Biomedical Engineering Reference
In-Depth Information
which resulted in correction of VUR without any evidence of obstruction. This bio-engi-
neered chondrocyte technology has been evaluated in two series of multicenter clinical trials:
the first trial included 29 patients (46 ureters) with grade II to IV VUR in which overall
reflux was corrected in 83% of cases [90]; and the second trial included patients with urinary
incontinence who were treated endoscopically with injected chondrocytes in which an
approximate success rate of 80% was observed at 3 and 12 months postoperatively [91].
Many childhood male cancer survivors suffer from sterility due to the long-term adverse
effects of chemotherapy and radiotherapy. Ideally, obtaining a small testicular biopsy prior
to anticancer therapy, freezing the tissue,
in vitro
propagation of spermatogonial stem cells
(SSCs) from stored tissue, and SSC autotransplantation can restore the fertility in sterile
male cancer survivors [92]. This process has been successfully performed in different species,
including non-human primates [93]. Recently, an
in vitro
propagation system for human
SSCs has been developed [17, 94] that represents an important step forward for translating
human SSC autotransplantation to the clinical setting in the near future.
Tissue Therapies
A commonly used strategy in the tissue-engineering field involves growing organs in the lab-
oratory. Stem cells or differentiated cells are seeded onto a biomaterial scaffold and allowed
to culture
in vitro
in a bioreactor for a short time, and then the bioengineered organ will be
ready to implant
in vivo
. These constructs are designed to replace a defective organ in its
entirety. Hollow organs, such as the urinary bladder, urethra, and blood vessels, have been
successfully engineered in the laboratory [95]. For example, several animal model studies
have shown that regeneration of urethral tissue is possible using various biomaterials
without cells, such as PGA and acellular-collagen-based matrices from the small intestine
and bladder [73, 96-98].
Acellular collagen matrices derived from bladder submucosa have been used. Experi-
mentally, segments of the urethra were resected and replaced with acellular matrix grafts.
Histological examination showed complete epithelialization and progressive vasculariza-
tion and muscle infiltration, which resulted in the ability of the animals to void through the
neo-urethras [73]. Subsequently, a clinical study of patients with hypospadias and urethral
stricture disease was carried out [99]. In that study, decellularized cadaveric bladder submu-
cosa was used as an onlay matrix. These patients were followed up to 7 years, and patent,
functional neo-urethras were noted. The use of any available matrix was determined to
be beneficial for patients with abnormal urethral conditions and obviates the need for
obtaining autologous grafts, thus decreasing waiting time for operation and eliminating
donor site morbidity.
These techniques are not applicable for tubularized urethral repairs because the collagen
matrices can replace urethral segments only when used in an onlay fashion. For patients
requiring a tubularized repair, the collagen matrices should be seeded with autologous cells
to avoid the risk of stricture formation and poor tissue development [100]. In addition, for
replacement of urethral segments that are longer than 1 cm, cell-seeded matrices must be
used [101]. Recently, the feasibility of using tissue-engineered urethras created from autolo-
gous cells was demonstrated in a preliminary study of five boys who had urethral defects
[102]. A tissue biopsy was taken from each patient, and the muscle and epithelial cells derived
from the biopsy sample were expanded and seeded onto tubularized PGA scaffolds to create
neo-urethras for implantation. After urethral reconstruction, these patients were followed
for up to 6 years. Urinary flow rates were increased in all of the patients. Serial radiographic
and endoscopic studies confirmed the maintenance of wide urethral calibers throughout the
follow-up period, and strictures did not develop. At 3 months post-surgery, urethral biopsies
