Flávia S. C. Rodrigues

Additive manufacturing offers significant opportunities for the development of blood-contacting devices. However, traditional biocompatible materials suitable for material extrusion (ME) often exhibit limited leak-tightness, restricting their application in this field. Acrylonitrile butadiene styrene (ABS) is a widely used thermoplastic valued for its impact resistance, durability, and compatibility with ME technology, making it a promising candidate for functional biomedical components and blood-contacting applications. Although some ABS filaments are marketed as medical grade and assessed for general biocompatibility, their hemocompatibility remains largely untested. This study aims to evaluate the hemocompatibility of ME 3D-printed ABS and to investigate whether acetone post-processing affects its blood-contact properties. Dimensional accuracy, surface roughness, PBS uptake, swelling, and wettability were characterized, and hemocompatibility was assessed through hemolysis, coagulation, and platelet and leukocyte interaction assays before and after acetone treatment, using two ABS filaments, one of which was marketed as medical grade. Hemolysis remained below the hemolytic threshold, indicating that ABS is non-hemolytic. Similarly, clot masses and platelet and leukocyte adhesion were significantly lower than positive controls. However, coagulation assays performed without anticoagulants indicated a time-dependent tendency toward thrombogenesis under static conditions. Acetone post-treatment improved surface smoothness and layer adhesion without adversely affecting hemocompatibility. No significant differences were observed between filament types or between acetone-treated and untreated groups. These findings suggest that 3D-printed ABS is suitable for in vitro and lab-scale blood-contacting applications, particularly when post-processed with acetone, although careful design considerations remain necessary to minimize thrombotic risks.

Zirconium-based metal–organic framework (MOF) NU-1000 was successfully synthesized and exhibited the expected structural and chemical properties, confirming its suitability as an adsorbent for protein-bound uremic toxins (PBUTs). In batch experiments, NU-1000 removed approximately 53% of indoxyl sulfate (IS), corresponding to an adsorption capacity of 17.7 mg IS g⁻¹ NU-1000. To translate this adsorption capability into a membrane platform, mixed matrix membranes (MMMs) were prepared by incorporating NU-1000 into a cellulose acetate (CA) matrix via phase inversion. Structural characterization confirmed the uniform dispersion of NU-1000 microcrystals within the polymer, with no evidence of agglomeration or degradation during fabrication. The resulting membranes exhibited an asymmetric morphology, consisting of a dense selective layer supported by a porous substructure, while maintaining good hydrophilicity (contact angle <60°) and structural integrity. Under crossflow filtration of buffered IS solutions, CA/NU-1000 membranes showed a 1.3-fold increase in IS transport compared to pristine CA membranes. This enhancement indicates that NU-1000 retains its adsorption functionality after incorporation into the polymer matrix and contributes to adsorption-assisted transport. The reversible interactions between IS and NU-1000 enhance solute partitioning within the membrane, promoting diffusion and increasing permeation. Overall, these results demonstrate that CA/NU-1000 MMMs combine the processability and transport properties of conventional polymeric membranes with MOF-based adsorption, offering a promising strategy for adsorption-assisted transport and improved clearance of PBUTs in hemodialysis.

Chronic kidney disease (CKD), a pressing global health issue, affects millions and leads to end-stage renal disease (ESRD). Hemodialysis (HD) is a crucial treatment for ESRD, yet its limited efficiency in removing protein-bound uremic toxins (PBUTs) results in high morbidity and mortality rates. A high affinity of pharmaceutical drugs for human serum albumin (HSA) can be leveraged to compete effectively with PBUTs for the same HSA binding sites, thereby enabling them to be capable of displacing these toxins. One such drug is ibuprofen (IBF), known for its very high affinity for HSA and sharing the same binding site as indoxyl sulfate (IS). This study explores the development of IBF-immobilized cellulose acetate-based (CA-based) thin films. The films were created by reacting CA with IBF-modified silica precursors at varying concentrations. The presence of IBF in CA/TEOS/APTES-IBF-3 and CA/TEOS-IBF-25 films, containing 3 and 25 wt % IBF, respectively, was confirmed through ¹H NMR spectra. Competitive displacement binding assays indicated that while the incorporation of 3 wt % IBF showed no significant enhancement in IS displacement, the 25 wt % IBF film increased the dialyzed IS by 1.3 when normalized to non-IBF films. Furthermore, there was a 1.2-fold decrease in the total percentage of IS, and the free percentage of IS increased 1.3 to 3.0 times. Although direct systemic infusion of IBF in HD patients achieves a 2.4 times higher removal of IS, it is impractical due to the risks it poses to ESRD patients. The IBF-immobilized films offer the advantage of localized binding, thus eliminating the need for systemic exposure. This innovative approach lays a foundation for developing more efficient HD membranes, aiming to address the challenging issue of PBUT elimination and potentially enhance the quality of life and treatment outcomes for ESRD patients.

End-stage renal disease (ESRD) patients rely on renal replacement therapies to survive. Hemodialysis (HD), the most widely applied treatment, is responsible for the removal of excess fluid and uremic toxins (UTs) from blood, particularly those with low molecular weight (MW < 500 Da). The development of high-flux membranes and more efficient treatment modes, such as hemodiafiltration, have resulted in improved removal rates of UTs in the middle molecular weight range. However, the concentrations of protein-bound uremic toxins (PBUTs) remain essentially untouched. Due to the high binding affinity to large proteins, such as albumin, PBUTs form large complexes (MW > 66 kDa) which are not removed during HD and their accumulation has been strongly associated with the increased morbidity and mortality of patients with ESRD. In this review, we describe adsorption- and displacement-based approaches currently being studied to enhance the removal of PBUTs. The development of mixed matrix membranes (MMMs) with selective adsorption properties, infusion of compounds capable of displacing UTs from their binding site on albumin, and competitive binding membranes show promising results, but the road to clinical application is still long, and further investigation is required.

A novel cellulose acetate-based monophasic hybrid skinned amine-functionalized CA-SiO₂-(CH₂)₃NH₂ membrane was synthesized using an innovative method which combines the phase inversion and sol-gel techniques. Morphological characterization was performed by scanning electron microscopy (SEM), and the chemical composition was analyzed by Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR). The characterization of the monophasic hybrid CA-SiO₂-(CH₂)₃NH₂ membrane in terms of permeation properties was carried out in an in-house-built single hemodialysis membrane module (SHDMM) under dynamic conditions. Permeation experiments were performed to determine the hydraulic permeability (Lp), molecular weight cut-off (MWCO) and the rejection coefficients to urea, creatinine, uric acid, and albumin. SEM confirmed the existence of a very thin (2-(CH₂)₃NH₂ membrane were 66.61 kg·h⁻¹·m⁻²·bar⁻¹ and 24.5 kDa, respectively, and that the Lp was 1.8 times higher compared to a pure CA membrane. Furthermore, the CA-SiO₂-(CH₂)₃NH₂ membrane fully permeated urea, creatinine, and uric acid while completely retaining albumin. Long-term filtration studies of albumin solutions indicated that fouling does not occur at the surface of the CA-SiO₂-(CH₂)₃NH₂ membrane.

Vision is the most dominant of our senses, and it is crucial in every stage of our lives. Ocular diseases, regardless of whether they cause vision impairment or not, lead to personal and financial hardships. The anatomy and physiology of the eye strongly limit the efficacy of current ocular drug delivery strategies. Nanotechnology has been the ground for the development of powerful strategies in several fields, namely in medicine. This review highlights emerging nanotechnology-based solutions for improving ocular drug delivery and thus the bioavailability and efficacy of drugs. We focus our review on ambitious but promising approaches currently emerging to leverage the efficacy of nanoparticle-based systems in ocular therapy: (i) light-responsive nanoparticles, which enable spatiotemporal control of drug release; (ii) mesoporous silica nanoparticles, which offer high surface area-to-volume ratio, simple surface modification, good biocompatibility, and improved bioavailability; and (iii) contact lenses, which serve as a compliant method of nanoparticles use and as drug delivery systems for the treatment of ocular diseases.