Poly (L-Lactic Acid) Cell-Laden Scaffolds Applied on Swine Model of Tracheal Fistula.

INTRODUCTION: Tracheal fistula (TF) treatments may involve temporary orthosis and further ablative procedures, which can lead to infection. Thus, TF requires other therapy alternatives development. The hypothesis of this work was to demonstrate the feasibility of a tissue-engineered alternative for small TF in a preclinical model. Also, its association with suture filaments enriched with adipose tissue-derived mesenchymal stromal stem cells (AT-MSCs) was assessed to determine whether it could optimize the regenerative process. METHODS: Poly (L-Lactic acid) (PLLA) membranes were manufactured by electrospinning and had morphology analyzed by scanning electron microscopy. AT-MSCs were cultured in these scaffolds and in vitro assays were performed (cytotoxicity, cellular adhesion, and viability). Subsequently, these cellular constructs were implanted in an animal small TF model. The association with suture filaments containing attached AT-MSCs was present in one animal group. After 30 d, animals were sacrificed and regenerative potential was evaluated, mainly related to the extracellular matrix remodeling, by performing histopathological (Hematoxylin-Eosin and trichrome Masson) and immunohistochemistry (Collagen I/II/III, matrix metalloproteinases-2, matrix metalloproteinases-9, vascular endothelial growth factor, and interleukin-10) analyses. RESULTS: PLLA membranes presented porous fibers, randomly oriented. In vitro assays results showed that AT-MSCs attached were viable and maintained an active metabolism. Swine implanted with AT-MSCs attached to membranes and suture filaments showed aligned collagen fibers and a better regenerative progress in 30 d. CONCLUSIONS: PLLA membranes with AT-MSCs attached were useful to the extracellular matrix restoration and have a high potential for small TF treatment. Also, their association with suture filaments enriched with AT-MSCs was advantageous.

Mesenchymal stromal cells from adipose tissue attached to suture material enhance the closure of enterocutaneous fistulas in a rat model.

BACKGROUND AIMS: Surgical treatment for enterocutaneous fistulas (EF) frequently fails. Cell therapy may represent a new approach to treatment. Mesenchymal stromal cells (MSCs) have high proliferative and differentiation capacity. This study aimed to investigate whether MSCs could adhere to suture filament (SF), promoting better EF healing. METHODS: MSCs, 1 × 10(6), from adipose tissue (ATMSCs) were adhered to a Polyvicryl SF by adding a specific fibrin glue formulation. Adhesion was confirmed by confocal and scanning electron microscopy (SEM). A cecal fistula was created in 22 Wistar rats by incising the cecum and suturing the opening to the surgical wound subcutaneously with four separate stitches. The animals were randomly allocated to three groups: control (CG)-five animals, EF performed; injection (IG)-eight animals 1 × 10(6) ATMSCs injected around EF borders; and suture filament (SG): nine animals, sutured with 1 × 10(6) ATMSCs attached to the filaments with fibrin glue. Fistulas were photographed on the operation day and every 3 days until the 21st day and analyzed by two observers using ImageJ Software. RESULTS: Confocal and SEM results demonstrated ATMSCs adhered to SF (ATMSCs-SF). The average reduction size of the fistula area at 21st day was greater for the SG group (90.34%, P < 0.05) than the IG (71.80%) and CG (46.54%) groups. CONCLUSIONS: ATMSCs adhered to SF maintain viability and proliferative capacity. EF submitted to ATMSCs-SF procedure showed greater recovery and healing. This approach might be a new and effective tool for EF treatment.