Wound-healing hydrogels synthetized by photopolymerization to improve skin tissue repair and disinfection

CAGNETTA, GONZALO; JOSEFA MARTUCCI; GALLASTEGUI, ANTONELA; LUIS IBARRA; MARTÍNEZ, SOL R.; PALACIOS, RODRIGO E.; CHESTA, CARLOS A.; GOMEZ MARIA LORENA

Simposio; XVII Simposio Latinoamericano de Polímeros (SLAP 2022); 2022

IntroductionAn ideal dressing to treat wound-healing shouldpresent some general properties such as: protectthe wound from the environment, possessappropriate hydrophilicity [1,2], biocompatibility,antimicrobial activity, proper adhesion andflexibility allowing mobility. One of the mostversatile materials to this end is the use ofdressings based on hydrogels. [3,4]We report here on the synthesis of hydrogels byphotopolymerization, with improved properties toaid wound healing and disinfection processes.These hydrogels have excellent swelling capacity,good mechanical stability, ductility, adhesivenessand temperature response properties. In biologicaltests, these new materials showed highbiocompatibility and antibacterial activity.ExperimentalWe synthetized three formulations ofhydrogels containing METAC/NIPAM named as:F1 (25 % NIPAM, 75% METAC), F2 (50% NIPAM,50% METAC) and F3 (75% METAC, 25% NIPAM).A silsesquioxano (SSO-1) was employed as acrosslinking agent and nanoparticles of poly(9,9-dioctylfluorene-alt-benzothiadiazole) as macro -photoinitiator [5]. Hydrogels were characterized byswelling capacity, DSC, FTIR, TGA, stress-strainand adhesiveness assays, etc. Biologicalproperties were carried-out in vitro thoughhemolysis, cellular viability and antibacterialactivity experiments.Results and DiscussionSwelling measurements were carried out in PBS(pH 7,4) at 25°C. Results are shown in Figure 1.0 20 40 60 80 10001020304050SWELLING (SW)TIME (h)F1F2F3Figure 1: Swelling degree from three formulations ofhydrogels in PBS 7.4 at 25°C.In all cases a high degree of swelling is observed,being higher for hydrogels with major content ofMETAC (ionic monomer).We carried out tensile test with the objective ofstudy the mechanical properties of the newmaterials. The formulations with higher content ofNIPAM monomer have Young?s modulus (E)comparable with those reported in bibliography[6,7]; E decreased with increasing ionic monomercomposition [8-10]. These results are particularlyimportant since suggest that hydrogels shouldmaintain their mechanical properties during thetime of healing.Biological studies were carried out to test thebiocompatibility and inherent antimicrobial activityof the synthesized materials. To this end, MTTexperiments were performed on eukaryotic cells toevaluate the biocompatibility of the new materials.These experiments were accomplished with theuse of human keratinocyte cultures (HaCaT) in thepresence of hydrogels and with the use of siliconediscs of similar dimensions to those of thepolymers experiments as controls wells.SILICONE F1 F2 F3020406080100120% CELL VIABILITYFigure 2: Percentage of cell viability measured by MTTassay from cell line HaCaT after 24 h of exposure withhydrogels.As shown in Figure 2 there is only a minordecrease in the cellular activity compared tocontrol experiments, which allows to affirm thathydrogels are biocompatible.Finally, to study the antibacterial activity wecompared the kinetics of S. aureus bacterialgrowth in presence and absence of hydrogels inculture medium. Results are shown in Figure 3.As shown below, F1 and F2 hydrogels cause aclear reduction in bacterial activity, so they can beclassified as bactericides, while the F3 formulationrevealed a bacteriostatic effect.0 1 2 3 4 5 60246810120 1 2 3 4 5 60246810LOG10UFC/mLTIME (h)CALDO CONTROLF1LOG10UFC/mLTIME (h)CALDO CONTROLF2F3Figure 3: Bacterial inhibition (S. aureus) kinetics for thethree formulations of hydrogels with its correspondingcontrols in black squares.These experiments suggest that our hydrogelscould aid in the healing process of wounds bykeeping the damaged area free of infection.In summary, the observed properties of thesynthesized hydrogels suggest that they could beemployed in the fabrication of biocompatiblematerials with applications in biomedicine, mainlyin wound-healing and disinfection.References1 Sweeney, I. R. Miraftab, M. Collyer. G. (2012)Int Wound J, 9:601.2 Yari, A. Yeganeh, H. Bakhshi, H. (2012) J MaterSci Mater Med, 23:2187.3 Boateng, S. (2008) J. Pharm Sci, 97:2892.4 Caló, E. Khutorynaskiy, V. (2015) Eor Polym J,65: 252.5 Gallastegui, A. (2020) Macromol. RapidCommun. 19006016 Omidian, H.P., (2010) Introduction to Hydrogels,Biomedical Applications of HydrogelsHandbook, R.M. Ottenbrite, Editor.SpringerScience+Business Media: New York,USA.7 Gatta, L. (2009). Journal of Biomedical MaterialsResearch Part A, 90A(1):292.8 Takigawa, T. (1997). Polym. Gels Networks 5(6):585.9 Haq, M.A. (2017) Materials Science andEngineering C 70 842.10 Muniz, E. C. Geuskens, G. (2001)Macromolecules 34:4480.