Non-clinical safety study of a sugarcane bacterial cellulose hydrogel
Keywords:Bacterial Cellulose; Skin; Toxicity; Biopolymer
A hydrogel of bacterial cellulose of 0.8%, biopolymer produced from sugarcane molasses and synthesized from a bacteria called Zoogloea sp., was analyzed for its composition and tested by two routes of administration, subcutaneous and intraperitoneal, to clarify the local and systemic adverse effects after skin implantation in Wistar rats (24 males, 24 females, 55 days old). Analysis of two samples of BC films indicates carbon (42.94%; 43.43%), hydrogen (6.73%; 6.76%), nitrogen (0.28%, 0.23%) and oxygen (50.05%, 49.58%). No abnormal behavior, clinical signs of chronic toxicity or inflammation were observed. There was no change in liver injury biomarker levels (ALT, AST and ALP), as well as in renal histology, where it was evaluated to signs of tubular cell injury, glomerular or vascular damage, and renal morphometry, in which it was quantified the number of renal corpuscles, the number of cells per glomerulus and the capsular space area. Thus, the absence of signs and symptoms of toxicity suggests that subcutaneous or intraperitoneal injections of these polymers may be used in clinical situations.
Albuquerque, P. C. U. C., Santos, S. M., Aguiar, J. L. A., Filho, N. P., Mello, R. J. V., Costa, M. L. C. R., Olbertz, C. M. C. A., Almeida, T. M. S., Santos, A. H. S. & Silva, J. C. (2011) Comparative macroscopic study of osteochondral defects produced in femurs of rabbits repaired with biopolymer gel cane sugar. Revista Brasileira de Ortopedia, 46, 577–584.
Athukoralalage, S. S., Balu, R., Dutta, N. K. & Roy Choudhury, N. (2019) 3D Bioprinted nanocellulose-based hydrogels for tissue engineering applications: A Brief Review. Polymers, 11(5), 898-910.
Barros-Marques, S. R., Marques-Lins, E., Albuquerque, M. C. & Andrade-Aguiar, J. L. (2012) Sugarcane biopolymer patch in femoral vein angioplasty on dogs. Journal of Vascular Surgery, 55, 517–521.
Carvalho Junior, A. M., Barkokébas, B. B., Aguiar, J. L. A., Lima, S. V. C. & Dambros, M. (2012) Characterization of the deposition of collagen fibers and Lithogenic potential in bladder of rats submitted to a sugar cane biopolymer graft. International Brazilian Journal of Urology, 38, 544-551.
Castro, C. M. M. B., Aguiar, J. L. A., Melo, F. A., Silva, W. T. F., Marques, E., & Silva, D. B. (2004) Citotoxidade de Biopolímero de Cana-de-Açúcar. Anais da Faculdade de Medicina da Universidade Federal de Pernambuco, 49, 119-123.
Cavalcante, A., Lima, R. P., Souza, V., Pinto, F., Campos Júnior, O., Silva, J., Albuquerque, A. V., & Aguiar, J. (2018). Effects of bacterial cellulose gel on the anorectal resting pressures in rats submitted to anal sphincter injury. Heliyon, 4(12), e01058. https://doi.org/10.1016/j.heliyon.2018.e01058.
Cordeiro-Barbosa, F. A., Aguiar, J. L. A., Lira, M. M. M., Pontes Filho, N. T. & Bernadino-Araújo, S. (2012) Use of a gel biopolymer for the treatment of eviscerated eyes: experimental model in rabbits. Arquivos Brasileiros de Oftalmologia, 75(4), 267-272.
Curvello, R., Raghuwanshi, V. S. & Garnier, G. (2019) Engineering nanocellulose hydrogels for biomedical applications. Advances in Colloid and Interface Science, 267, 47-61.
Donini, I. A. N., Salvi, D.T. B., Fukumoto, F. K., Lustri, W. R., Barud, H. S., Marchetto, R., Messaddeq, Y. & Ribeiro, S. J. L. (2018) Biosynthesis and recent advances in production of bacterial cellulose. Eclética Química Journal, 35(4), 165-178.
Foresti, M. L., Vázquez, A. & Boury, B. (2017) Applications of bacterial cellulose as precursor of carbon and composites with metal oxide, metal sulfide and metal nanoparticles: A review of recent advances. Carbohydrate Polymers, 157, 447–467.
Fragoso, A. S., Silva, M. B., De Melo, C. P., Aguiar, J. L., Rodrigues, C. G., De Medeiros, P. L., Branco Junior, J. F., Andrade, C. A. S., & Oliveira, M. D. L. (2014) Dielectric study of the adhesion of mesenchymal stem cells from human umbilical cord on a sugarcane biopolymer. Journal of Materials Science: Materials in Medicine, 25, 229–237.
Gonçalves-Pimentel, C., Moreno, G. M. M., Trindade, B. S, Isaac A. R., Rodrigues, C. G., Savariradjane, M., Albuquerque, A. V., Aguiar, J. L. A., & Andrade-da-Costa, B. L. S. (2018) Cellulose exopolysaccharide from sugarcane molasses as a suitable substrate for 2D and 3D neuron and astrocyte primary cultures. Journal of Materials Science Materials in Medicine, 29(9), 139.
INTERNATIONAL ORGANIZATION FOR STANDARDIZATION. Available in https://www.iso.org/standard/68426.html: Access September 10, 2020.
Lima, S. V., de Oliveira Rangel, A. E., de Melo Lira, M. M., Pinto, F. C., Campos Júnior, O., Sampaio, F. J., & de Andrade Aguiar, J. L. (2015). The Biocompatibility of a Cellulose Exopolysaccharide Implant in the Rabbit Bladder When Compared With Dextranomer Microspheres Plus Hyaluronic Acid. Urology, 85(6), 1520.e1–1520.e15206.
Lima, S. V. C., Machado, M. R., Pinto, F. C. M, Lira, M. M. M., Albuquerque, A. V., Lustosa, E. S., Silva, J. G. M., & Campos Jr., O. (2017). A new material to prevent urethral damage after implantation of artificial devices: an experimental study. International braz j urol, 43(2), 335-344.
Lima, F. M., Pinto, F. C., Andrade-da-Costa, B. L., Silva, J. G., Campos Júnior, O., & Aguiar, J. L. (2017). Biocompatible bacterial cellulose membrane in dural defect repair of rat. Journal of materials science. Materials in medicine, 28(3), 37. https://doi.org/10.1007/s10856-016-5828-9
Lucena, R. G., Vilar, F. O., Andrade, R. T., Pinto, F. C. M. & Lima, S. V. C. (2015) Experimental use of a cellulosic biopolymer as a new material for suburethral sling in the treatment of stress urinary incontinence. International Braz J Urol (Online). 41:1148-1153.
Lucena, M. T., de Melo Júnior, M. R., de Melo Lira, M. M., de Castro, C. M., Cavalcanti, L. A., de Menezes, M. A., Pinto, F. C., & de Andrade Aguiar, J. L. (2015). Biocompatibility and cutaneous reactivity of cellulosic polysaccharide film in induced skin wounds in rats. Journal of materials science. Materials in medicine, 26(2), 82.
Martins, A. G. S., Lima, S. V. C., Araujo, L. A. P., Vilar, F. O. & Cavalcante, N. T. P. A. (2013) Wet dressing for hypospadias surgery. International Brazilian Journal of Urology, 39(3), 408-413.
OECD (2000). Guidance Document on the Recognition, Assessment and Use of Clinical Signs as Humane Endpoints. Organisation for Economic Co-operation and Development, Paris, France (OECD Series on Testing and Assessment, No. 19)
OECD (2002). Guidance Notes for Analysis and Evaluation of Chronic Toxicity and Carcinogenicity Studies. Organisation for Economic Co-operation and Development, Paris, 32 France (OECD Series on Testing and Assessment No. 35).
Oliveira, G. M., Vieira, J. M. S., Silva, J. G. M., Albuquerque, E. L. M. S., Albuquerque, A. V., Aguiar, J. L. A., & Pinto, F. C. M. (2019). Curativo de celulose bacteriana para o tratamento de lesões por pressão em pacientes hospitalizados. Revista Enfermagem Atual In Derme, 87(Edição Esp).
Pavia, D. L., Lampman, G. M., Kriz, G. & Vyvyan, J. (2010) Introdução à Espectroscopia, 4ª Edição, Cengage, 733p.
Picheth, G. F., Pirich, C. L., Sierakowski, M. R., Woehl, M. A., Sakakibara, C. N., de Souza, C. F., Martin, A. A., da Silva, R., & de Freitas, R. A. (2017). Bacterial cellulose in biomedical applications: A review. International journal of biological macromolecules, 104(Pt A), 97–106.
Pinto, F., De-Oliveira, A., De-Carvalho, R. R., Gomes-Carneiro, M. R., Coelho, D. R., Lima, S., Paumgartten, F., & Aguiar, J. (2016). Acute toxicity, cytotoxicity, genotoxicity and antigenotoxic effects of a cellulosic exopolysaccharide obtained from sugarcane molasses. Carbohydrate polymers, 137, 556–560.
Pita, P. C. C., Pinto, F. C. M., Lira, M. M. M., Melo, F. A. D., Ferreira, L. M. & Aguiar, J. (2015) Biocompatibility of the bacterial cellulose hydrogel in subcutaneous tissue of rabbits. Acta Cirúrgica Brasileira,. 30, 296-300.
Rangel, A. E. O., Aguiar, J. L. A., Lima, S. V. C. & Vilar F. (2006) A new biomaterial for the treatment of vesicoureteral reflux: Experimental study. International Brazilian Journal of Urology. 32, 184.
Reitman, S. & Frankel, S. (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28, 56-63.
Silveira, F. C. A., Pinto, F. C. M., Caldas Neto, S. S., Leal, M. C., Cesário, J. & Andrade, J. L. A. (2016) Treatment of tympanic membrane perforation using bacterial cellulose: a randomized controlled trial. Brazilian Journal of Otorhinolaryngology, 82(2), 203–208.
Silveira, R. K., Coelho, A. R., Pinto, F. C., de Albuquerque, A. V., de Melo Filho, D. A., & de Andrade Aguiar, J. L. (2016). Bioprosthetic mesh of bacterial cellulose for treatment of abdominal muscle aponeurotic defect in rat model. Journal of materials science. Materials in medicine, 27(8), 129.
How to Cite
Copyright (c) 2020 Jaiurte Gomes Martins da Silva; Flávia Cristina Morone Pinto; Glícia Maria de Oliveira; Anderson Arnaldo da Silva; Olávio Campos Júnior; Ricardo Oliveira da Silva; Valeria Wanderley Teixeira; Ismaela Maria Ferreira de Melo; Francisco José Roma Paumgartten; Thamyris Perez de Souza ; Rosangela Ribeiro de Carvalho; Ana Cecília Amado Xavier de Oliveira; José Lamartine de Andrade Aguiar; Álvaro Aguiar Coelho Teixeira
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.