Rational engineering and design 3D printed meshes with biofunctional assessment for Pelvic Reconstructive Surgery: A pre-clinical assessment

Paul K1, Darzi S2, Hennes D3, O'Connell C4, Gargett C2, Rosamilia A5, Werkmeister J2, Mukherjee S2

Research Type

Pure and Applied Science / Translational

Abstract Category

Research Methods / Techniques

Abstract 769
Open Discussion ePosters
Scientific Open Discussion Session 108
Friday 25th October 2024
12:45 - 12:50 (ePoster Station 4)
Exhibition Hall
Pre-Clinical testing Pelvic Organ Prolapse Stem Cells / Tissue Engineering Basic Science Biomechanics
1. Hudson Intitute of Medical Research, 2. Hudson Institute of Medical Research, 3. Monash University, 4. RMIT University, 5. Monash Health
Presenter
Links

Abstract

Hypothesis / aims of study
Pelvic organ prolapse (POP) is a debilitating urogynaecological condition caused by the descent of the pelvic organs, namely, the uterus, bladder or bowel, affecting more than 50% of women at the post-menopausal stage for whom surgical reconstruction is the only treatment option. In clinics, non-degradable monolayer-knitted meshes such as polypropylene (PP) meshes have widespread applications for treating POP. However, given the adverse events including mesh erosion and pain, non-degradable meshes have been
banned from their clinical applications restoring bladder/bowel functions by the regulatory authorities in several countries namely Australia, New Zealand, USA and UK. In literature, mesh-related adverse events are associated with the in vivo deformation of meshes
represented by pore collapsing that leads to tissue-degenerative foreign body reactions, thereby chronic inflammation. 
In this study, we developed degradable surgical implants using the state-of-the-art 3D printing process called melt electrowriting (MEW) printing. We investigated the impact of distinct mesh geometries and porosities to attribute compatible mechanical tensile strength leading to tissue regenerative cellular events, thereby, inducing favourable foreign body response. Necessary customisations were incorporated during the printing process for specific transvaginal surgical applications restoring bladder or bowel functioning.
Study design, materials and methods
3D Printing parameters were optimised at melting temperature 100OC, voltage (V): 5 KV, nozzle to workspace: ~10 mm, extrusion pressure (P): 8 KPa and printing speed at 10 mm/s. Poly ε-caprolactone (PCL) meshes were fabricated by two-way stacking the fibres at spacing: 1 mm and 0.5 mm at 3 different interlayer angles of 90, 45 and 22.5 degrees (deg). The deformation of the meshes under tension was assessed under tensile cyclic loading. The mesh’s functionalities were assessed by corresponding toughness measurement, and the pore-collapsing was measured by Poisson’s ratio, quantifying the extent of lateral contraction. Considering surgical application, we assessed cellular interaction after seeding vaginal fibroblasts in vitro. The meshes were implanted in a mouse model of POP to assess the foreign body reaction at 1 and 6 weeks.
Results
The morphologic study by electron microscopy reveals the fibre diameter to be 18.86 ± 2.16 µm. The most excellent functionalities were measured for the smallest 22.5-deg angular meshes (19.7 Jm-3) with the least deformation (3%), sustaining structural integrity under tensile stretch. Cellular interaction using vaginal fibroblasts in vitro showed better proliferation of the cells for the smaller angular meshes; printed at 45 and 22.5 deg.
Interpretation of results
Tissue explants with the smallest 22.5-deg angular meshes showed the greatest recruitment of anti- inflammatory CD206+ macrophages at 1 week followed by immune suppression at 6 weeks in vivo leading to better tissue integration.
Concluding message
Emerging engineering technology enables rational design and engineering of implants that in turn allow immunomodulation in host tissue which can be highly beneficial to overcome current hurdles in the field of vaginal mesh surgery.
Disclosures
Funding MRFF And NHMRC Australia Clinical Trial No Subjects Animal Species Mouse, sheep Ethics Committee Monash Medical Committee
14/11/2024 03:27:06