TY - JOUR
T1 - Absorbable Electrospun Poly-4-hydroxybutyrate Scaffolds as a Potential Solution for Pelvic Organ Prolapse Surgery
AU - Verhorstert, Kim
AU - Gudde, Aksel
AU - Weitsz, Carmen
AU - Bezuidenhout, Deon
AU - Roovers, Jan-Paul
AU - Guler, Zeliha
N1 - Funding Information: This publication is part of the project “Development of a novel wound healing implant with mechano-stimulation and localized delivery” with project number 17349 of the research program VENI Talent Scheme which is financed by the Dutch Research Council (NWO). Publisher Copyright: © 2022 American Chemical Society. All rights reserved.
PY - 2022/11/21
Y1 - 2022/11/21
N2 - Women with pelvic organ prolapse (POP) have bothersome complaints that significantly affect their quality of life. While native tissue repair is associated with high recurrence rates, polypropylene knitted implants have caused specific implant-related adverse events that have detrimental, often irreversible, effects. We hypothesize that surgical outcome can be improved with a tissue-engineered solution using an absorbable implant that mimics the natural extracellular matrix (ECM) structure, releases estrogen, and activates collagen metabolism by fibroblasts as the main regulators of wound healing. To this aim, we produced electrospun poly-4-hydroxybutyrate (P4HB) scaffolds and biofunctionalized them with estradiol (E2). The cell-implant interactions relevant for POP repair were assessed by seeding primary POP vaginal fibroblasts isolated from patients on electrospun P4HB scaffolds with 1%, 2%, or 5% E2 and without E2. To test our hypothesis on whether ECM mimicking structures should improve regeneration, electrospun P4HB was compared to knitted P4HB implants. We evaluated vaginal fibroblast proliferation, ECM deposition, and metabolism by quantification of collagen, elastin, and matrix metalloproteinases and by gene expression analysis for 28 days. We established effective E2 drug loading with a steady release over time. Significantly higher cell proliferation, collagen-, and elastin deposition were observed on electrospun P4HB scaffolds as compared to knitted P4HB. For this study, physical properties of the scaffolds were more determinant on the cell response than the release of E2. These results indicate that making these electrospun P4HB scaffolds E2-releasing appears to be technically feasible. In addition, electrospun P4HB scaffolds promote the cellular response of vaginal fibroblasts and further studies are merited to assess if their use results in improved surgical outcomes in case of POP repair.
AB - Women with pelvic organ prolapse (POP) have bothersome complaints that significantly affect their quality of life. While native tissue repair is associated with high recurrence rates, polypropylene knitted implants have caused specific implant-related adverse events that have detrimental, often irreversible, effects. We hypothesize that surgical outcome can be improved with a tissue-engineered solution using an absorbable implant that mimics the natural extracellular matrix (ECM) structure, releases estrogen, and activates collagen metabolism by fibroblasts as the main regulators of wound healing. To this aim, we produced electrospun poly-4-hydroxybutyrate (P4HB) scaffolds and biofunctionalized them with estradiol (E2). The cell-implant interactions relevant for POP repair were assessed by seeding primary POP vaginal fibroblasts isolated from patients on electrospun P4HB scaffolds with 1%, 2%, or 5% E2 and without E2. To test our hypothesis on whether ECM mimicking structures should improve regeneration, electrospun P4HB was compared to knitted P4HB implants. We evaluated vaginal fibroblast proliferation, ECM deposition, and metabolism by quantification of collagen, elastin, and matrix metalloproteinases and by gene expression analysis for 28 days. We established effective E2 drug loading with a steady release over time. Significantly higher cell proliferation, collagen-, and elastin deposition were observed on electrospun P4HB scaffolds as compared to knitted P4HB. For this study, physical properties of the scaffolds were more determinant on the cell response than the release of E2. These results indicate that making these electrospun P4HB scaffolds E2-releasing appears to be technically feasible. In addition, electrospun P4HB scaffolds promote the cellular response of vaginal fibroblasts and further studies are merited to assess if their use results in improved surgical outcomes in case of POP repair.
KW - absorbable
KW - electrospinning
KW - estradiol
KW - implant
KW - mesh
KW - pelvic organ prolapse (POP)
KW - poly-4-hydroxybutyrate (P4HB)
KW - scaffold
UR - http://www.scopus.com/inward/record.url?scp=85141519791&partnerID=8YFLogxK
U2 - https://doi.org/10.1021/acsabm.2c00691
DO - https://doi.org/10.1021/acsabm.2c00691
M3 - Article
C2 - 36315937
SN - 2576-6422
VL - 5
SP - 5270
EP - 5280
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 11
ER -