In the surgical treatment of pelvic organ prolapse, serious complications associated with polypropylene mesh have led to the search for new materials causing less inflammation and fibrosis. Human umbilical cord mesenchymal stem cells (HUC-MSCs) possess immunomodulatory and angiogenic properties, (1) while Polycaprolactone /Gelatine methacrylate (PCL/GelMA) scaffolds offer a biocompatible niche for cell growth (2).
This experimental in vivo study in rats aimed to evaluate tissue response of a PCL/GelMA hybrid scaffold seeded with HUC-MSCs compared to acellular scaffolds and polypropylene mesh.

32 female Wistar Albino rats (6-8 months old) were divided into 4 groups (n=8/group): 
1. PCL/GelMA + HUC-MSCs; 
2. Polypropylene mesh; 
3. PCL/GelMA scaffold; 
4. Sham /control (with contralateral intact tissues taken as control). 
Optimization of the scaffold biocompatibility and HUC-MSC adhesion was determined to be PCL fiber coated with 5% GelMA according to previous in vitro and in vivo pilot studies.
Each scaffold seeded with 500,000 cultured HUC-MSCs was implanted subcutaneously dorsally adjacent to the scapulae of the rats. After 72 days, rats were sacrificed, and tissue samples were collected for histological analysis for inflammation and fibrosis with Mallory Azan (MA) and Hematoxylin - eosin (HE) staining (3) (Fig.1) Scoring of inflammation and fibrosis is shown in table 1. Statistical analysis using SPSS, including the Kruskal-Wallis test and post-hoc pairwise comparisons. Ethical approval was obtained, and the main study is ongoing.

Histological analysis revealed increased cell coverage of scaffold holes and surrounding connective tissue, along with increased capillaries in scaffold implantation groups. (Fig.1) Inflammation cells (indicated by arrowheads) were present in all experimental groups, but their density and distribution may vary. The Kruskal-Wallis test showed a statistically significant difference in inflammation levels among the groups (p = .001). Group 4 (Sham) exhibited significantly lower inflammation compared to other groups (p < .001).  A statistically significant difference in fibrosis levels was also observed (p = .003). Fibrosis was significantly higher in groups 2 and 3 compared to other groups.  (p < .032). Mean inflammation and fibrosis scores are given in table 1.

The Polypropylene mesh and PCL/GelMA scaffold groups generally showed higher levels of inflammation and fibrosis compared to the Sham and PCL/GelMA with stem cells groups. The Sham group consistently exhibited the lowest levels of inflammation and fibrosis at 72 days post-implantation, as expected. Notably, the PCL/GelMA scaffold cultured with HUC-MSCs demonstrated a tendency towards lower inflammation and fibrosis compared to the Polypropylene mesh (Group 2) and the PCL/GelMA scaffold alone (Group 3), although not always statistically significant in the pairwise comparisons. Specifically, our results show that the PCL/GelMA scaffolds seeded with HUC-MSCs promote less inflammatory response with fibrosis response compared to polypropylene mesh and acellular PCL/GelMA scaffolds in the rat model.

The addition of HUC-MSCs seem to modulate inflammatory response and fibrosis levels on the PCL/GelMA hybrid scaffolds. These findings suggest the potential of biomodulatory role of HUC-MSCs on the tissue response to scaffolds, warranting further investigation.

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