Tissue engineering applications in urology include organ transplantation, reconstructive procedures, and novel therapies for chronic illness. Studies have reconstructed tissues of the urethra, bladder, and male genitalia using cell-seeded matrices. For the urethra, tubular matrices seeded with autologous cells generated neourethral segments of 5-15cm. For the bladder, acellular matrices and cell-seeded matrices showed regeneration of transitional layers. Reconstructing penile corpora used smooth muscle cells on biodegradable scaffolds, generating intact structures. Tissue engineering offers alternatives to gastrointestinal tissues currently used for reconstruction and potential treatments for conditions like erectile dysfunction and infertility.

1. Tissue engineering
Applications in Urology
Dr. Roshan V Shetty
Senior Resident In Urology
AJIMS &RC

2.  Organ transplantation
 Tissue for reconstructive procedures
 Novel therapies for chronic illness

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

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

17. Bladder

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

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

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

37. Thank You