Naşide Mangır1, Christopher J Hillary1, Christopher R Chapple2, Sheila MacNeil3. 1. Department of Materials Science Engineering, Kroto Research Institute, University of Sheffield, UK; Royal Hallamshire Hospital, Department of Urology, Sheffield, UK. 2. Royal Hallamshire Hospital, Department of Urology, Sheffield, UK. 3. Department of Materials Science Engineering, Kroto Research Institute, University of Sheffield, UK. Electronic address: s.macneil@sheffield.ac.uk.
Abstract
BACKGROUND: Polypropylene meshes cause severe complications in some patients. Materials that are biomechanically compatible and can better integrate into host tissues are urgently needed. OBJECTIVE: To design an oestradiol-releasing electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate new extracellular matrix and new blood vessel formation. DESIGN, SETTING, AND PARTICIPANTS: Human adipose derived mesenchymal cells (ADMSC) were isolated from fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10% oestradiol were constructed and used for in vitro and in vivo experiments. INTERVENTION: The angiogenic potential of the fibrous meshes was evaluated using an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Oestradiol release was measured fluorometrically. The effect of fibrous meshes on proliferation and extracellular matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical properties were tested using a tensiometer. RESULTS AND LIMITATIONS: The ultrastructure of the mesh was not affected by the inclusion of oestradiol and mechanical properties were only slightly modified. Oestradiol was released from PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes produced more ECM involving collagen I, collagen III, and elastin. Oestradiol-releasing meshes doubled new blood vessel formation in the chorioallantoic membrane assay (p=0.001) and outgrowth of pro-angiogenic cells in the aortic arch assay (p=0.001). Further studies in longer-term animal models are required to confirm these results. CONCLUSIONS: Oestradiol-releasing PLA meshes increase ECM production and stimulate angiogenesis. As such, they are promising candidate materials to be used in pelvic floor repair and to improve the initial healing phase of a repair material following implantation. PATIENT SUMMARY: In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients' tissues and merit further study in physiologically relevant animal models. Crown
BACKGROUND:Polypropylene meshes cause severe complications in some patients. Materials that are biomechanically compatible and can better integrate into host tissues are urgently needed. OBJECTIVE: To design an oestradiol-releasing electrospun poly-l-lactic acid (PLA) mesh and evaluate its ability to stimulate new extracellular matrix and new blood vessel formation. DESIGN, SETTING, AND PARTICIPANTS: Human adipose derived mesenchymal cells (ADMSC) were isolated from fat. PLA meshes with micro- to nano-sized fibres containing 1%, 5%, and 10% oestradiol were constructed and used for in vitro and in vivo experiments. INTERVENTION: The angiogenic potential of the fibrous meshes was evaluated using an in vivo chorioallantoic membrane and an in vitro chick aortic arch assays. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Oestradiol release was measured fluorometrically. The effect of fibrous meshes on proliferation and extracellular matrix (ECM) production of ADMSC was assessed using immunohistology. Mechanical properties were tested using a tensiometer. RESULTS AND LIMITATIONS: The ultrastructure of the mesh was not affected by the inclusion of oestradiol and mechanical properties were only slightly modified. Oestradiol was released from PLA meshes over a 5-mo period. ADMSCs cultured on oestradiol-releasing PLA meshes produced more ECM involving collagen I, collagen III, and elastin. Oestradiol-releasing meshes doubled new blood vessel formation in the chorioallantoic membrane assay (p=0.001) and outgrowth of pro-angiogenic cells in the aortic arch assay (p=0.001). Further studies in longer-term animal models are required to confirm these results. CONCLUSIONS:Oestradiol-releasing PLA meshes increase ECM production and stimulate angiogenesis. As such, they are promising candidate materials to be used in pelvic floor repair and to improve the initial healing phase of a repair material following implantation. PATIENT SUMMARY: In this study, we designed a tissue engineered material to be used to support weakened pelvic floor tissues in women to avoid the complications associated with current surgical mesh. Our results showed that this material can stimulate new blood vessel formation in simple chick assays and tissue production in vitro. Both properties should help with the integration of this material into patients' tissues and merit further study in physiologically relevant animal models. Crown