Poly( d , l lactic -co- glycolic) membranes seeded with human adipose stem cells for dermal substitute

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Poly(d,l lactic‑co‑glycolic) membranes seeded with human adipose stem cells for dermal substitute Adriana Cristina Motta1 · Moema Hausen1 · Talita Stessuk2 · Elaine Conceição de Oliveira3 · Anna Maria G. Melero4 · Eliana Aparecida de Rezende Duek1 Received: 21 March 2020 / Revised: 28 August 2020 / Accepted: 6 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Dermal substitutes must be flexible, degrade rapidly and stimulate the growth of new dermis preventing fibrosis formation. Bioreabsorbable polymers, such as poly (d,l lactic-co-glycolic) (PDLGA) do not stimulate tissue growth, but when associated with inductive molecules or cells, it can provide tissue repair. In this study, PDLGA (67:23) membranes were synthetized and to verify its degradation properties, it was analyzed before and after cell culture. Dynamic mechanical analysis showed that the copolymer presented force and deformation features desired as a dermal substitute. Early degradation after 7 days was shown by thermal and morphological analysis. The recent isolated adipose-derived mesenchymal stem cells, known to modulate scar and fibrosis formation, seeded in PDLGA membranes remained phenotypically undifferentiated. The fast degradation rate and the properties to support cell survival, directs to the PDLGA essential properties as a candidate for a polymer-cell construct, focused to modulate skin repair. Keywords  Adipose-derived stem cell · Dermal substitute · Poly(d,l lactic-coglycolic) · Skin tissue engineering

* Adriana Cristina Motta [email protected] 1

Biomaterials Laboratory, Pontifical Catholic University of São Paulo – PUC, Perdizes, SP, Brazil

2

Postgraduate Program in Biotechnology, University of São Paulo – USP, Butanta, SP, Brazil

3

Faculty of Technology of Sorocaba – FATEC, Sorocaba, SP, Brazil

4

REDEMAT, Federal University of Ouro Preto, Ouro Preto, MG, Brazil



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Polymer Bulletin

Introduction Several dermal substitutes have been developed for application in advanced wound healing; however, common problems involving its use are low flexibility, long degradation time, reduced vascularization, scarring and fibrosis, among others [1, 2] Poly(d,l lactic-co-glycolic) acid (PDLGA), a bioreabsorbable polymer, have been used in tissue engineering [3–5]. The major advantages of this polymer includes the biocompatibility, controlled degradation rate and is already approved for clinical use in humans by the US Food and Drug Administration (FDA) [6]. The degradation rate of this copolymer can be controlled changing the ratio between d,l- lactic acid and glycolic acid monomers since the d,l amount defines the amorphous regions proportion in the copolymer which is directly related to the degradation process due the great susceptibility to water molecules attack, and accelerate the PDLGA degradation process [7]. Dermal substitutes should degrade in a few months and be replaced by neodermis produced by the patients skin, as the tissue regenerates, the rate of material degrada