Leukopenia, weight loss and oral mucositis induced by 5-Fluorouracil in hamsters’ model: A regenerative approach using electrospun poly(Lactic-co-Glycolic Acid) membrane

TL;DR

This study explores how 5-Fluorouracil causes oral mucositis in hamsters and tests a new regenerative treatment using electrospun membranes.

Contribution

A novel regenerative approach using electrospun PLGA membranes with autologous cells for treating oral mucositis is proposed.

Findings

5-FU caused significant immunosuppression and weight loss in hamsters.

Electrospun PLGA membranes with autologous cells accelerated ulcerative lesion regeneration.

Cell-seeded membranes showed complete reepithelialization with minimal inflammation.

Abstract

Clinical parameters of leukogram and weight were analyzed in animal models before and after seven days of 5-FU infusions. A comparison of leukograms before and after 5-FU administrations was analyzed. The results showed a significative difference (p = 0,004), confirming the immunosuppression. There was a decrease in the weight of the animals after 7 days of 5-FU infusions (p = 0.02). After immunosuppression, oral mucositis (OM) ulcerative lesions were established. Two of ten animals were aleatory selected to receive PLGA dressings. The electrospun PLGA membranes with or without autologous cells were applied to the ulcerative lesions, aiming to accelerate the regeneration process. Although this therapeutic innovation for OM lesions was still not tested in the bioengineering area, morphological analysis presented promising results. Lesions covered by cell-free PLGA exhibited areas of inflammation persistence and angiogenesis, and cell-seeded PLGA membrane exhibited complete reepithelialization after 6 days, with minor inflammatory infiltrate. Interestingly, the present work showed preclinical parameters of cachexia induced by chemotherapy for cancer treatment. Moreover, it showed an innovative approach by applying dressings constituted of electrospun PLGA with the addition of autologous mesenchymal cells for OM ulcerative lesions. This promising innovation will pave the way for future applications in oral mucosa lesions.

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