In vivo tissue-engineered augmentation cystoplasty with electrospun scaffold made of poly(εcaprolactone) and poly(hydroxyalcanoate): mid-term results in a small animal model.
Vianello A., Zucchi A., Bianco A., Del Gaudio C., Bellezza G., Toraldo M., Sidoni A., Porena M.
Department of Medical-Surgical Specialties and Public Health, Urology Section, University of
Perugia, Italy.
Department of Experimental Medicine and Biochemical Sciences, Institute of Pathological
Histology and Anatomy, University of Perugia, Italy
Department of Chemical Sciences and Technologies, Univeristy of “Tor Vergata”, Rome, Italy.
Introduction and Objectives
Often bladder augmentation cystoplasty or radical cystectomy is necessary for functional diseases
or muscle-invasive bladder cancers. The intestine is still the gold standard, but affected by many
complications.
We have previously demonstrated promising results performing bladder augmentation cystoplasty
in rats with nude electrospun scaffold made of poly(ε-caprolactone) (PCL) blended with a naturallyderived polyester belonging to the family of poly(hydroxyalcanoate) (PHA). In the present study we
aimed at evaluating mid-term behavior of the electrospun scaffolds.
Methods
6 to 8 weeks old female Wistar rats (weight≈250 gr) underwent an augmentation cystoplasty with a
5 mm diameter electrospun scaffold made of PCL intimately blended with an equal weight amount
of PHA. The scaffolds were comprised of uniform and homogeneous dense fibers that delimited a
3D network of interconnected voids. The average fiber size was 3.0±0.1 µm and the average 2D
void size was 8±3 µm. The scaffold was anastomosed to the native bladder with two running
readsorbable 8/0 sutures under microscopic white light view.
3 and 6 months after surgery the animals were euthanized with CO2 and cervical dislocation, the
bladder taken out, fixed in 4% paraformaldehyde and included in paraffin. Hematoxylin & eosin
and imunohistochemistry with antibodies against desmin and pancytocheratin (AE1/AE3) were
performed on 4 μm thick slices including the scaffold and the native bladder. An equal number of
healthy rats were used as controls.
Results
8 rats underwent surgery. 5 rats were euthanized at 3 and 3 at 6 months, respectively. All around the
bladders it was still visible an intense foreign body reaction with no dehiscence of the anastomosis.
Fig. 1: with time the inflammation tended to disappear gradually (asterisks), a gradual reconstitution
of the entire bladder wall on the top of the scaffold to build a “new dome” was present with the
scaffold dislocated into the bladder lumen at 3 months (triangle), the bladder wall was reconstituted
with the growth of both normal urothelium (arrowheads) and fibrils of smooth muscle cells
(arrows). 6 months after surgery the scaffold disappeared, probably partially reabsorbed and
partially discharged with urine. Fig. 2 shows imunohistochemistry.
Conclusions
These surprising mid-term results of bladder augmentation cystoplasty in rats performed with
electrospun scaffold allow us hypothesize PCL intimately blended with PHA are a viable option for
urinary diversions in humans. Needful long-tern morphological and functional evaluations are
ongoing in our lab.