Fused Deposition Modeling as an Effective Tool for Anti-Infective Dialysis Catheter Fabrication.

Catheter-associated infections are a common complication that occurs in dialysis patients. Current strategies to prevent infection include catheter coatings containing heparin, pyrogallol, or silver nanoparticles, which all have an increased risk of causing resistance in bacteria. Therefore, a novel approach for manufacture, such as the use of additive manufacturing (AM), also known as three-dimensional (3D) printing, is required. Filaments were produced by extrusion using thermoplastic polyurethane (TPU) and tetracycline hydrochloride (TC) in various concentrations (e.g., 0, 0.25, 0.5, and 1%). The extruded filaments were used in a fused deposition modeling (FDM) 3D printer to print catheter constructs at varying concentrations. Release studies in phosphate-buffered saline, microbiology studies, thermal analysis, contact angle, attenuated total reflection-Fourier transform infrared, scanning electron microscopy, and X-ray microcomputer tomography (μCT) analysis were conducted on the printed catheters. The results suggested that TC was uniformly distributed within the TPU matrix. The microbiology testing of the catheters showed that devices containing TC had an inhibitory effect on the growth of Staphylococcus aureus NCTC 10788 bacteria. Catheters containing 1% TC maintained inhibitory effect after 10 day release studies. After an initial burst release in the first 24 h, there was a steady release of TC in all concentrations of catheters. 3D-printed antibiotic catheters were successfully printed with inhibitory effect on S. aureus bacteria. Finally, TC containing catheters showed resistance to S. aureus adherence to their surfaces when compared with catheters containing no TC. Catheters containing 1% of TC showed a bacterial adherence reduction of up to 99.97%. Accordingly, the incorporation of TC to TPU materials can be effectively used to prepare anti-infective catheters using FDM. This study highlights the potential for drug-impregnated medical devices to be created through AM.

[1]  W. Müller,et al.  Drug Delivery From Polymer-Based Nanopharmaceuticals—An Experimental Study Complemented by Simulations of Selected Diffusion Processes , 2019, Front. Bioeng. Biotechnol..

[2]  Niklas Sandler,et al.  Towards fabrication of 3D printed medical devices to prevent biofilm formation. , 2014, International journal of pharmaceutics.

[3]  Eneko Larrañeta,et al.  Synthesis and characterization of hyaluronic acid hydrogels crosslinked using a solvent-free process for potential biomedical applications , 2018, Carbohydrate polymers.

[4]  Wenlei Xiao,et al.  Nonplanar slicing and path generation methods for robotic additive manufacturing , 2018 .

[5]  Manuel Schaffner,et al.  3D Printing of Hierarchical Silk Fibroin Structures. , 2016, ACS applied materials & interfaces.

[6]  Jianzhong Fu,et al.  Printing@Clinic: From Medical Models to Organ Implants. , 2017, ACS biomaterials science & engineering.

[7]  Sarah A. Stewart,et al.  Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications , 2018, Polymers.

[8]  Song Liu,et al.  3D-printed “fistula stent” designed for management of enterocutaneous fistula: An advanced strategy , 2017, World journal of gastroenterology.

[9]  M. Ringer,et al.  An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial. , 1988, The American journal of medicine.

[10]  Dong-Woo Cho,et al.  3D Printed Tissue Models: Present and Future. , 2016, ACS biomaterials science & engineering.

[11]  Simon Gaisford,et al.  Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing. , 2017, International journal of pharmaceutics.

[12]  M. Yu,et al.  Efficacy of subcutaneous silver-impregnated cuffs in preventing central venous catheter infections. , 1996, Chest.

[13]  T. Mah,et al.  Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. , 2017, FEMS microbiology reviews.

[14]  Willie E. Rochefort,et al.  Additive Manufacturing With Soft TPU – Adhesion Strength in Multimaterial Flexible Joints , 2019, Front. Mech. Eng..

[15]  E. Moretti,et al.  Impact of central venous catheter type and methods on catheter-related colonization and bacteraemia. , 2005, The Journal of hospital infection.

[16]  Dieter Roller,et al.  Influence of slicing tools on quality of 3D printed parts , 2016 .

[17]  Trish M. Perl,et al.  Hospital Epidemiology and Infection Control in Acute-Care Settings , 2011, Clinical Microbiology Reviews.

[18]  Udayabhanu M. Jammalamadaka,et al.  Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications , 2015, International journal of nanomedicine.

[19]  R. Martinez,et al.  Micromachining of Polyurethane Membranes for Tissue Engineering Applications. , 2018, ACS biomaterials science & engineering.

[20]  Julian R. Jones,et al.  3D Printing of Biocompatible Supramolecular Polymers and their Composites. , 2016, ACS applied materials & interfaces.

[21]  Jianwei Zhang,et al.  3D Printing of Nonplanar Layers for Smooth Surface Generation , 2019, 2019 IEEE 15th International Conference on Automation Science and Engineering (CASE).

[22]  Marilyn Roberts,et al.  Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance , 2001, Microbiology and Molecular Biology Reviews.

[23]  A. Ofomaja,et al.  Development of sustainable magnetic polyurethane polymer nanocomposite for abatement of tetracycline antibiotics aqueous pollution: Response surface methodology and adsorption dynamics , 2019, Journal of Cleaner Production.

[24]  S. Bourbigot,et al.  Salen based Schiff bases to flame retard thermoplastic polyurethane mimicking operational strategies of thermosetting resin , 2015 .

[25]  David S. Jones,et al.  An Infection-Responsive Approach To Reduce Bacterial Adhesion in Urinary Biomaterials. , 2016, Molecular pharmaceutics.

[26]  Rao Khan,et al.  Characterizing 3D printing in the fabrication of variable density phantoms for quality assurance of radiotherapy. , 2016, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[27]  W. Shao,et al.  Synergistic antibacterial effect of tetracycline hydrochloride loaded functionalized graphene oxide nanostructures , 2018, Nanotechnology.

[28]  David L. Kaplan,et al.  Evolution of Bioinks and Additive Manufacturing Technologies for 3D Bioprinting. , 2016, ACS biomaterials science & engineering.

[29]  K. Neoh,et al.  Inhibition of escherichia coli and proteus mirabilis adhesion and biofilm formation on medical grade silicone surface , 2012, Biotechnology and bioengineering.

[30]  S B Crowe,et al.  Radiological properties of 3D printed materials in kilovoltage and megavoltage photon beams. , 2017, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[31]  R. Morley,et al.  Paediatric vascular access , 2015 .

[32]  Udayabhanu M. Jammalamadaka,et al.  3D Printed Antibiotic and Chemotherapeutic Eluting Catheters for Potential Use in Interventional Radiology: In Vitro Proof of Concept Study. , 2019, Academic radiology.

[33]  Eric Ehler,et al.  Workload implications for clinic workflow with implementation of three-dimensional printed customized bolus for radiation therapy: A pilot study , 2018, PloS one.

[34]  D. Lamprou,et al.  Fused Deposition Modelling as a Potential Tool for Antimicrobial Dialysis Catheters Manufacturing: New Trends vs. Conventional Approaches , 2019, Coatings.

[35]  Vance G. Fowler,et al.  Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management , 2015, Clinical Microbiology Reviews.

[36]  R. Chandra,et al.  Oral controlled and sustained drug delivery systems , 2018 .

[37]  R. Advíncula,et al.  3D Printing of Photocurable Cellulose Nanocrystal Composite for Fabrication of Complex Architectures via Stereolithography. , 2017, ACS applied materials & interfaces.

[38]  S. Gorman,et al.  Role of physiological conditions in the oropharynx on the adherence of respiratory bacterial isolates to endotracheal tube poly(vinyl chloride). , 1997, Biomaterials.

[39]  Marcello Tonelli,et al.  Catheter-related blood stream infections in hemodialysis patients: a prospective cohort study , 2017, BMC Nephrology.

[40]  Nahal Aliheidari,et al.  3D printed highly elastic strain sensors of multiwalled carbon nanotube/thermoplastic polyurethane nanocomposites , 2017 .

[41]  Eneko Larrañeta,et al.  Synthesis and Characterization of Lignin Hydrogels for Potential Applications as Drug Eluting Antimicrobial Coatings for Medical Materials , 2018, ACS sustainable chemistry & engineering.

[42]  N. Sandler,et al.  Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices. , 2016, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[43]  Ahmad Barari,et al.  Post processing for Fused Deposition Modeling Parts with Acetone Vapour Bath , 2016 .

[44]  I. Gosbell Diagnosis and management of catheter‐related bloodstream infections due to Staphylococcus aureus , 2005, Internal medicine journal.

[45]  A. Bandyopadhyay,et al.  Additive manufacturing: scientific and technological challenges, market uptake and opportunities , 2017 .

[46]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[47]  I. Parkin,et al.  Potent Antibacterial Activity of Copper Embedded into Silicone and Polyurethane. , 2015, ACS applied materials & interfaces.

[48]  Yan Shi,et al.  Effectiveness of silver-impregnated central venous catheters for preventing catheter-related blood stream infections: a meta-analysis. , 2014, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[49]  Zengguang Liu,et al.  A critical review of fused deposition modeling 3D printing technology in manufacturing polylactic acid parts , 2019, The International Journal of Advanced Manufacturing Technology.

[50]  Helena Janik,et al.  Fabrication and Characterization of Flexible Medical-Grade TPU Filament for Fused Deposition Modeling 3DP Technology , 2018, Polymers.

[51]  A. Bodenham,et al.  Long-term central venous access. , 2004, British journal of anaesthesia.

[52]  Shoufeng Yang,et al.  Hope versus hype: what can additive manufacturing realistically offer trauma and orthopedic surgery? , 2014, Regenerative medicine.

[53]  R. Mehboob,et al.  Nosocomial infections: Epidemiology, prevention, control and surveillance , 2017 .

[54]  Kock-Yee Law,et al.  Definitions for Hydrophilicity, Hydrophobicity, and Superhydrophobicity: Getting the Basics Right. , 2014, The journal of physical chemistry letters.

[55]  Jennifer L. West,et al.  Electrospun Polyurethane and Hydrogel Composite Scaffolds as Biomechanical Mimics for Aortic Valve Tissue Engineering. , 2016, ACS biomaterials science & engineering.

[56]  J. O. Irwin,et al.  The estimation of the bactericidal power of the blood , 1938, Epidemiology and Infection.

[57]  Udayabhanu M. Jammalamadaka,et al.  Novel Biomaterials Used in Medical 3D Printing Techniques , 2018, Journal of functional biomaterials.

[58]  M. L. Fong,et al.  Antioxidant PLA Composites Containing Lignin for 3D Printing Applications: A Potential Material for Healthcare Applications , 2019, Pharmaceutics.

[59]  Ming Yang,et al.  Blood compatibility of thermoplastic polyurethane membrane immobilized with water-soluble chitosan/dextran sulfate. , 2005, Colloids and surfaces. B, Biointerfaces.

[60]  R. Mülhaupt,et al.  Polymers for 3D Printing and Customized Additive Manufacturing , 2017, Chemical reviews.

[61]  R. Soares,et al.  Designing Biomaterials for 3D Printing. , 2016, ACS biomaterials science & engineering.