Development of 3D Printed Biodegradable Mesh with Antimicrobial Properties for Pelvic Organ Prolapse.

Jiongyu Ren,Maria A. Woodruff,Rebecca Murray,Jilong Qin,Andrea Warwick,Makrina Totsika,Andrew D. Riddell,Michael Chen,Nicholas Rukin,Cynthia S. Wong

doi:10.3390/polym14040763

Abstract

To address the increasing demand for safe and effective treatment options for pelvic organ prolapse (POP) due to the worldwide ban of the traditional polypropylene meshes, this study introduced degradable polycaprolactone (PCL)/polyethylene glycol (PEG) composite meshes fabricated with melt-electrowriting (MEW). Two PCL/PEG mesh groups: 90:10 and 75:25 (PCL:PEG, wt%) were fabricated and characterized for their degradation rate and mechanical properties, with PCL meshes used as a control. The PCL/PEG composites showed controllable degradation rates by adjusting the PEG content and produced mechanical properties, such as maximal forces, that were higher than PCL alone. The antibacterial properties of the meshes were elicited by coating them with a commonly used antibiotic: azithromycin. Two dosage levels were used for the coating: 0.5 mg and 1 mg per mesh, and both dosage levels were found to be effective in suppressing the growth of S. aureus bacteria. The biocompatibility of the meshes was assessed using human immortalized adipose derived mesenchymal stem cells (hMSC). In vitro assays were used to assess the cell viability (LIVE/DEAD assay), cell metabolic activity (alamarBlue assay) and cell morphology on the meshes (fluorescent and electron microscopy). The cell attachment was found to decrease with increased PEG content. The freshly drug-coated meshes showed signs of cytotoxicity during the cell study process. However, when pre-released for 14 days in phosphate buffered saline, the initial delay in cell attachment on the drug-coated mesh groups showed full recovery at the 14-day cell culture time point. These results indicated that the PCL/PEG meshes with antibiotics coating will be an effective anti-infectious device when first implanted into the patients, and, after about 2 weeks of drug release, the mesh will be supporting cell attachment and proliferation. These meshes demonstrated a potential effective treatment option for POP that may circumvent the issues related to the traditional polypropylene meshes.

Highlights

Pelvic organ prolapse (POP) and incontinence are common and significant problems for women
Data from the Therapeutic Goods Administration (TGA) showed that 151,000 meshes have been implanted in Australia since 1998 [4] and 3.7 million world-wide between 2005 and 2013 [5]
According to TGA data, in 2018 Australia cancelled the approval of all mesh devices placed through the vagina for POP and required all mesh devices to be subject to a comprehensive review before being supplied

Summary

Introduction

Pelvic organ prolapse (POP) and incontinence are common and significant problems for women. Patients with symptoms of urinary and faecal incontinence and POP, were commonly treated via implantation of polypropylene (PP) pelvic meshes [2,3]. Data from the Therapeutic Goods Administration (TGA) showed that 151,000 meshes have been implanted in Australia since 1998 [4] and 3.7 million world-wide between 2005 and 2013 [5]. Complications of pelvic mesh implantation such as erosion into vagina, infection, pain and discomfort were occurring, with some patients requiring further surgery [5]. New Zealand was the first country in the world to ban the use of transvaginal POP mesh products in 2017 and followed by UK in 2018 [8]. The worldwide bans have created a significant unmet clinical need of providing women with good treatment options and viable therapeutics

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Conclusion