3. Normal wound healing has been studied extensively and is
helpful in maximizing success for the engineering of tissues
At the time of tissue injury, cell ingrowth is initiated from the
wound edges to cover the tissue defect
Cells are able to traverse short distances without any
detrimental effects
wound is large, more than a few millimeters in distance or
depth, increased collagen deposition, fibrosis, and scar
formation ensue
4. Matrices implanted in wound beds are able to lengthen the
distances that cells can traverse
Tissue defects greater than 1 cm that are treated with a matrix
alone, without cells, usually have increased collagen deposition
Cell-seeded matrices implanted in wound beds are able to
further lengthen the distance for normal tissue formation without
initiating an adverse fibrotic response
5. Urethra
Naturally derived collagen-based materials such as
Woven meshes of PGA without cells and with cells
bladder-derived acellular submucosa
acellular urethral submucosa
collagen gels
bladder submucosa matrix proved to be a suitable graft for
repair of urethral defects
Nonseeded acellular matrices, were applied in a successful
manner for onlay urethral repairs
6. Urethra
Atala et al, 1999
Neourethras were created by anastomosing the matrix in an on-
lay fashion to the urethral plate
size of the created neourethra ranged from 5 to 15 cm
After a 3-year follow-up,
3 or 4 patients had a successful outcome with regard to
cosmetic appearance and function
One patient who had a 15-cm neourethra created developed a
sub-glanular fistula
7. Urethra
Acellular collagen-based matrix
Eliminated the necessity of additional surgical procedures for
graft harvesting,
Potential morbidity from the harvest procedure were
decreased
Reduced operative time
But when tubularized urethral repairs were attempted
experimentally, adequate urethral tissue regeneration was
not achieved and complications ensued(contracture &
Stricture).
8. Urethra
To overcome this bladder epithelial and smooth muscle cells
were grown and seeded onto preconfigured tubular matrices
Entire urethra segments were resected and
urethroplasties were performed with tubularized collagen
matrices seeded with cells
9. Urethra
Raya-Rivera et al, 2011
5 patients with urethral injuries
had a small tissue biopsy specimen retrieved
cells were expanded in vitro and seeded in two layers on
tubularized scaffolds that were implanted surgically
engineered urethras were able to show adequate anatomy,
both by urethroscopy and with urethrography and function
long term
10.
11. Bladder
Currently, gastrointestinal segments are commonly used as
tissues for bladder replacement or repair
GI tissues are designed to absorb specific solutes
whereas bladder tissue is designed for the excretion of solutes
Thus, multiple complications may ensue, such as infection,
metabolic disturbances, urolithiasis, perforation, increased
mucus production, and malignancy
12. Bladder
Matrices
Synthetic materials that have been tried include polyvinyl
sponge, Teflon, collagen matrices, Vicryl (PGA) matrices, and
silicone
Permanent synthetic materials used for bladder reconstruction
succumb to mechanical failure and urinary stone formation
use of degradable materials leads to fibroblast deposition,
scarring, graft contracture, and a reduced reservoir volume over
time
13. Bladder
Non-seeded allogeneic acellular bladder matrices have
served as scaffolds for the ingrowth of host bladder wall
components serve as vehicles for partial bladder regeneration
Acellular collagen matrices can be enhanced with growth
factors to improve bladder regeneration
Cell-seeded allogeneic acellular bladder matrices showed
better tissue regeneration
14. Bladder
SIS, a biodegradable, acellular, xenogeneic collagen-based
tissue matrix graft, was first described in early 1960s
derived from pig small intestine in which mucosa is
mechanically removed from inner surface and serosa and
muscular layer are removed from outer surface
Non seeded SIS matrix used for bladder augmentation is able
to regenerate in vivo
transitional layer was the same as that of the native bladder
tissue but muscle layer was not fully developed
15. Bladder
Regenerative medicine with selective cell transplantation in SIS
may provide a means to create functional new bladder
segments.
Native cells are currently preferable because they can be used
without rejection
Amniotic fluid– and bone marrow–derived stem cells have the
potential to differentiate into bladder tissue and urothelium.
Embryonic stem cells also have the potential to differentiate into
bladder tissue.
16. Bladder
A study using engineered bladder tissue for cystoplasty
reconstruction was conducted starting in 1998
pilot study of seven patients was reported , Atala et al, 2006
Patients underwent reconstruction with the engineered bladder
tissue created with the PGA-collagen cell-seeded scaffolds
with omental coverage
showed increased compliance, decreased end-filling pressures,
increased capacities, and longer dry periods over time
18. Bladder cell therapies
Injectable therapy within the bladder may be useful for SUI and
VUR
Injection of chondrocytes for the correction of VUR in children
At 1-year follow-up, reflux correction was maintained in 70%
SUI in adults have been attempted
After 1 year, 1/8 women achieved total continence and 5 reported
improvement
19. Bladder cell therapies
autologous smooth muscle cells was explored for urinary
incontinence, SUI and VUR applications
myoblasts isolated from the abdominal wall vasculature were
injected in a series of bladder exstrophy patients with urinary
incontinence.
88% of patients were socially dry
The patients were also on a pelvic floor electrical stimulation and
pelvic floor exercise program
20. Ureters
Collagen tubular sponges
Ureteral decellularized matrices
Cell-seeded biodegradable polymer scaffolds have
been used as cell transplantation vehicles to
reconstruct ureteral tissues
Urothelial and smooth muscle cells isolated from
bladders and expanded in vitro were seeded onto
PGA scaffolds with tubular configurations and
implanted subcutaneously resulted in the eventual
formation of natural urothelial tissues
21. Male Genital And Reproductive Tissue
One of the major limitations of genital reconstructive surgery is
the availability of sufficient autologous tissue
Phallic reconstruction was initially attempted in the late 1930s,
with rib cartilage but discouraged because of the unsatisfactory
functional and cosmetic results
Silicone rigid prostheses were popularized in the 1970s and
have been used widely but biocompatibility issues have been a
problem
22. Male Genital And Reproductive Tissue
Reconstruction of Penile Corpora
Cultured human corporeal smooth muscle cells may be used in
conjunction with biodegradable polymers to create corpus
cavernosum tissue de novo
Falke et al, 2003
Human corpus cavernosal muscle and ECs were derived from
donor penile tissue, and the cells were expanded in vitro and
seeded on the acellular matrices.
The matrices were covered with the appropriate cell architecture
4 weeks after implantation
23. Male Genital And Reproductive Tissue
Reconstruction of Penile Corpora
Experimental corporeal bodies
demonstrated intact structural integrity
by cavernosography and showed
similar pressure by cavernosometry
when compared with normal controls
Mating activity in the animals with the
engineered corpora appeared normal
by 1 month after implantation
Sperm was present in all and were able
to father healthy offspring.
24. Male Genital And Reproductive Tissue
Penile Cell Therapy
Various cell lines have been used in animal models in an
attempt to reverse erectile dysfunction in animal models
Endothelial cells
Mesenchymal stem cells either alone or with matrices
human bone marrow–derived stem cells
Muscle-derived stem cells
Long-term studies are needed to gauge the full impact of
these therapies
25. Penile transplant
Such a scaffold could represent a new solution in cases of total penile loss after
cancer or trauma or in transgender surgeries, cases where the incidence is
increasing rapidly.
26. Male Genital And Reproductive Tissue
Testis – Leydig cells
Patients with testicular dysfunction require androgen
replacement for somatic development in form of
periodic intramuscular injections
Skin patch applications
Long-term non-pulsatile testosterone therapy is not
optimal and can cause multiple problems
27. Male Genital And Reproductive Tissue
Testis – Leydig cells
Leydig cells were microencapsulated in an alginate-poly-L-
lysine solution for controlled testosterone replacement
Provides a barrier between the transplanted cells and
the host’s immune system, as well as allowing for the
long-term physiologic release of testosterone
On similar principles, testicular prostheses have been
created with chondrocytes and loaded with testosterone
28. Male Genital And Reproductive Tissue
Testis – Spermatogenesis
Spermatogenesis for infertility purposes has been a major area of
interest
First successful isolation of human spermatogonial stem cells in
2002 showed that the cells were able to colonize and survive for 6
months in mice recipient testes
Successful autologous and allogeneic spermatogonial stem cell
transplantation has been demonstrated
In vitro propagation of human spermatogonial stem cells from both
adult and pubertal testes has been established
29. Female Genital And Reproductive Tissue
Uterus
Congenital malformations of the uterus may have profound
implications clinically
possibility of engineering functional uterine tissue using
autologous cells was investigated
Autologous uterine smooth muscle and epithelial cells were
harvested, grown, and expanded in culture.
These cells were seeded onto preconfigured uterine-shaped
biodegradable polymer scaffolds, which were then used for
subtotal uterine tissue replacement
30. Female Genital And Reproductive Tissue
Vagina
Many techniques and materials can be used successfully for
vaginal reconstruction
most common, creating a canal by dissecting the potential
neovaginal space and subsequently lining the pelvic canal with a
graft
Vaginal epithelial and smooth muscle cells were harvested,
expanded, and seeded on biodegradable polymer scaffolds
31.
32. Female Genital And Reproductive Tissue
Ovary
Ovarian tissue is essential for fertility.
Recent studies have shown that ovarian cells can be derived
from stem cell populations. The cells can lead to the
production of oocytes and embryos
Cell therapies have also been used to enhance the
functionality of the ovary
Adipose-, amniotic fluid–, umbilical cord–, and bone
marrow–derived stem cells have all resulted in a return of
experimentally damaged ovarian function in animal models
33. Renal Structures
Isolation of particular cell types that produce specific factors
may be a good approach for selective cell therapies
Cells that produce erythropoietin have been isolated in culture,
and these cells could eventually be used to treat anemia that
results from ESRD
More ambitious approaches involve working toward the goal of
total renal function replacement
34. Renal Structures
Nuclear material from bovine dermal fibroblasts was transferred into
unfertilized enucleated eggs.
Renal cells from the cloned embryos were harvested, expanded in
vitro, and seeded onto three-dimensional renal devices.
The devices were implanted into the back into the steer and were
retrieved 12 weeks later.
This process produced functioning renal units
Cells derived from nuclear transfer can be successfully harvested,
expanded in culture, and transplanted in vivo with the use of
biodegradable scaffolds on which the single suspended cells can
organize into tissue
35.
36. Renal Structures
These studies were the first demonstration of the use of
therapeutic cloning for regeneration of tissues in vivo
Renal cells seeded on the matrix adhered to the inner surface
and proliferated to confluency by 7 days after seeding. Renal
tubular and glomerulus-like structures were observed 8 weeks
after implantation
More recent data has confirmed that the creation of larger
kidney structures using decellularized kidney matrices and
repopulated with cells is possible
