Contact-Active Layer-by-Layer Grafted TPU/PDMS Blends as an Antiencrustation and Antibacterial Platform for Next-Generation Urological Biomaterials: Validation in Artificial and Human Urine

Abstract

Urinary tract infections and urinary encrustation impede the long-term clinical performance of urological implants and medical devices. Together, biofilm formation and encrustation constitute serious complications, driving the development of next-generation urological biomaterials. The currently available bioengineered solutions have limited success during long-term usage in the urinary environment. In addressing this unmet clinical challenge, contact-active, antiencrustation surface grafting were conceived onto a dynamically cross-linked polydimethylsiloxane (PDMS) modified thermoplastic polyurethane (TPU) blend using the layer-by-layer (LbL) assembly route. To the best of the authors’ knowledge, the present study is the first to investigate the LbL grafting in developing an antiencrustation platform. These multilayered assemblies strategically employed covalent cross-linking and electrostatic interaction-assisted progressive depositions of branched polyethyleneimine and poly­(2-ethyl-2-oxazoline). While polyethyleneimine conferred the contact-killing bactericidal activity, the much-coveted antiencrustation properties were rendered by incorporating a partially hydrolyzed derivative of poly­(2-ethyl-2-oxazoline). The performance of the resultant surface-modified TPU/PDMS blends was benchmarked against the conventional urological alloplasts, in a customized lab-scale bioreactor-based dynamic encrustation study and in human urine. After 6 weeks of exposure to an artificial urine medium, simulating urease-positive bacterial infection, the surface-modified blends exhibited a remarkable ability to suppress Ca and Mg encrustation. In addition, these blends also displayed superior grafting stability and antibacterial efficacy against common uropathogens. As high as 4-fold log reduction in the planktonic growth of Gram-negative P. mirabilis and Gram-positive MRSA was recorded with the LbL platform vis-à-vis medical-grade TPU. In conjunction, the in vitro cellular assessment with human keratinocytes (HaCaT) and human embryonic kidney cells (HEK) established the uncompromised cytocompatibility of the multilayered grafted blends. Finally, the physiologically relevant functionality of the LbL grafting has been validated using clinical samples of human urine collected from 129 patients with a broad spectrum of disease conditions. The phase-I pre-clinical study, entailing 6 week-long incubation in human urine, demonstrated significantly improved encrustation resistance of the blends. The collective findings of the present work clearly establish the success of LbL strategies in the development of stable, multifunctional new-generation urological biomaterials.

Tissue engineering in reconstructive urology—The current status and critical insights to set future directions-critical review

“…To achieve this, it is important to innervate the tissueengineered bladder. The process consists of the following steps: axonal outgrowth, neural survival, branching, and target nerve reconnection (Sharma and Bikramjit, 2022). Bladder reinnervation is a complex process, therefore many studies are in the initial stages of research.…”

“…Khang et al (2017) report a procedure that allows for engineering biphasic Janus-type polymeric nanofiber networks via the centrifugal jet spinning technique that provides unique structural support and biological activity and has many applications in tissue engineering approaches, such as where there might be a need for different properties on either side of the scaffold, such as environment resistance on one side and biocompatibility or potential therapeutic properties on the other side. Sharma et al (2022) used Contact-Active Layer-by-Layer Grafted TPU/PDMS and were able to validate TPU/PDMS blends as an antiencrustation and antibacterial platform for next-generation urological biomaterials with physiological relevancy for functionality. These layer-by-layer grafted blends displayed significant grafting stability and antibacterial efficacy against common uropathogens.…”

“… Sharma et al (2022) used Contact-Active Layer-by-Layer Grafted TPU/PDMS and were able to validate TPU/PDMS blends as an antiencrustation and antibacterial platform for next-generation urological biomaterials with physiological relevancy for functionality. These layer-by-layer grafted blends displayed significant grafting stability and antibacterial efficacy against common uropathogens.…”

“…Furthermore, Sivaraman et al provide evidence that Poly (Carbonate-Urethane)-Urea scaffolds possess high porosity and cytocompatibility, indicating their ability to support bladder cell growth and the formation of viable tissue. The researchers also demonstrated that the Poly (Carbonate-Urethane)-Urea scaffolds are suitable for the bladder’s primary functions of maintaining low pressure during storage and withstanding high pressure during voiding ( Sharma et al, 2021 ).…”

Surface modifications of biomaterials in different applied fields

“… 19 Sharma et al developed a stable, multifunctional, new-generation implantable urological biomaterial grafted with polyethyleneimine and poly(2-ethyl-2-oxazoline), which showed excellent antifouling performance and biocompatibility. 20 As a coating agent, SAMs have antifouling properties on the surface of biomaterials and resist the adsorption of non-specific proteins. 21 Among the surface modifications, hydrophobic surface is easy to cause protein adsorption, leading to biofilm formation.…”