Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications

Abstract

Three-dimensional (3D) printing and additive manufacturing holds potential for highly personalized medicine, and its introduction into clinical medicine will have many implications for patient care. This paper demonstrates the first application of 3D printing as a method for the potential sustained delivery of antibiotic and chemotherapeutic drugs from constructs for patient treatment. Our design is focused on the on-demand production of anti-infective and chemotherapeutic filaments that can be used to create discs, beads, catheters, or any medical construct using a 3D printing system. The design parameters for this project were to create a system that could be modularly loaded with bioactive agents. All 3D-printed constructs were loaded with either gentamicin or methotrexate and were optimized for efficient and extended antibacterial and cancer growth-inhibiting cytostatic activity. Preliminary results demonstrate that combining gentamicin and methotrexate with polylactic acid forms a composite possessing a superior combination of strength, versatility, and enhanced drug delivery. Antibacterial effects and a reduction in proliferation of osteosarcoma cells were observed with all constructs, attesting to the technical and clinical viability of our composites. In this study, 3D constructs were loaded with gentamicin and methotrexate, but the method can be extended to many other drugs. This method could permit clinicians to provide customized and tailored treatment that allows patient-specific treatment of disease and has significant potential for use as a tunable drug delivery system with sustained-release capacity for an array of biomedical applications.

Clinical Applications of 3D Printing

“…Implants and procedural devices, take advantage of the customizability, manufacturing capabilities, and potential low cost of additive manufacturing techniques. 3D printing not only allows implants and procedural tools to be tailored to patient-specific anatomy, it allows products to be manufactured with bland or drug-impregnated materials (56-59). 3D printed biologically active implants are discussed in the Bioprinting Revolution section.…”

“…Bioprinting involves the use of various techniques, such as fused deposition modeling, to print bioactive scaffolds impregnated with growth factors designed to stimulate regeneration or drugs that concentrate their activity in the microenvironment, print customized bioactive implants and devices on demand, even generate customized living tissues (56-59, 101, 102). …”

“…Bioactive printing falls under the spectrum of bioprinting, but focuses on using biocompatible plastics, such as polylactic acid, and fused deposition modeling or other 3D printing techniques to create 3D printed implants impregnated with drugs, hormones, or other agents. Weisman et al (56) reported on 3D printed gentamicin- and methotrexate-eluting beads and constructs that showed favorable elution profiles. In an in vitro model, Tappa et al (59) 3D printed gynecologic implants such as intrauterine devices with estrogen and progesterone incorporated into the construct’s structure.…”

“…More relevant to radiologists, custom designed bioactive catheters and stents using absorbable and non-absorbable biocompatible materials are forthcoming applications of 3D printing (56, 57). Weisman et al (57) 3D-printed a bioactive catheter modeled after a commercial drainage catheter and showed similar bacterial and tumor retarding abilities and elution profiles.…”

Three-Dimensional Printing of Cell Exclusion Spacers (CES) for Use in Motility Assays

“…3D printing is projected to be a disruptive manufacturing technology, which may enable labs around the world to fabricate custom assays in house and on-demand. 3D printing technologies also have ability to easily incorporate many bioactive test substances including antibiotics, chemotherapeutics, and hormones either as a pre-print additive or a post-print binder (4–10). These compositional and surface modifications allow highly complex models to be created which can even incorporate bioprinting (11,12).…”