In vitro and in vivo testing of stereolithography (SLA)-manufactured haemocompatible photopolymers for blood pump

A major medical problem of state-of-the-art heart ventricular assist devices (LVADs) is device-induced thrombus formation due to inadequate blood-flow dynamics generated by the blood pump rotor. The latter is a highly complex device, with difficulties during conventional manufacturing through milling or casting. Therefore, the additive manufacturing technology relying on stereo-lithography (SLA) capable of producing parts of significantly increased freedom for a blood-flow-compatible, thrombus-risk-free design was chosen as novel and flexible technology for that type of application. However, as yet state-of-the-art SLA is not suitable to produce fully safe blood-contacting devices. Therefore, the present experiment covered chemical, mechanical, rheological, tribological, and complex biocompatibility characterization in accordance with i.a. ISO 10993 standards, including hemolysis and an acute thrombogenicity blood test on fresh animal blood (both as innovative laboratory tests to avoid animal usage in preclinical studies) with a special focus on testing demonstrators of miniaturized blood pump rotors. The conducted tests indicated acceptable biocompatibility of the material and a slight improvement in biocompatibility with surface modification. Additionally, a high biocompatibility of the tested materials was confirmed. Based on studies and simulations, stereolithography (SLA) as an additive manufacturing technology with significantly increased freedom for a blood-flow-compatible, thrombus-risk-free design was chosen as a novel and flexible technology basis in the 4DbloodROT project to enable future manufacturing of rotors with exceptional biomimetic complexity

In-Vitro Biocompatibility and Hemocompatibility Study of New PET Copolyesters Intended for Heart Assist Devices

(1) Background: The evaluation of ventricular assist devices requires the usage of biocompatible and chemically stable materials. The commonly used polyurethanes are characterized by versatile properties making them well suited for heart prostheses applications, but simultaneously they show low stability in biological environments. (2) Methods: An innovative material-copolymer of poly(ethylene-terephthalate) and dimer linoleic acid—with controlled and reproducible physico-mechanical and biological properties was developed for medical applications. Biocompatibility (cytotoxicity, surface thrombogenicity, hemolysis, and biodegradation) were evaluated. All results were compared to medical grade polyurethane currently used in the extracorporeal heart prostheses. (3) Results: No cytotoxicity was observed and no significant decrease of cells density as well as no cells growth reduction was noticed. Thrombogenicity analysis showed that the investigated copolymers have the thrombogenicity potential similar to medical grade polyurethane. No hemolysis was observed (the hemolytic index was under 2% according to ASTM 756-00 standard). These new materials revealed excellent chemical stability in simulated body fluid during 180 days aging. (4) Conclusions: The biodegradation analysis showed no changes in chemical structure, molecular weight distribution, good thermal stability, and no changes in surface morphology. Investigated copolymers revealed excellent biocompatibility and great potential as materials for blood contacting devices

In Vivo Biocompatibility of an Innovative Elastomer for Heart Assist Devices

Cardiac surgical approaches require the development of new materials regardless of the polyurethanes used for pulsatile blood pumps; therefore, an innovative biomaterial, a copolymer of poly(ethylene terephthalate) and dimer fatty acid (dilinoleic acid) modified with D-glucitol, hereafter referred to as PET/DLA, has been developed, showing non-hemolytic and atrombogenic properties and resistance to biodegradation. The aim of this work was to evaluate in vivo inflammatory responses to intramuscular implantation of PET/DLA biomaterials of different compositions (hard to soft segments). Two copolymers containing 70 and 65 wt.% of hard segments, as in poly(ethylene terephthalate) and dilinoleic acid in soft segments modified with D-glucitol, were used for implantation tests to monitor tissue response. Medical grade polyurethanes Bionate II 90A and Bionate II 55 were used as reference materials. After euthanasia of animals (New Zealand White rabbits, n = 49), internal organs and tissues that contacted the material were collected for histopathological examination. The following parameters were determined: peripheral blood count, blood smear with May Grunwald–Giemsa staining, and serum C-reactive protein (CRPP). The healing process observed at the implantation site of the new materials after 12 weeks indicated normal progressive collagenization of the scar, with an indication of the inflammatory–resorptive process. The analysis of the chemical structure of explants 12 weeks after implantation showed good stability of the tested copolymers in contact with living tissues. Overall, the obtained results indicate great potential for PET/DLA in medical applications; however, final verification of its applicability as a structural material in prostheses is needed

Semi-Quantitative Method of Assessing the Thrombogenicity of Biomaterials Intended for Long-Term Blood Contact

Biomaterials used in cardiosurgical implants and artificial valves that have long-term contact with blood pose a great challenge for researchers due to the induction of thrombogenicity. So far, the assessment of the thrombogenicity of biomaterials has been performed with the use of highly subjective descriptive methods, which has made it impossible to compare the results of various experiments. The aim of this paper was to present a new semi-quantitative method of thrombogenicity assessment based on scanning electron microscope (SEM) images of an adhered biological material deposited on the surfaces of prepared samples. The following biomaterials were used to develop the proposed method: Bionate 55D polyurethane, polyether-ether ketone, Ti6Al7Nb alloy, sintered yttria-stabilized zirconium oxide (ZrO2 + Y2O3), collagen-coated glass, and bacterial cellulose. The samples were prepared by incubating the biomaterials with platelet-rich plasma. In order to quantify the thrombogenic properties of the biomaterials, a TR parameter based on the fractal dimension was applied. The obtained results confirmed that the use of the fractal dimension enables the quantitative assessment of thrombogenicity and the proper qualification of samples in line with an expert’s judgment. The polyurethanes showed the best thrombogenic properties of the tested samples: Bionate 55D (TR = 0.051) and PET-DLA 65% (average TR = 0.711). The ceramics showed the worst thrombogenic properties (TR = 1.846). All the tested materials were much less thrombogenic than the positive control (TR = 5.639)