| dc.description.abstract | Biomaterials used in implanted medical devices must fulfil a stringent set of requirements, and both the bulk - and the surface properties of a device material must be considered when evaluating the engineering performance of a medical device, where the latter is commonly linked to the potential long term clinical success/failure of the device. The overall aim of the present work was to propose a procedure for risk management with regard to the clinical use of implantable medical devices such as Central Venous Catheters (CVCs), by validating and assessing the in-vitro and in-vivo engineering performance of CVCs. The impact of hemocompatible thin film coatings on the material’s in-vitro engineering performance has also been assessed on substrates of a similar material as the material used in the commercial CVCs. The work performed has been divided into two parts, clearly linked to verify proof of concept and the impact of a surface modification.
In Part I, a modular testbed for the validation and assessment of the in-vitro engineering performance of CVCs have been assembled and later used to predict the in-vivo device performance. Focus has been on testing Peripherally Inserted Central Catheter (PICC lines) manufactured from medical grade polyurethane (PU), with additions of barium sulphate (BaSO4) particles. The testbed consisted of the following modules, i.e., (i) a microenvironmental chamber allowing for controlled conditions during simulation of real-life chemotherapeutic treatments (in-vitro module), (ii) a Chandler Loop model for whole blood exposure (in- vitro module), and (iii) a clinical patient study including breast cancer patients receiving chemotherapeutic treatment (in-vivo module). The PICC lines were artificially aged by exposing them to chemotherapeutic drugs. Additional PICC lines were exposed only to a saline solution (NaCl) with the same flow rate and volume as during the medical treatment protocol to evaluate the impact of the flow of an inert fluid. In the Chandler Loop model, samples exposed to either medical drugs or NaCl, were also exposed to whole blood. The chemical, mechanical, and morphological properties of the device material were evaluated by FE-SEM, FTIR, TGA, hemocompatibility testing, image analysis, and tensile testing. In addition, 50 ex-implanted PU PICC lines exposed to the same chemotherapeutic drugs as in the in-vitro study were also analysed. The obtained in-vitro and in-vivo results were later compared with non-exposed PICC lines used as reference material. Good agreement was established between the in-vitro and in-vivo results in view of decline of engineering performance. Material flake-ups, surface irregularities with clear structural patterns, varying amounts of biological matter on the inner surface, and severe porosity on the outer surface were the primary trends observed. Thus, confirming that the developed testbed and test procedure for generating in-vitro results can be used to predict in-vivo outcomes. The outer surface porosity is linked to the release of additive particles, such as BaSO4, influencing the surface morphology of the device material as it becomes a potential promoting factor for loss of engineering performance.
In Part II, the porosity observed in Part I was addressed through surface modification of medical grade polycarbonate-based aliphatic thermoplastic polyurethane (TPU) (Carbothane) with a 20 wt.% BaSO4 addition, to improve the surface properties of the material. The engineering performance of Ti-based thin film coatings (titanium oxynitrides (TiOxNy)), as well as a Diamond-Like Carbon (DLC) thin film coating, were assessed and compared to non-coated substrates. Radio Frequency (RF) magnetron sputtering, and Direct Current (DC) reactive magnetron sputtering were used to deposit the TiOxNy thin film coatings The commercial DLC coating was deposited by High Impulse Power Magnetron Sputtering (HiPIMS). Non-coated and coated samples were artificially aged in Phosphate-Buffered Saline (PBS) solution, for intervals of 10 min up to 30 days. To evaluate the hemocompatibility, the coated and non-coated substrates were exposed to whole blood in the Chandler Loop model. The developed thin film coating’s morphological and mechanical bulk properties were tested and analysed together with the non-coated reference samples by FE-SEM, contact angle measurements, XPS, TEM, hemocompatibility testing, friction testing, and tensile testing. The liquid samples were analysed by ICP-MS. It was established that improvements to the surface properties relevant for blood-contacting medical devices (i.e., improvements in the material wettability and the surface friction coefficient) were observed by modifying the material surface while maintaining the favourable mechanical behaviour of the bulk material.
The overall conclusion is that medical grade PU is rigorously affected by being exposed to normal human body conditions, as well as by being exposed to chemotherapeutic drugs and whole blood. The changes observed in the morphological structure of the material indicate a loss of particles in the polymer matrix, leaving pores that are potential sites for weakness. This, in turn, will cause premature initiation of surface irregularities resulting in a suboptimal engineering performance. The deposition of the developed thin film coatings proves to be a promising approach to modifying the surface properties relevant for improved hemocompatibility. | en_US |
