Arginine-Biofunctionalized Ternary Hydrogel Scaffolds of Carboxymethyl Cellulose–Chitosan–Polyvinyl Alcohol to Deliver Cell Therapy for Wound Healing
Alexandra A. P. Mansur,
Sandhra M. Carvalho,
Ramayana M. de M. Brito,
Nádia S. V. Capanema,
Isabela de B. Duval,
Marcelo E. Cardozo,
José B. R. Rihs,
Gabriela G. M. Lemos,
Letícia C. D. Lima,
Marina P. dos Reys,
Ana P. H. Rodrigues,
Luiz C. A. Oliveira,
Marcos Augusto de Sá,
Geovanni D. Cassali,
Lilian L. Bueno,
Ricardo T. Fujiwara,
Zelia I. P. Lobato,
Herman S. Mansur
Affiliations
Alexandra A. P. Mansur
Center of Nanoscience, Nanotechnology, and Innovation—CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, UFMG, Av. Presidente Antônio Carlos, 6627—Escola de Engenharia, Bloco 2—Sala 2233, Belo Horizonte 31270-901, MG, Brazil
Sandhra M. Carvalho
Center of Nanoscience, Nanotechnology, and Innovation—CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, UFMG, Av. Presidente Antônio Carlos, 6627—Escola de Engenharia, Bloco 2—Sala 2233, Belo Horizonte 31270-901, MG, Brazil
Ramayana M. de M. Brito
Laboratory of Immunobiology and Control of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Nádia S. V. Capanema
Center of Nanoscience, Nanotechnology, and Innovation—CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, UFMG, Av. Presidente Antônio Carlos, 6627—Escola de Engenharia, Bloco 2—Sala 2233, Belo Horizonte 31270-901, MG, Brazil
Isabela de B. Duval
Laboratory of Immunobiology and Control of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Marcelo E. Cardozo
Laboratory of Immunobiology and Control of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
José B. R. Rihs
Laboratory of Immunobiology and Control of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Gabriela G. M. Lemos
Center of Nanoscience, Nanotechnology, and Innovation—CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, UFMG, Av. Presidente Antônio Carlos, 6627—Escola de Engenharia, Bloco 2—Sala 2233, Belo Horizonte 31270-901, MG, Brazil
Letícia C. D. Lima
Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Marina P. dos Reys
Laboratory of Compared Pathology, Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Ana P. H. Rodrigues
Chemistry Department, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Luiz C. A. Oliveira
Chemistry Department, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Marcos Augusto de Sá
Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Geovanni D. Cassali
Laboratory of Compared Pathology, Department of Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Lilian L. Bueno
Laboratory of Immunobiology and Control of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Ricardo T. Fujiwara
Laboratory of Immunobiology and Control of Parasites, Department of Parasitology, Institute of Biological Sciences, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Zelia I. P. Lobato
Departamento de Medicina Veterinária Preventiva, Federal University of Minas Gerais, UFMG, Belo Horizonte 31270-901, MG, Brazil
Herman S. Mansur
Center of Nanoscience, Nanotechnology, and Innovation—CeNano2I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, UFMG, Av. Presidente Antônio Carlos, 6627—Escola de Engenharia, Bloco 2—Sala 2233, Belo Horizonte 31270-901, MG, Brazil
Wound healing is important for skin after deep injuries or burns, which can lead to hospitalization, long-term morbidity, and mortality. In this field, tissue-engineered skin substitutes have therapy potential to assist in the treatment of acute and chronic skin wounds, where many requirements are still unmet. Hence, in this study, a novel type of biocompatible ternary polymer hybrid hydrogel scaffold was designed and produced through an entirely eco-friendly aqueous process composed of carboxymethyl cellulose, chitosan, and polyvinyl alcohol and chemically cross-linked by citric acid, forming three-dimensional (3D) matrices, which were biofunctionalized with L-arginine (L-Arg) to enhance cellular adhesion. They were applied as bilayer skin biomimetic substitutes based on human-derived cell cultures of fibroblasts and keratinocytes were seeded and grown into their 3D porous structures, producing cell-based bio-responsive hybrid hydrogel scaffolds to assist the wound healing process. The results demonstrated that hydrophilic hybrid cross-linked networks were formed via esterification reactions with the 3D porous microarchitecture promoted by foam templating and freeze-drying. These hybrids presented chemical stability, physicochemical properties, high moisture adsorption capacity, surface properties, and a highly interconnected 3D porous structure well suited for use as a skin substitute in wound healing. Additionally, the surface biofunctionalization of these 3D hydrogel scaffolds with L-arginine through amide bonds had significantly enhanced cellular attachment and proliferation of fibroblast and keratinocyte cultures. Hence, the in vivo results using Hairless mouse models (an immunocompromised strain) confirmed that these responsive bio-hybrid hydrogel scaffolds possess hemocompatibility, bioadhesion, biocompatibility, adhesiveness, biodegradability, and non-inflammatory behavior and are capable of assisting the skin wound healing process.
