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3D Bioprinted Endometrial Stem Cells on Melt Electrospun PCL Meshes for Pelvic Floor Application Promote Anti-Inflammatory Responses in Mice

41 Pages Posted: 14 May 2019 First Look: Accepted

See all articles by Kallyanashis Paul

Kallyanashis Paul

Hudson Institute of Medical Research - The Ritchie Centre; Monash University - Department of Obstetrics and Gynaecology

Saeedeh Darzi

Hudson Institute of Medical Research - The Ritchie Centre

Gordon Mcphee

Monash University - Monash Health Translation Precinct (MHTP)

Mark Del Borgo

Monash University - Department of Biochemistry and Molecular Biology

Jerome A. Werkmeister

Hudson Institute of Medical Research - The Ritchie Centre; Monash University - Department of Obstetrics and Gynaecology

Caroline E. Gargett

Hudson Institute of Medical Research - The Ritchie Centre; Monash University - Department of Obstetrics and Gynaecology

Shayanti Mukherjee

Hudson Institute of Medical Research - The Ritchie Centre; Monash University - Department of Obstetrics and Gynaecology

Abstract

Endometrial mesenchymal stem/stromal cells (eMSCs) exhibit excellent regenerative capacity in the endometrial lining of the uterus following menstruation and high proliferative capacity in vitro. Bioprinting eMSCs onto a mesh could be a potential therapy for Pelvic Organ Prolapse (POP). This study reports a novel strategy targeting vaginal repair using bioprinting of eMSCs encapsulated in a hydrogel and3D melt electrospun mesh to generate a tissue engineering construct. Following a CAD, 3D printed poly ε-caprolactone (PCL) meshes were fabricated using melt electrospinning (MES) at different temperatures using a GMP clinical grade GESIM Bioscaffolder. Electron and atomic force microscopies revealed that MES meshes fabricated at 100°C and with a speed 20 mm/sec had the largest open pore diameter (47.2 ± 11.4 μm) and the lowest strand thickness (121.4 ± 46 μm) that promoted optimal eMSC attachment. An Aloe Vera-Sodium Alginate (AV-ALG) composite based hydrogel was optimised to a 1:1 mixture (1%AV-1%ALG) and eMSCs, purified from human endometrial biopsies, were then bioprinted in this hydrogel onto the MES printed meshes. Acute in vivo foreign body response assessment in NSG mice revealed that eMSC printed on MES constructs promoted tissue integration, eMSC retention and an anti-inflammatory M2 macrophage phenotype characterised by F4/80+CD206+ colocalization. Our results address an unmet medical need highlighting the potential of alternative 3D bioprinted eMSC-MES meshes as a novel approach to overcome the current challenges with non-degradable knitted meshes in POP treatment.

Keywords: Endometrial mesenchymal stem/stromal cells (eMSCs), melt electrospinning (MES), bioprinting, anti-inflammatory responses, pelvic organ prolapse (POP)

Suggested Citation

Paul, Kallyanashis and Darzi, Saeedeh and Mcphee, Gordon and Borgo, Mark Del and Werkmeister, Jerome A. and Gargett, Caroline E. and Mukherjee, Shayanti, 3D Bioprinted Endometrial Stem Cells on Melt Electrospun PCL Meshes for Pelvic Floor Application Promote Anti-Inflammatory Responses in Mice (May 13, 2019). Available at SSRN: https://ssrn.com/abstract=3387674

Kallyanashis Paul

Hudson Institute of Medical Research - The Ritchie Centre

27-31 Wright Street
Clayton, Victoria 3168
Australia

Monash University - Department of Obstetrics and Gynaecology

Clayton, Victoria 3800
Australia

Saeedeh Darzi

Hudson Institute of Medical Research - The Ritchie Centre

27-31 Wright Street
Clayton, Victoria 3168
Australia

Gordon Mcphee

Monash University - Monash Health Translation Precinct (MHTP)

Clayton, Victoria 3168
Australia

Mark Del Borgo

Monash University - Department of Biochemistry and Molecular Biology

Clayton, Victoria
Australia

Jerome A. Werkmeister

Hudson Institute of Medical Research - The Ritchie Centre

27-31 Wright Street
Clayton, Victoria 3168
Australia

Monash University - Department of Obstetrics and Gynaecology

Clayton, Victoria 3800
Australia

Caroline E. Gargett

Hudson Institute of Medical Research - The Ritchie Centre

27-31 Wright Street
Clayton, Victoria 3168
Australia

Monash University - Department of Obstetrics and Gynaecology

Clayton, Victoria 3800
Australia

Shayanti Mukherjee (Contact Author)

Hudson Institute of Medical Research - The Ritchie Centre ( email )

27-31 Wright Street
Clayton, Victoria 3168
Australia

Monash University - Department of Obstetrics and Gynaecology ( email )

Clayton, Victoria 3800
Australia

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