Research Article: Low molecular weight ε-caprolactone-p-coumaric acid copolymers as potential biomaterials for skin regeneration applications

Date Published: April 8, 2019

Publisher: Public Library of Science

Author(s): Marco Contardi, Alejandro Alfaro-Pulido, Pasquale Picone, Susana Guzman-Puyol, Luca Goldoni, José J. Benítez, Antonio Heredia, Markus J. Barthel, Luca Ceseracciu, Giovanni Cusimano, Ornella Roberta Brancato, Marta Di Carlo, Athanassia Athanassiou, José A. Heredia-Guerrero, Tushar Jana.


ε-caprolactone-p-coumaric acid copolymers at different mole ratios (ε-caprolactone:p-coumaric acid 1:0, 10:1, 8:1, 6:1, 4:1, and 2:1) were synthesized by melt-polycondensation and using 4-dodecylbenzene sulfonic acid as catalyst. Chemical analysis by NMR and GPC showed that copolyesters were formed with decreasing molecular weight as p-coumaric acid content was increased. Physical characteristics, such as thermal and mechanical properties, as well as water uptake and water permeability, depended on the mole fraction of p-coumaric acid. The p-coumarate repetitive units increased the antioxidant capacity of the copolymers, showing antibacterial activity against the common pathogen Escherichia coli. In addition, all the synthesized copolyesters, except the one with the highest concentration of the phenolic acid, were cytocompatible and hemocompatible, thus becoming potentially useful for skin regeneration applications.

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Biodegradable, bioresorbable, and biocompatible polymers are becoming common materials for pharmaceutical uses, mainly in the design of novel medical devices such as implants, scaffolds, films, nanoparticles or nanofibers that can control the release of drugs and/or reproduce, mimic or replace some parts of the body [1–3]. Among these polymers, poly-ε-caprolactone (PCL), after a period of unpopularity respect to other resorbable polymers such as polylactides and polyglycolides [4], has regained much interest due to its excellent biocompatibility, easy and efficient synthesis, and low degradation rate in water [1, 5]. PCL is a petroleum-based polyester synthesized via high-yield lactone ring-opening polymerization (ROP) of ε-caprolactone (common name of the hexano-6-lactone) and whose final molecular weight can be strongly affected by choice of the catalyst used [6, 7]. Moreover, the molecular weight, usually between 3000 and 80000 g/mol, influences the degradation rate of PCL and can make it suitable for different applications [5, 8]. Thus, high molecular weight PCL is required for implants and scaffolds in order to maintain the stability of the material for months or years. For instance, Pitt and Schinder [9] demonstrated that PCL capsules (with a Mw ~66000 g/mol) remained intact after 2-years of implantation in rats.

The physicochemical properties of ε-caprolactone-p-coumaric acid copolymers can be tuned by controlling the relative proportions of both monomers. These molecules can polymerize by melt-polycondensation catalyzed by the sulfonic acid DBSA, originating thermoplastic free-standing polyester films. The molecular weight decreased with the PCA content, while the dispersity was reduced. These phenomena and the interaction between polymer chains, ruled by the aromatic and aliphatic nature of the repetitive units, influence the final characteristics of the copolymers. In general, melting points, enthalpies of fusion, and breathability were reduced as PCA content is raised. Meanwhile water uptake capacity was kept very low and plasticity was improved. All samples were bio- and hemocompatible except PCL/PCA 2:1. Moreover, the presence of PCA in the copolymers considerably increases the antioxidant properties and can partially inhibit the growth of E. coli. Considering the above results, the copolymer with mole ratio 4:1 can be considered as a suitable biomaterial for skin regeneration in wound management.




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