Blended Nanostructured Degradable Mesh with Endometrial Mesenchymal Stem Cells Promotes Tissue Integration and Anti-Inflammatory Response in Vivo for Pelvic Floor Application

Biomacromolecules. 2019 Jan 14;20(1):454-468. doi: 10.1021/acs.biomac.8b01661. Epub 2018 Dec 18.

Abstract

The current urogynecological clinical meshes trigger unfavorable foreign body response which leads to graft failure in the long term. To overcome the present challenge, we applied a tissue engineering strategy using endometrial SUSD2+ mesenchymal stem cells (eMSCs) with high regenerative properties. This study delves deeper into foreign body response to SUSD2+ eMSC based degradable PLACL/gelatin nanofiber meshes using a mouse model targeted at understanding immunomodulation and mesh integration in the long term. Delivery of cells with nanofiber mesh provides a unique topography that enables entrapment of therapeutic cells for up to 6 weeks that promotes substantial cellular infiltration of host anti-inflammatory macrophages. As a result, degradation rate and tissue integration are highly impacted by eMSCs, revealing an unexpected level of implant integration over 6 weeks in vivo. From a clinical perspective, such immunomodulation may aid in overcoming the current challenges and provide an alternative to an unmet women's urogynecological health need.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants / adverse effects
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Cells, Cultured
  • Endometrium / cytology*
  • Female
  • Gelatin / chemistry
  • Gynecologic Surgical Procedures / instrumentation*
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Polyesters / chemistry
  • Surgical Mesh / adverse effects
  • Tissue Engineering / methods*
  • Tissue Scaffolds / adverse effects
  • Tissue Scaffolds / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Membrane Glycoproteins
  • Polyesters
  • SUSD2 protein, human
  • lactide-caprolactone copolymer
  • Gelatin