| dc.description.abstract | Over 400 million patients suffer from urinary bladder-associated physiological disorders
globally, which often necessitate surgical intervention for a reconstructive procedure. The
current gold standard for bladder reconstruction, an autologous graft, is proven not to be an
ideal substitute in clinics. Such unmet clinical needs drive the continuous surge for structural
and functional substitutes of urinary tissues, including ureters, bladder-wall, and urethra.
Against this backdrop, the present dissertation explores a biomaterial-based, functionalised
alloplastic platform for urological reconstruction. This strategy for an alloplastic urinary tissue
encompasses a biostable, 'off-the-shelf' available therapeutic option that simplifies and shortens
surgical treatment. Furthermore, it presents the potential to evade the challenges and
complications of autografts and scaffold-based regenerative techniques.
Considering the prerequisites of a urological alloplast, the combination of
polydimethylsiloxane and thermoplastic polyurethanes (TPU/PDMS) is deemed most
advantageous. The synergistic integration of varying contents of PDMS within the molten TPU
matrix is realised through a processing methodology of dynamic vulcanisation (DV). The
experimental outcomes are evaluated and correlated with different phenomenological models
to understand DV induced strengthening of structure. The theoretical predictions, in
conjunction with material property characterisation, allow a better understanding of the
improved interfacial behaviour and superior performance of the crosslinked polymer system.
The in situ compatibilised blends are further investigated for clinically relevant viscoelastic
properties to sustain high pressure, large distensions, and surgical handling/manipulation.
Moreover, non-exhaustive chemical strategies are harnessed to counter urinary tract infections
through the covalent incorporation of polycationic moieties. The new generation alloplasts,
endowed with contact killing surfaces, are assessed for their efficacy in pathogenically infected
artificial urine. In addition, the adhesion and proliferation of murine fibroblasts on different
polymeric compositions to establish their cytocompatibility.
Building further upon the knowledge of the antibacterial and antifouling activity of
polycationic modifications, layer-by-layer (LbL) assembled multifunctional surface grafting
are conceived to sustain long-term stability in a urinary environment, to suppress encrustation
and biofilm formation. The performance of the single-step and LbL-grafted blends is
benchmarked against the conventional urological alloplasts, using a customised lab-scale
bioreactor set-up. Post-six weeks of incubation in the dynamic assembly simulating ureasepositive microbial infection, the contact-active blends exhibited a remarkable ability to resist
calcium and magnesium encrustation, while retaining adequate grafting integrity. As high as
4-fold log reduction in the planktonic growth of bacterial strains associated with bladder stones
and renal calculi is recorded. In vitro cellular assessment is carried out with human
keratinocytes and human embryonic kidney cells to evaluate the cytocompatibility of the
surface grafted blends against the medical-grade control polymer. Finally, the optimum LbL
grafted formulations are investigated for their performance in a phase-I pre-clinical study
utilising human urine samples collected from 129 patients. The newly developed blends meet
the clinically desirable attributes and present a strong potential as a stable, contact-active, antiencrustation biomaterial platform for urinary implantation.
Summarising, this dissertation contemplates the new-generation, infection and encrustationresistant alloplasts. In pursuit of this vision, multifunctional polymeric biomaterials are
designed to sustain desirable performance in a urinary environment. These next-gen
biomaterials pave the way for an alloplastic platform that can integrate into clinical practice to
improve the quality of modern urological treatment. | en_US |
