A world-first treatment approach for pelvic organ prolapse

Hudson Institute researchers have pioneered 3D bioprinted degradable meshes with stem cells for the treatment of pelvic organ prolapse (POP), in the hope of providing a safe, effective solution for millions of women worldwide.

L – R: Kallyanashis Paul and Dr Shayanti Mukherjee, at  Hudson Institute’s 3D printing technology platform

POP is a debilitating condition that affects one in four women globally, across all age groups. When pelvic floor muscles, tissues and ligaments are damaged or weakened (typically due to childbirth), POP can develop and cause the pelvic organs (the bladder, uterus and bowel) to shift or ‘drop’ into the vagina, or sometimes even outside of the body.

Women living with POP can suffer from incapacitating symptoms such as back pain, poor bowel or bladder control and pain during sex. Despite its high global prevalence—affecting up to 60 percent of mothers over the age of 50—there is currently no optimal treatment for the condition.

Non-degradable, synthetic transvaginal meshes have been used in the past to treat POP, and their negative health complications have triggered the banning of sales in numerous countries, including Australia, New Zealand, USA and UK.

The body recognises these non-degradable meshes as foreign objects, causing women chronic pain, inability to have sex and exposure. Pessaries and pelvic floor exercises are first-line conservative management treatments, yet they do not stop POP progression and only manage symptoms. Native tissue surgery is the following treatment alternative, but it has a high failure rate and causes women to undergo multiple surgeries.

An alternative treatment strategy

Hudson Institute researchers recognised the need for a degradable mesh that prevents a negative immune response in women with POP. A study published in Acta Biomaterialia, led by international PhD student Kallyanashis Paul and Dr Shayanti Mukherjee, SIEF John Stocker Postdoctoral Fellow (supported by stem cell biology expert Professor Caroline Gargett and material scientist Professor Jerome Werkmeister), investigated a world-first personalised therapy approach involving a two-step mesh tissue-engineered fabrication process.

First, using Hudson Institute’s 3D printing technology platform, Paul and his multi-disciplinary team printed a custom-made degradable mesh based on a computer aided design (CAD) model. After that, endometrial stem cells—from the lining of a woman’s uterus—were 3D bioprinted on top of the mesh, encased in aloe vera-based hydrogel.

“In this study, we developed a novel plant-based hydrogel for bioprinting therapeutic cells on 3D printed meshes” said Paul, of the Endometrial Stem Cell Biology research group. “Our study is the first to assess the foreign body response to such 3D bioprinted cellular constructs in vivo.”

The 3D printed microstructure meshes provide structural support, whereas the bioprinted stem cells in aloe vera hydrogel help to modulate the interaction with host cells.

“This technology allows designing of meshes with micro-scale fibres in any desired geometry with high precision” commented Dr Mukherjee. “Such structural cues provide a larger surface for cells in the body to integrate with the biomaterial. In addition, the presence of therapeutic cells such as endometrial stem cells prevent an undesirable foreign body response.”

The world-first study, conducted in pre-clinical models, demonstrated a suppressed negative foreign body response to the mesh within one week. This was due to the anti-inflammatory, tissue regenerative environment the mesh promoted. The team hypothesise that this environment could potentially trigger the body to create new proteins to strengthen the vaginal wall.

“There is a huge unmet need for new POP treatments” said Dr Mukherjee. “Biocompatible material designs that provide structural stability with therapeutic cells and provide a good healing environment could be the key to overcoming the hurdles faced with current treatment.”

An effective mesh that prevents negative health complications could allow women to perform daily activities without anxiety or embarrassment of incontinence and body image.

“The 3D printing Cell Therapies and Regenerative Medicine Platform at Hudson Institute offers the opportunity to design and print meshes and therapeutic cells in a good manufacturing practice (GMP) facility” said the team. “In the future, we could design personalised 3D bioprinted surgical constructs for patients based on their specific needs, even using their own cells.”

Future studies will focus on longer term testing, to ensure these promising results can eventually be translated into clinical practice.

Collaborators: Monash Health Translational Medicine, Department of Biochemistry, Monash University, Melbourne Centre for Nanofabrication.

Funders: National Health and Medical Research Council (NHMRC), Science and Industry Endowment Fund, Monash University, Rebecca L Cooper Medical Research Foundation, CASS Foundation and the Victorian Government’s Operational Infrastructure Support Program.

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