Growth of epithelial cells on films of enzymatically synthesized poly(gallic acid) crosslinked to carboxymethylcellulose† Alejandra Romero-Montero, a Alberto Tecante, a Roeb Garc ´ ıa-Arrazola, a Carmina Montiel, a Luis J. del Valle, b Jordi Puiggal ´ ı b and Miquel Gimeno * a Poly(gallic acid), a novel polymer obtained by enzymatic polymerization of gallic acid, was successfully cross-linked to carboxymethylcellulose using citric acid as a cross-linker. Non-woven sheets were prepared with the resulting copolymer and their in vitro biocompatibility was assessed. The results on the characterizations of the produced films by mechanical tests, water vapour permeability, contact angle, and antioxidant activity by electronic paramagnetic resonance were adequate for skin tissue regeneration. Films were also decomposed under physiological conditions using universal buffers at pH 3, 7 and 10. In vitro experiments with fibroblast-like and epithelial-like cells showed good adhesion and proliferation onto the PGAL-co-CMC sheets. These non-woven sheets can consequently be considered as novel biocompatible and biodegradable films with high-responsiveness for biomedical or tissue engineering applications. Introduction The biomaterials composed of polymers from natural sources found applications in tissue engineering owing to their good biocompatibility, superior responses, few side effects and reduction or even suppression of secondary treatments or surgeries. 1–5 Additionally, they are also studied in neurology, medical imaging, bionic medicine, biomechanics or bio-nano- technology. 6 Generally, the improvement of the properties of these biomaterials to meet the requirements for specic biomedical application includes adequate mechanical proper- ties, stability in aqueous environments, vapour barrier proper- ties and cell biocompatibility, all these concomitantly with synthetic reproducibility in the absence of toxic processes and reagents. 6,7 In this regard, the use of non-toxic carboxylic acids as cross-linking agents between two or more polymer back- bones, such as citric acid (CA), proved successful to render tissue engineering materials with superior biocompatibility compared to those derived from other cytotoxic crosslinkers, such as glutaraldehyde or formaldehyde. 8 Among the studied polymers matrices, the approaches using the naturally abun- dant cellulose and its derivatives are encouraging owing to their low costs and availability in addition to good biocompatibility. Specically, the water-soluble carboxymethyl celluloses (CMC)s have multiple biomedical uses such as in heart, chest and cornea surgeries in addition to orthopaedic and pharmaceutical applications, among others. 9,10 On the other hand, plant polyphenols have attracted wide interest in the biomedical eld especially due to their radical scavenging activities (RSA) and antimicrobial capacities. Free radical species promote interaction within cells leading to proteins, membrane and gene damage and additionally, the oxidative stresses generated by the so-called radical oxygen species (ROS) are involved not only in wound healing processes but also in other several metabolic syndromes and inamma- tory processes. 11–13 Thus, the preparation of matrices with antioxidant activity to protect cells and tissues from oxidative damage has been achieved by incorporation of oxidant radical scavenger molecules, e.g. water-soluble forms of vitamin B6 (pyridoxine, pyridoxal and pyridoxamine), and small poly- phenols such as coumaric and caffeic acids. 14,15 Nonetheless, the characteristics in most of the natural polyphenol extracts, specially their low molecular stability against temperature or UV-irradiation, as well as high hydrophobicity or their limited extractions in large quantities restricts their bioavailability and processability; thereby their modications play an important role to produce synthetic derivatives with adequate character- istics and scale-up feasibility. 16 Enzyme-mediated modications offer environmentally favourable and mild process conditions that resulted in non-toxic products. 17,18 Glycosylation or esteri- cation of plant antioxidants proved to be successful for these purposes. 19,20 Additionally, the oxidative polymerization of a Facultad de Qu´ ımica, Departamento de Alimentos y Biotecnolog´ ıa, Universidad Nacional Aut´ onoma de M´ exico, Ciudad Universitaria, Ciudad de M´ exico, Mexico. E-mail: mgimeno@unam.mx b Chemical Engineering Department, Escola d'Enginyeria de Barcelona Est-EEBE, c/ Eduard Maristany 10-14, Barcelona, Spain † Electronic supplementary information (ESI) available. See DOI: 10.1039/c7ra00883j Cite this: RSC Adv. , 2017, 7, 17660 Received 20th January 2017 Accepted 16th March 2017 DOI: 10.1039/c7ra00883j rsc.li/rsc-advances 17660 | RSC Adv. , 2017, 7, 17660–17669 This journal is © The Royal Society of Chemistry 2017 RSC Advances PAPER Open Access Article. Published on 22 March 2017. Downloaded on 9/29/2021 8:08:55 PM. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online View Journal | View Issue