Extracellular matrix regenerative graft attenuates the negative impact of polypropylene prolapse mesh on vagina in rhesus macaque.
BACKGROUND
The use of wide pore lightweight polypropylene mesh to improve anatomical outcomes in the surgical repair of prolapse has been hampered by mesh complications. One of the prototype prolapse meshes has been found to negatively impact the vagina by inducing a decrease in smooth muscle volume and contractility and the degradation of key structural proteins (collagen and elastin), resulting in vaginal degeneration. Recently, bioscaffolds derived from extracellular matrix have been used to mediate tissue regeneration and have been widely adopted in tissue engineering applications.


OBJECTIVE
Here we aimed to: (1) define whether augmentation of a polypropylene prolapse mesh with an extracellular matrix regenerative graft in a primate sacrocolpopexy model could mitigate the degenerative changes; and (2) determine the impact of the extracellular matrix graft on vagina when implanted alone.


METHODS
A polypropylene-extracellular matrix composite graft (n = 9) and a 6-layered extracellular matrix graft alone (n = 8) were implanted in 17 middle-aged parous rhesus macaques via sacrocolpopexy and compared to historical data obtained from sham (n = 12) and the polypropylene mesh (n = 12) implanted by the same method. Vaginal function was measured in passive (ball-burst test) and active (smooth muscle contractility) mechanical tests. Vaginal histomorphologic/biochemical assessments included hematoxylin-eosin and trichrome staining, immunofluorescent labeling of α-smooth muscle actin and apoptotic cells, measurement of total collagen, collagen subtypes (ratio III/I), mature elastin, and sulfated glycosaminoglycans. Statistical analyses included 1-way analysis of variance, Kruskal-Wallis, and appropriate post-hoc tests.


RESULTS
The host inflammatory response in the composite mesh-implanted vagina was reduced compared to that following implantation with the polypropylene mesh alone. The increase in apoptotic cells observed with the polypropylene mesh was blunted in the composite (overall P < .001). Passive mechanical testing showed inferior parameters for both polypropylene mesh alone and the composite compared to sham whereas the contractility and thickness of smooth muscle layer in the composite were improved with a value similar to sham, which was distinct from the decreases observed with polypropylene mesh alone. Biochemically, the composite had similar mature elastin content, sulfated glycosaminoglycan content, and collagen subtype III/I ratio but lower total collagen content when compared to sham (P = .011). Multilayered extracellular matrix graft alone showed overall comparable values to sham in aspects of the biomechanical, histomorphologic, or biochemical endpoints of the vagina. The increased collagen subtype ratio III/I with the extracellular matrix graft alone (P = .033 compared to sham) is consistent with an ongoing active remodeling response.


CONCLUSIONS
Mesh augmentation with a regenerative extracellular matrix graft attenuated the negative impact of polypropylene mesh on the vagina. Application of the extracellular matrix graft alone had no measurable negative effects suggesting that the benefits of this extracellular matrix graft occur when used without a permanent material. Future studies will focus on understanding mechanisms.
Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Rui
R
Liang
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
Katrina
K
Knight
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
William
W
Barone
Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA.
Robert W
RW
Powers
Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA.
Alexis
A
Nolfi
Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA.
Stacy
S
Palcsey
Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
Steven
S
Abramowitch
Magee Women Research Institute, University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA. Electronic address: moalpa@mail.magee.edu.
Pamela A
PA
Moalli
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D048091:Guided Tissue Regeneration; D008253:Macaca mulatta; D011126:Polypropylenes; D013526:Surgical Mesh; D054457:Tissue Scaffolds; D014596:Uterine Prolapse / Q000601:surgery*; D014621:Vagina / Q000378:metabolism / Q000601:surgery*
D000199:Actins; D001672:Biocompatible Materials; D024042:Collagen Type I; D024061:Collagen Type III; D006025:Glycosaminoglycans; D011126:Polypropylenes; C013786:A73025; D004549:Elastin
apoptosis; extracellular matrix; function; graft; mechanical properties; pelvic organ prolapse; regeneration; rhesus macaque; smooth muscle; structure; synthetic mesh; vagina