Fully absorbable poly-4-hydroxybutyrate implants exhibit more favorable cell-matrix interactions than polypropylene

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Abstract

Pelvic organ prolapse (POP) is a multifactorial condition characterized by the descent of the pelvic organs due to the loss of supportive tissue strength. This is presumably caused by the decreased fibroblast function and the subsequent change in the quality of the extracellular matrix. The correction of POP using an implant intends to provide mechanical support to the pelvic organs and to stimulate a moderate host response. Synthetic polypropylene (PP) implants were commonly used for the correction of prolapse. Although they were successful in providing support, these implants have been associated with clinical complications in the long term due to substantial foreign body response and inappropriate tissue integration. The complications can be avoided or minimized by engineering a biocompatible and fully absorbable implant with optimized mechanical and structural characteristics that favor more appropriate cellular interactions with the implant. Therefore, in this study, we evaluated implants comprised of poly-4-hydroxybutyrate (P4HB), a fully absorbable material with high mechanical strength, as an alternative to PP. The P4HB implants were knitted in four unique designs with different pore shapes ranging from a more rectangular geometry- as it is in PP implant- to a rounded geometry, to determine the effect of the implant structure on the textural and mechanical properties and subsequent cell-matrix interaction. The cellular response was investigated by seeding primary vaginal fibroblasts isolated from patients with POP. P4HB favored cellular functions more than PP, as indicated by greater cell attachment and proliferation (P < 0.01), and significantly more collagen deposition (P4HB vs PP, 11.19 μg vs 6.67 μg) at 28 days culture (P < 0.05). All P4HB implants had higher strength and lower stiffness than the PP scaffold. The material and the design of the implant also influenced the behavior of vaginal fibroblasts. The aspect ratio of the vaginal POP fibroblasts cultured on the PP implant (1.61 ± 0.75) was significantly (P < 0.005) smaller than those cultured on P4HB implants (average 2.31 ± 0.09). The P4HB structure with rounded pores showed the lowest stiffness and highest fibroblast attachment and proliferation (P < 0.01). Overall, P4HB induces more matrix deposition compared to PP and knit design can further optimize cell behavior.

Original languageEnglish
Article number111702
JournalMaterials science and engineering. C: Materials for biological applications
Volume120
Early online date2020
DOIs
Publication statusPublished - Jan 2021

Keywords

  • Fully absorbable
  • Implant
  • Pelvic organ prolapse
  • Poly-4-hydroxybutyrate
  • Vaginal fibroblast

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