.5 mRad gamma
irradiation to produce a sterile, pyrogen-free biomaterial consisting of a complex mixture of
