Combined use of novel chitosan-grafted N-hydroxyethyl acrylamide polyurethane and human dermal fibroblasts as a construct for in vitro-engineered skin

• Published in: International journal of biological macromolecules 2023-05, Vol.238, p.124136-124136, Article 124136
• Main Authors: González-Torres, Maykel, Elizalde-Cárdenas, Alejandro, Leyva-Gómez, Gerardo, González-Mendoza, Oswaldo, Lima, Enrique, Núñez-Tapia, Israel, Abad-Contreras, David Eduardo, Luisa Del Prado-Audelo, María, Pichardo-Bahena, Raúl, Carlos-Martínez, Alberto, Ribas-Aparicio, Rosa María
• Format: Article
• Language: English
• Subjects: Acrylamide; Biopolymers; Chitosan; Chitosan - chemistry; Fibroblast; Fibroblasts; Humans; N-hydroxyethyl acrylamide; Polymer synthesis; Polyurethanes - chemistry; Skin
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.124136

A rich plethora of information about grafted chitosan (CS) for medical use has been reported. The capability of CS-grafted poly(N-hydroxyethyl acrylamide) (CS-g-PHEAA) to support human dermal fibroblasts (HDFs) in vitro has been proven. However, CS-grafted copolymers lack good stiffness and the characteristic microstructure of a cellular matrix. In addition, whether CS-g-PHEAA can be used to prepare a scaffold with a suitable morphology and mechanical properties for skin tissue engineering (STE) is unclear. This study aimed to show for the first time that step-growth polymerizations can be used to obtain polyurethane (PU) platforms of CS-g-PHEAA, which can also have enhanced microhardness and be suitable for in vitro cell culture. The PU prepolymers were prepared from grafted CS, polyethylene glycol, and 1,6-hexamethylene diisocyanate. The results proved that a poly(saccharide-urethane) [(CS-g-PHEAA)-PU] could be successfully synthesized with a more suitable microarchitecture, thermal properties, and topology than CS-PU for the dynamic culturing of fibroblasts. Cytotoxicity, proliferation, histological and immunophenotype assessments revealed significantly higher biocompatibility and cell proliferation of the derivative concerning the controls. Cells cultured on (CS-g-PHEAA)-PU displayed a quiescent state compared to those cultured on CS-PU, which showed an activated phenotype. These findings may be critical factors in future studies establishing wound dressing models. [Display omitted] •CS and (CS-graft N-hydroxyethyl acrylamide) polyurethanes were synthesized.•The polyurethane scaffoldings were obtained by step-growth polymerization.•Microarchitecture and topology were enhanced for grafted-CS polyurethane.•The (CS-g-PHEAA)-PU revealed significantly higher biocompatibility than CS-PU.•The (CS-g-PHEAA)-PU mimicked artificial skin tissue better than CS-PU scaffolds.