Composite mesh design for delivery of autologous mesenchymal stem cells influences mesh integration, exposure and biocompatibility in an ovine model of pelvic organ prolapse
| Autor: | Anna Rosamilia, Michael Ng, Shayanti Mukherjee, Fiona L. Cousins, Jerome A. Werkmeister, Saeedeh Darzi, Stuart Emmerson, Ker Sin Tan, Caroline E. Gargett, Joan Melendez-Munoz, Sharon Lee Edwards, Kishore Bhakoo, Päivi K. Karjalainen |
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| Rok vydání: | 2019 |
| Předmět: |
food.ingredient
Biocompatibility Biophysics Bioengineering 02 engineering and technology Mesenchymal Stem Cell Transplantation Gelatin Pelvic Organ Prolapse Biomaterials 03 medical and health sciences food Tissue engineering In vivo Materials Testing Leukocytes Animals Myofibroblasts 030304 developmental biology 0303 health sciences Pelvic organ Sheep biology Chemistry Composite mesh Mesenchymal stem cell Mesenchymal Stem Cells Muscle Smooth Surgical Mesh 021001 nanoscience & nanotechnology Actins Biomechanical Phenomena Disease Models Animal Nylons Glutaral Mechanics of Materials Vagina Ceramics and Composites biology.protein Female Collagen 0210 nano-technology Elastin Biomedical engineering |
| Zdroj: | Biomaterials. 225:119495 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2019.119495 |
| Popis: | The widespread use of synthetic transvaginal polypropylene mesh for treating Pelvic Organ Prolapse (POP) has been curtailed due to serious adverse effects highlighted in 2008 and 2011 FDA warnings and subsequent legal action. We are developing new synthetic mesh to deliver endometrial mesenchymal stem cells (eMSC) to improve mesh biocompatibility and restore strength to prolapsed vaginal tissue. Here we evaluated knitted polyamide (PA) mesh in an ovine multiparous model using transvaginal implantation and matched for the degree of POP. Polyamide mesh dip-coated in gelatin and stabilised with 0.5% glutaraldehyde (PA/G) were used either alone or seeded with autologous ovine eMSC (eMSC/PA/G), which resulted in substantial mesh folding, poor tissue integration and 42% mesh exposure in the ovine model. In contrast, a two-step insertion protocol, whereby the uncoated PA mesh was inserted transvaginally followed by application of autologous eMSC in a gelatin hydrogel onto the mesh and crosslinked with blue light (PA + eMSC/G), integrated well with little folding and no mesh exposure. The autologous ovine eMSC survived 30 days in vivo but had no effect on mesh integration. The stiff PA/G constructs provoked greater myofibroblast and inflammatory responses in the vaginal wall, disrupted the muscularis layer and reduced elastin fibres compared to PA + eMSC/G constructs. This study identified the superiority of a two-step protocol for implanting synthetic mesh in cellular compatible composite constructs and simpler surgical application, providing additional translational value. |
| Databáze: | OpenAIRE |
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