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

Abstract

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.

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

“…Previously (9) reported in vitro studies show that 3D printed vascular stent constructs could be iodized, which made these constructs highly resistant to supporting bacterial growth in culture assays. Tappa et al (10) incorporated estrogen and progesterone into 3D printed intrauterine devices which demonstrated the utility of such devices as contraceptives and drug-delivery devices. Such incorporation of drugs and hormones into 3D printed insert spacers represents a novel approach to further ‘customize’ migration/invasion assays using the advantage of 3D printing technologies to study migration and repulsion effects of materials introduced into the inserts used in such 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).…”

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). …”

“…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. In the near future, antibiotic impregnated hardware will be custom printed to deliver therapeutic doses of medication, tailored to the individual.…”