Biomedical Engineering Reference
In-Depth Information
extracellular matrix molecules including collagen type I, III, IV, V, VI; proteoglycans; glycopro-
teins; and glycosaminoglycans [79,87]. To make tubular scaffolds, the small intestinal submucosa
has been soaked in saline to make it pliable and soft and wrapped around an appropriately sized
glass tube before sewing the edges together with an absorbable suture [79].
The suitability of this type of material for intestinal tissue engineering remains uncertain. When
pieces of tubular small intestinal submucosa scaffold measuring 6 cm long and 2 cm in diameter
were anastomosed to the native intestine in a canine model, all recipients suffered signifi cant mor-
bidity. This was apparently caused by leakage from the site of anastomosis or stenosis caused by
the tube collapsing [79]. Also, despite the large number of studies having reported successful use
of small intestinal submucosa as an acellular xenograft material, concerns have been raised about
the clinical safety and effi cacy of small intestinal submucosa-derived biomaterials. Noninfectious
edema and severe pain has been observed at sites of implantation in some patients, a response sug-
gested to be caused by the possible retention of multiple layers of porcine cells and DNA material
causing an infl ammatory response [88].
20.7.2.4
Indirect Three-Dimensional Printed Scaffolds
Indirect three-dimensional printing is another approach that has been used to fabricate porous tissue
engineering scaffolds that can be modifi ed to include villi features, making them a suitable scaffold
for intestinal tissue engineering [89]. Three-dimensional printing creates three-dimensional scaf-
fold structures by ink-jet printing liquid solvent binder droplets to join loose particles of polymer.
After the solvent has dissolved the polymer, it evaporates allowing the polymer to reprecipitate
forming a solid structure. The remaining polymer particles are leached out to produce a porous
scaffold. Porogens can also be mixed with the polymer to further increase porosity. The printing
process is computer-aided, allowing parameters such as micro- and macrostructure, mechanical
properties, porosity, and composition to be optimized. Indirect three-dimensional printing has been
proposed as a way of overcoming limitations associated with direct printing, such as pore size,
shape complexity associated with the use of organic solvent liquid binders, and the need for custom-
ized machines when using biodegradable polymers and solvents. Indirect three-dimensional print-
ing involves printing a plaster mold and solvent-casting the polymer into the mold cavity. Molds to
fabricate scaffolds with small villi (850 µm diameter, 150 µm apart) were designed by computer
software. The water-based binder was printed onto layers of plaster powder (average particle size
∼
20 µm) to form a two-dimensional pattern. The process was repeated to form additional layers until
the desired three-dimensional mold was completed. The molds were dried and infi ltrated with poly-
ethylene glycol to block surface pores in the mold and to increase its mechanical strength. For the
solvent-casting process, sucrose particles (100-150 µm) were mixed into a solution of poly(lactic-
co
-glycolic acid) dissolved in chloroform and methanol and cast into the molds. After the scaffolds
were freeze-dried, the molds and sucrose were leached simultaneously by immersing in deionized
water. The outer surface of the scaffolds was further cleaned and modifi ed by etching with ethanol
and coated with fi bronectin to increase adhesion, viability, and proliferation of rat intestinal epithe-
lial cells seeded onto the surface. The epithelial cells were initially attached uniformly throughout
the scaffold, but after longer periods of culturing, the cell density increased in the villi-shaped
regions but remained low within the scaffold, possibly due to limited diffusion of oxygen and nutri-
ents [89]. The use of such techniques to fabricate a scaffold containing villi is advantageous as it
would increase the absorptive surface area of tissue-engineered intestinal construct.
20.7.2.5
Neovascularization of Intestinal Tissue Engineering Scaffolds
Suffi cient neovascularization of tissue is essential to provide oxygen and nutrient delivery and
removal of waste products to cells. Vascularization of tissue constructs is an important obstacle
that is yet to be overcome satisfactorily in the engineering of any tissue larger than a few millime-
ters in volume. As with the majority of other organs tissue engineered to date, this problem affects
