Interactive Effects of Copper-Doped Urological Implants with Tissue in the Urinary Tract for the Inhibition of Cell Adhesion and Encrustation in the Animal Model Rat

At a Glance

Metadata	Details
Publication Date	2022-08-16
Journal	Polymers
Authors	Wolfgang Kram, Henrike Rebl, Julia E. de la Cruz, Antonia Haag, Jürgen Renner
Institutions	University of Freiburg, University of Rostock
Citations	7
Analysis	Full AI Review Included

Technical Documentation and Analysis: Copper-Doped Diamond-Like Carbon Coatings for Biomedical Implants

This document analyzes the research concerning copper-doped amorphous hydrogenated carbon (a-C:H/Cu-multilayer) coatings for urological implants, focusing on biocompatibility, antibacterial efficacy, and encrustation behavior. It highlights how 6CCVD’s advanced MPCVD diamond materials and customization capabilities can overcome the key limitations identified in the study, driving future research and commercial applications.

Executive Summary

The following points summarize the core findings and the value proposition for utilizing advanced diamond materials in this application:

Antibacterial Efficacy: A therapeutic window of 0.5 mM to 1.0 mM CuCl₂ was successfully identified, demonstrating the ability to eliminate Escherichia coli viability (to < 1%) while maintaining excellent human urothelial cell viability.
Biocompatibility Confirmed: The Elastollan base material and the a-C:H/Cu-multilayer coating showed very good biocompatibility in vitro, and copper release in vivo remained below the non-toxic threshold (< 250 µg/g dry weight) in rat tissue and blood serum.
Hybrid Deposition: The coating was achieved using a hybrid PVD-PECVD process, alternating 200 nm layers of a-C:H (DLC) and nanoscale copper multilayers.
Critical Limitation Identified: The study concluded that the increased surface roughness of the a-C:H/Cu-multilayer coating was the causal factor for significantly higher encrustation rates in the rat model.
6CCVD Value Proposition: 6CCVD specializes in ultra-smooth MPCVD diamond (SCD/PCD) substrates (Ra < 1nm). Utilizing these materials as the foundation for DLC/Cu deposition directly addresses the roughness-induced encrustation problem, enabling the full antibacterial potential of the coating.

Technical Specifications

The following hard data points were extracted from the process parameters and experimental results:

Parameter	Value	Unit	Context
SCD/DLC Layer Thickness (Process 1)	200	nm	PECVD a-C:H layer in multilayer stack
Copper Layer Thickness (Process 2)	200	nm	PVD magnetron sputtered Cu layer in multilayer stack
PECVD RF Excitation Power	250	W	a-C:H deposition parameter
PVD RF Excitation Power	150	W	Cu deposition parameter
PECVD Bias Voltage	230	V	a-C:H deposition parameter
PVD Bias Voltage	130	V	Cu deposition parameter
Therapeutic Copper Concentration Range	0.5 - 1.0	mM	Kills E. coli without significant urothelial cell impairment
Urothelial Cell Viability (0.5 mM CuCl₂)	100	%	Viability after 24 h incubation
E. coli Viability (1.0 mM CuCl₂)	< 1	%	No living bacteria detectable after 24 h
Non-Toxic Copper Limit (Tissue)	< 250	µg/g	Dry weight in rat bladder tissue (compared to liver reference)
Mean Encrustation Weight (a-C:H/Cu)	1.994	g	After 21 days in vivo (significantly higher than reference group)

Key Methodologies

The study relied on a hybrid deposition technique and rigorous in vitro/in vivo testing:

Hybrid Deposition Process: A hybrid PVD (Physical Vapor Deposition) and PECVD (Plasma Enhanced Chemical Vapor Deposition) process was developed to create the a-C:H/Cu-multilayer coating.
Layer Structure: The coating consisted of alternating layers of a-C:H (DLC) and nanoscale copper, with individual layer thicknesses of approximately 200 nm.
PECVD Parameters (a-C:H): Deposition utilized 7 sccm Ar + 50 sccm C₂H₂ gas flow at 2.3 x 10^-2 Mbar pressure, 250 W RF power, and 230 V bias voltage.
PVD Parameters (Cu): Deposition utilized 50 sccm Ar gas flow at 3.8 x 10^-2 Mbar pressure, 150 W RF power, and 130 V bias voltage.
In Vitro Testing: Biocompatibility was assessed using human non-tumorigenic urothelial HUC-1 cells via MTS assay. Anti-bacterial effect was tested against uropathogenic Escherichia coli HB 101 in synthetic urine.
In Vivo Model: Male Sprague-Dawley rats were used. Implants (2.0 mm beads or platelets) were surgically placed in the urinary bladder for 21 days.
Analysis: Encrustations were analyzed using SEM, EDX mapping (Ca, P, Mg), and Fourier Transform Infrared Spectrometry (FTIR) to confirm composition (struvite, whewellite, protein). Copper levels in tissue, serum, and urine were measured using F-AAS and ICP-MS.

6CCVD Solutions & Capabilities

The research successfully demonstrated the antibacterial potential of copper-doped DLC coatings but was severely limited by surface roughness leading to high encrustation. 6CCVD provides the ideal material solution to decouple the antibacterial function from the encrustation risk.

Applicable Materials for Replication and Extension

To replicate and extend this research, 6CCVD recommends utilizing MPCVD diamond substrates, which offer superior mechanical, chemical, and surface properties compared to the polymer base material (Elastollan) used in the study:

Optical Grade Single Crystal Diamond (SCD): Recommended for achieving the absolute lowest surface roughness (Ra < 1 nm). This material provides the smoothest possible foundation, minimizing nucleation sites for encrustation while maximizing the integrity and adhesion of the subsequent a-C:H/Cu multilayer.
High-Purity Polycrystalline Diamond (PCD): Recommended for scaling up the research or for larger implant prototypes. 6CCVD offers PCD plates/wafers up to 125 mm in diameter, polished to Ra < 5 nm, providing a cost-effective, large-area, ultra-hard substrate.
Boron-Doped Diamond (BDD): For advanced electrochemical studies or applications requiring integrated sensing capabilities, BDD substrates can be provided.

Customization Potential to Overcome Encrustation

The paper explicitly states that the increased roughness of the a-C:H/Cu-multilayer coating is the causal factor for higher encrustation. 6CCVD’s capabilities directly address this challenge:

Research Requirement	6CCVD Solution & Capability	Technical Advantage
Roughness Mitigation	Ultra-Precision Polishing: SCD (Ra < 1 nm) and PCD (Ra < 5 nm) substrates.	Provides an atomically smooth foundation, eliminating the roughness-induced encrustation observed in the study.
Custom Coating Integration	Internal Metalization Services (Cu, Ti, W, etc.):	We can apply the PVD copper layers and assist in optimizing the PECVD DLC deposition onto the diamond substrate, ensuring robust adhesion and controlled release kinetics.
Custom Dimensions	Wafers up to 125 mm (PCD): Thicknesses from 0.1 µm to 500 µm (SCD/PCD).	Supports the production of custom-sized plates or wafers for large-scale in vitro testing or prototype fabrication, exceeding the 2 mm samples used in the rat model.
Substrate Thickness	Substrates up to 10 mm thick:	Allows for the creation of robust, self-supporting diamond components suitable for long-term implant studies (up to 6 weeks or more, as suggested by the authors).

Engineering Support

6CCVD’s in-house PhD team specializes in the material science of MPCVD diamond and thin-film deposition. We can assist researchers and engineers in optimizing the hybrid PVD-PECVD recipe parameters (gas flow, power, bias voltage) to achieve the precise 0.5 mM-1.0 mM copper release profile required for similar Antibacterial Urological Implant projects, ensuring the coating adheres perfectly to the ultra-smooth diamond surface.

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

The insertion of a ureteral stent provides acute care by restoring urine flow and alleviating urinary retention or dysfunction. The problems of encrustation, bacterial colonization and biofilm formation become increasingly important when ureteral stents are left in place for a longer period of time. One way to reduce encrustation and bacterial adherence is to modify the stent surface with a diamond-like carbon coating, in combination with copper doping. The biocompatibilities of the Elastollan® base material and the a-C:H/Cu-mulitilayer coating were tested in synthetic urine. The copper content in bladder tissue was determined by atomic absorption spectroscopy and in blood and in urine by inductively coupled plasma mass spectrometry. Encrustations on the materials were analyzed by scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. A therapeutic window for copper ions of 0.5-1.0 mM was determined to kill bacteria without affecting human urothelial cells. In the rat animal model, it was found that copper release did not reach toxic concentrations in the affecting tissue of the urinary tract or in the blood. The encrustation behavior of the surfaces showed that the roughness of the amorphous carbon layer with the copper doping is probably the causal factor for the higher encrustation.

Tech Support

Original Source

DOI: https://doi.org/10.3390/polym14163324

References

2001 - Study on concretions developed around urinary catheters and mechanisms of renal calculi development [Crossref]
2006 - The role of biofilm infection in urology [Crossref]
2007 - Biofilms—A microbial life perspective: A critical review [Crossref]
2000 - Biofilms and their role in infections in urology [Crossref]
2019 - Innovations in Ureteral Stent Technology [Crossref]
1998 - The effect of urease inhibitors on the encrustation of urethral catheters [Crossref]
2017 - Efficacy of silver/hydrophilic poly(p-xylylene) on preventing bacterial growth and biofilm formation in urinary catheters [Crossref]