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

Bruna Maria Manzini; José Luis Dávila; Bruno Bosch Volpe; Adriana da Silva Santos Duarte; Maria Teresa Ferreira Côrtez; Eliana Aparecida de Rezende Duek; Wagner José Fávaro; Marcos Akira d'Ávila; Ricardo Kalaf Mussi; Ângela Cristina Malheiros Luzo

doi:10.1016/j.jss.2022.03.024

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

J Surg Res. 2022 Sep:277:319-334. doi: 10.1016/j.jss.2022.03.024. Epub 2022 May 9.

Affiliations

¹ Stem Cell Processing Laboratory, Hematology Hemotherapy Center, University of Campinas, Campinas, Brazil; Laboratory of Three-Dimensional Technologies, Center for Information Technology Renato Archer (CTI), Campinas, Brazil. Electronic address: brunamanzini@gmail.com.
² Laboratory of Three-Dimensional Technologies, Center for Information Technology Renato Archer (CTI), Campinas, Brazil; Department of Manufacturing and Materials Engineering, School of Mechanical Engineering, University of Campinas, Campinas, Brazil.
³ Stem Cell Processing Laboratory, Hematology Hemotherapy Center, University of Campinas, Campinas, Brazil.
⁴ Faculty of Medical Sciences, Pontifical Catholic University of São Paulo, Sorocaba, Brazil.
⁵ Structural and Functional Biology Department, Institute of Biology, University of Campinas, Campinas, Brazil.
⁶ Department of Manufacturing and Materials Engineering, School of Mechanical Engineering, University of Campinas, Campinas, Brazil.
⁷ Thoracic Surgery Department, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.

PMID: 35552075
DOI: 10.1016/j.jss.2022.03.024

Abstract

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.

Keywords: Biomaterials; Mesenchymal stem cells; Tissue engineering; Trachea.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cells, Cultured
Collagen Type I
Fistula*
Lactic Acid
Matrix Metalloproteinases
Polyesters
Swine
Tissue Engineering / methods
Tissue Scaffolds*
Vascular Endothelial Growth Factor A

Substances

Collagen Type I
Polyesters
Vascular Endothelial Growth Factor A
Lactic Acid
Matrix Metalloproteinases