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Tissue Engineering in Urological and Gynaecological Applications

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Tissue Engineering in Urological and Gynaecological Applications

Urologisten ja gynekologisten sovellusten kudosteknologiaa

The tissue engineering applications has emerged as a new potential treatment method for urological and gynaecological applications. Hypospadia is the most common congenital malformation of penis, where the urethra opens ventrally to the shaft of penis or even perineum. The hypospadias are traditionally reconstructed using patients’ own genital tissue, or in severe cases non-urological graft tissue is used. However, the operations are susceptible to complications, especially in severe cases and when non-urological tissue is used. The most common complications are strictures, fistula formation and poor cosmetic outcome. Therefore, the development of alternative treatment methods is essential. Thus far, different natural and synthetic biomaterials, such as different acellular collagen based membranes, polylactide (PLA) and polyglycolide (PGA) have been studied as a growth surface for urothelial cells. However, the optimal biomaterial for urothelial applications has not been found yet. The biomaterial should be biodegradable, biocompatible, elastic, easy to handle and suture, support the urothelial cell growth and the structure of the de novo urethra. Further, the biomaterial should not evoke inflammatory tissue reaction.

Nowadays, the first-line surgical treatment for urinary incontinence is the mid-urethral sling operation, though, the development of injectable bulking agents is also important in order to obtain less invasive treatments. Previously, collagen and polyacrylamide hydrogel have been used as a bulking agent to treat stress urinary incontinence. Nevertheless, the sustainability of the treatment effect has been a major problem and additional injections have been required. Therefore, tissue engineering based injection therapies using stem cells, aiming regeneration of the damaged tissue, could solve the sustainability problem. Adipose stem cells (ASCs) isolated from adipose tissue are an attractive cell source due to their abundance. Further, ASCs are known to differentiate towards myogenic cell lineages, and therefore being potential to regenerate the muscle tissue and treat urinary incontinence.

This thesis is composed of two different parts. First, we studied the use of human amniotic membrane (hAM) and different synthetic biomaterial membranes, smooth (s) poly-(L-lactide-ε-co-caprolactone) (PLCL), textured (t) PLCL and knitted PLA mesh with compression moulded PLCL (cPLCL) as a growth surface for urothelial cells in vitro. In the second part, we evaluated the suitability of ASCs in combination with collagen gel to treat urinary incontinence in a clinical pilot study.

In the first part, the hAM did not support the hUCs proliferation, viability and phenotype compared to the PLCL. However, on all the studied synthetic biomaterials the hUCs maintained their viability and phenotype. Further, the cPLCL supported the hUCs proliferation slightly poorer compared to the sPLCL and tPLCL. In our clinical pilot study we demonstrated that ASCs in combination with collagen gel is a safe and moderately effective treatment method for female urinary incontinence. Further, ASCs derived from the treated patients were confirmed to differentiate towards myogenic, adipogenic, osteogenic and chondrogenic cell lineages in vitro. In conclusion, PLCL membrane could be a potential biomaterial for urothelial tissue engineering.

However, further research is needed to evaluate the in vivo applicability and biocompatibility of PLCL. Finally, tissue engineering based injection treatments with ASCs could be potential to treat female urinary incontinence in the future.

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