MP52-08 MACROPHAGE THERAPY VIA COLLAGEN BIOTEXTILE FOR THE TREATMENT OF STRESS URINARY INCONTINENCE

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II (MP52)1 Sep 2021MP52-08 MACROPHAGE THERAPY VIA COLLAGEN BIOTEXTILE FOR THE TREATMENT OF STRESS URINARY INCONTINENCE Ilaha Isali, Snigdha Cingireddi, Phillip McClellan, Mukesh Jain, James Anderson, Ozan Akkus, and Adonis Hijaz Ilaha IsaliIlaha Isali More articles by this author , Snigdha CingireddiSnigdha Cingireddi More articles by this author , Phillip McClellanPhillip McClellan More articles by this author , Mukesh JainMukesh Jain More articles by this author , James AndersonJames Anderson More articles by this author , Ozan AkkusOzan Akkus More articles by this author , and Adonis HijazAdonis Hijaz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002082.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent reviews1,2 proposed the use of macrophages (MΦ) for regenerative purposes either by way of modifying biomaterials to attract host macrophages, or by direct delivery of MΦ. We have demonstrated the polarization of M0 macrophages to the pro-regenerative subtype-M2 upon seeding on genipin crosslinked collagen scaffold (GES). Current study aimed assess the long-term tissue response and post-surgical mechanical properties of implanted GES seeded with M0, M1, and M2 in a rat model. METHODS: Monocytes were harvested from rat bone-marrow. M0, M1 or M2 macrophages were polarized from monocytes and MΦ subtypes were confirmed by flow cytometry. Electrochemically aligned collagen threads were filament wound to produce small collagen scaffold genipin crosslinked. M0, M1 or M2 macrophages were seeded on GES and implanted subcutaneously in rats to determine whether MΦ supplementation improves the stiffness (i.e modulus) of regenerated tissue, collagen deposition by host, and alters the biology of healing. Implants were recovered at 3 months following which they were tested in tension, cellularity was quantified in H&E-stained sections, collagen production was quantified by automated image analysis of Masson’s trichrome sections, and fibrous capsule thickness was measured. RESULTS: M2-subtype seeded scaffolds (GES+M2) had the greatest modulus such that its magnitude was about 2.5 times greater than that of cell-free scaffolds (GES) whereas modulus of GES+M0 or GES+M1 did not differ significantly from that of cell-free scaffolds. Number of cells counts per unit area was the greatest for GES+M2 group, suggesting a greater degree of host cell attraction. Furthermore, alpha smooth muscle actin, a marker of myofibroblasts, was more notably present in M2-seeded scaffolds. M2 delivery induced greater amount of collagen deposition while limiting fibrous encapsulation of the scaffold. Net effect of M2-delivery was such that improved healing biomechanics that converged closer to the 3-5 MPa native tissue modulus range that the scaffold alone is unable to converge. CONCLUSIONS: In vivo delivery of M2-subtype by filament wound collagen scaffolds results in superior healing biomechanics and implant remodelling in comparison to other macrophage subtypes. Source of Funding: This work is supported by NIH grant: R21HD095439-01