3D Printing of Poloxamer 407 Nanogel Discs and Their Applications in Adjuvant Ovarian Cancer Therapy.

Nanogels are attractive biocompatible materials that enable local delivery of multiple drugs. In this study, we demonstrated that 3D printing technology could be used to precisely construct nanogel discs carrying paclitaxel and rapamycin. 3D-printed nanogel disc rounds (12 mm diameter × 1 mm thickness) carrying paclitaxel and rapamycin evaded premature gelation during storage and the initial burst release of the drugs in the dissolution medium. In vivo 3D-printed nanogel discs permitted successful intraperitoneal delivery of paclitaxel and rapamycin in ES-2-luc ovarian-cancer-bearing xenograft mice. They were also shown to be therapeutically effective and capable of preventing postsurgical peritoneal adhesions in the treated xenograft mice.

3D Printed Antibiotic and Chemotherapeutic Eluting Catheters for Potential Use in Interventional Radiology: In Vitro Proof of Concept Study.

RATIONALE AND OBJECTIVES: Additive manufacturing may be used as a form of personalized medicine in interventional radiology by allowing for the creation of customized bioactive constructs such as catheters that can act as a form of localized drug delivery. The purpose of the present in vitro study was to use three-dimensional (3D) printing to construct bioactive-laden bioabsorbable catheters impregnated with antibiotics and chemotherapeutics. MATERIALS AND METHODS: Polylactic acid bioplastic pellets were coated with the powdered bioactive compounds gentamicin sulfate (GS) or methotrexate (MTX) to incorporate these drugs into the 3D printed constructs. The pellets were then extruded into drug-impregnated filament for fused deposition modeling 3D printing. Computer-aided design files were generated in the shapes of 14-F catheters. Scanning electron microscope imaging was used to visualize the presence of the additive powders on the surface of the printed constructs. Elution profiles were run on the antibiotic-laden catheter and MTX-laden catheters. Antibiotic-laden catheters were tested on bacterial broth and plate cultures. RESULTS: Both GS and MTX catheter constructs had sustained drug release up to the 5-day limit of testing. The 3D printed GS-enhanced catheters inhibited all bacterial growth in broth cultures and had an average zone of inhibition of 858 ± 118 mm2 on bacterial plates, whereas control catheters had no effect. CONCLUSION: The 3D printing manufacturing method to create instruments in percutaneous procedures is feasible. Further in vivo studies will substantiate these findings.

Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study.

3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process-suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.

Performance evaluation of nanoclay enriched anti-microbial hydrogels for biomedical applications.

A major factor contributing to the failure of orthopedic and orthodontic implants is post-surgical infection. Coating metallic implant surfaces with anti-microbial agents has shown promise but does not always prevent the formation of bacterial biofilms. Furthermore, breakdown of these coatings within the human body can cause release of the anti-microbial drugs in an uncontrolled or unpredictable fashion. In this study, we used a calcium alginate and calcium phosphate cement (CPC) hydrogel composite as the base material and enriched these hydrogels with the anti-microbial drug, gentamicin sulfate, loaded within a halloysite nanotubes (HNTs). Our results demonstrate a sustained and extended release of gentamicin from hydrogels enriched with the gentamicin-loaded HNTs. When tested against the gram-negative bacteria, the hydrogel/nanoclay composites showed a pronounced zone of inhibition suggesting that anti-microbial doped nanoclay enriched hydrogels can prevent the growth of bacteria. The release of gentamicin sulfate for a period of five days from the nanoclay-enriched hydrogels would supply anti-microbial agents in a sustained and controlled manner and assist in preventing microbial growth and biofilm formation on the titanium implant surface. A pilot study, using mouse osteoblasts, confirmed that the nanoclay enriched surfaces are also cell supportive as osteoblasts readily, proliferated and produced a type I collagen and proteoglycan matrix.

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

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.

Osteoinductive calcium phosphate clay nanoparticle bone cements (CPCs) with enhanced mechanical properties.

Calcium phosphate cements (CPCs) with osteoconductive properties are limited in their applications because of their poor mechanical properties. This study investigated the additive effect of Dexamethasone-doped Halloysite Nanotubes (HNTs on the mechanical properties of CPCs. HNTs are nanosized tubes with alumino-silicate composition. Physico-chemical properties, cytocompatability and cellular functionality of the nanocomposites were assayed. Results suggest that these nanoenhanced composites have a huge potential to broaden the applications of CPCs.

Design and evaluation of a nanoenhanced anti-infective calcium phosphate bone cements.

Post-operative complications due to infections are the most common problems that occur following dental and orthopedic implant surgeries and bone repair procedures. Preventing post-surgical infections is therefore a critical need that current polymethylmethacrylate (PMMA) bone cement fail to address. Calcium phosphate cements (CPCs) are unique in their ability to crystallize calcium and phosphate salts into hydroxyapatite (HA) and hence is naturally osteoconductive. Due to its low mechanical strength its use in implant fixation and bone repair is limited to non-load bearing applications. The present work describes a new and novel antibiotic-doped clay nanotube CPC composite with enhanced mechanical properties as well as sustained release properties.