Aplicação de ferramentas de Engenharia de Tecidos na biofabricação de intestino delgado: desafios da Medicina Regenerativa
Data
2019-05-14
Autores
Carandina, Rafael Factor [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Artigo 1 Dos transplantes intestinais convencionais à Engenharia de Tecidos: estado da arte Resumo O intestino delgado é responsável pela realização de múltiplas funções, incluindo motilidade, digestão e absorção. Nos distúrbios gastrointestinais, algumas dessas funções são prejudicadas ou perdidas. A ressecção do segmento doente é uma abordagem comum. No entanto, os pacientes sofrem de complicações e de baixa qualidade de vida. Substituições funcionais são, portanto, necessárias para restaurar, reparar ou substituir partes danificadas do intestino. A Engenharia de Tecidos e a Medicina Regenerativa fornecem uma abordagem alternativa para reconstruir diferentes segmentos do trato gastrointestinal. Os desafios são grandes e a área é extremamente promissora. Artigo 2 Avaliação e caracterização de scaffolds de matriz extracelular para aplicações na Engenharia de Tecidos do trato gastrointestinal Resumo Várias estratégias têm sido exploradas para aumentar o número de enxertos de intestino delgado para transplantes e, principalmente, para diminuir as taxas de rejeição deste órgão transplantado. Avanços recentes na Medicina Regenerativa estão fornecendo novas abordagens para os estudos de reparação ou substituição funcional do intestino afetado, seja por traumas ou por doenças. Neste contexto, a Engenharia de Tecidos pode ser uma opção para produzir scaffolds biocompatíveis para a produção de segmentos de intestino delgado em laboratório. Desta forma, o objetivo deste estudo foi avaliar e caracterizar diferentes protocolos de descelularização de intestino delgado de ratos Wistar para a produção de scaffolds tubulares. Nossos resultados mostraram que a criopreservação dos intestinos a -80℃, seguida de imersão e agitação moderada em Deoxicolato de Sódio (DS) a 1% durante 2 horas foi o protocolo mais efetivo na remoção nas células e melhor preservação da matriz extracelular, além de preservar a resistência mecânica. Porém, estudos adicionais de otimização do processo de descelularização devem ser implementados para garantir um maior controle de qualidade e produção em escala desses scaffolds, já que os mesmos apresentaram fragmentos longos de DNA residual, os quais podem ser um potencial agente imunogênico.
From conventional intestinal transplants to Tissue Engineering: state of the art ABSTRACT The small intestine is responsible for performing multiple functions including motility, digestion and absorption of food and nutrients. In gastrointestinal disorders, some of these functions are impaired or lost. Resection of the diseased segment is a common approach; however, patients suffer from complications and poor quality of life. Functional replacements are therefore necessary to restore, repair or replace damaged parts of the gut. Tissue Engineering and Regenerative Medicine provide an alternative approach to reconstruct different segments of the gastrointestinal tract. There are many challenges and the research field is extremely promising. Evaluation and characterization of extracellular matrix scaffolds for applications in Tissue Engineering of the gastrointestinal tract ABSTRACT Several strategies have been explored to increase the number of small bowel grafts intended for transplants and, mainly, to decrease the rejection rates of this transplanted tissue. Recent advances in Regenerative Medicine are providing new approaches for studies of functional repair or replacement of the affected bowel, whether by trauma or disease. In this context, Tissue Engineering has become an option to produce biocompatible scaffolds in order to produce segments of the small intestine in the laboratory, mainly through the application of ex-vivo tissue decellularization methodologies. Thus, the objective of this study was to evaluate and characterize different protocols of small intestinal decellularization of Wistar rats to produce tubular scaffolds. Our results showed that intestinal cryopreservation at -80 ℃, followed by immersion and moderate agitation in 1% Sodium Deoxycholate (SD) for 2 hours was the most effective protocol for removal of cells and better preservation of the extracellular matrix, besides mechanical strength. However, further studies of optimization of the decellularization process should be implemented to ensure a higher quality control and scale production of these scaffolds, since they have long fragments of residual DNA, which may be a potential immunogenic agent.
From conventional intestinal transplants to Tissue Engineering: state of the art ABSTRACT The small intestine is responsible for performing multiple functions including motility, digestion and absorption of food and nutrients. In gastrointestinal disorders, some of these functions are impaired or lost. Resection of the diseased segment is a common approach; however, patients suffer from complications and poor quality of life. Functional replacements are therefore necessary to restore, repair or replace damaged parts of the gut. Tissue Engineering and Regenerative Medicine provide an alternative approach to reconstruct different segments of the gastrointestinal tract. There are many challenges and the research field is extremely promising. Evaluation and characterization of extracellular matrix scaffolds for applications in Tissue Engineering of the gastrointestinal tract ABSTRACT Several strategies have been explored to increase the number of small bowel grafts intended for transplants and, mainly, to decrease the rejection rates of this transplanted tissue. Recent advances in Regenerative Medicine are providing new approaches for studies of functional repair or replacement of the affected bowel, whether by trauma or disease. In this context, Tissue Engineering has become an option to produce biocompatible scaffolds in order to produce segments of the small intestine in the laboratory, mainly through the application of ex-vivo tissue decellularization methodologies. Thus, the objective of this study was to evaluate and characterize different protocols of small intestinal decellularization of Wistar rats to produce tubular scaffolds. Our results showed that intestinal cryopreservation at -80 ℃, followed by immersion and moderate agitation in 1% Sodium Deoxycholate (SD) for 2 hours was the most effective protocol for removal of cells and better preservation of the extracellular matrix, besides mechanical strength. However, further studies of optimization of the decellularization process should be implemented to ensure a higher quality control and scale production of these scaffolds, since they have long fragments of residual DNA, which may be a potential immunogenic agent.
Descrição
Palavras-chave
Medicina Regenerativa, Engenharia de Tecidos, Intestino delgado, Scaffold, Transplante