Autor(es)

Carvalho, Bruna Gregatti ; Nakayama, Aya ; Miwa, Hiromi ; Han, Sang Won ; de la Torre, Lucimara Gaziola ; Di Carlo, Dino ; Lee, Junmin ; Kim, Han-Jun ; Khademhosseini, Ali ; de Barros, Natan Roberto

• Tipo de documento: Artigo Científico
• Fonte: AGGREGATE; v. 5, n. 2, p. 15-pg., 2023-11-20.

Resumo

Messenger RNA (mRNA) therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra-articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease-mediated degradation and safe site-specific intracellular delivery. Herein, novel mRNA-releasing matrices based on RGD-moiety-rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds are reported. GelMA concentration in aerogel-based microgels (mu gels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10% GelMA mu gels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA-releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA-releasing biomaterials for tissue engineering. Discover a novel approach for localized messenger RNA (mRNA) delivery through gelatin methacryloyl microporous annealed particle scaffolds. The sustained release of mRNA complexes achieves indirect intracellular delivery. In contrast, direct intracellular delivery is achieved by cell adhesion on mRNA-releasing scaffolds. Witness a hybrid system achieving efficient protein expression, offering the potential for mRNA-releasing biomaterials for tissue engineering.image (AU)

• Processo FAPESP: 21/07057-4 - Hidrogéis microporosos formados por micropartículas (MAP) de gelatina metacrilada (GelMA) para entrega de vetores não virais
• Beneficiário: Bruna Gregatti de Carvalho
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 18/18523-3 - Síntese de micropartículas poliméricas via processo microfluídico de gotas para a liberação sustentada de vetores não virais aplicados em terapia gênica
• Beneficiário: Bruna Gregatti de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 21/11564-9 - Tecnologias emergentes para a síntese de nanoagregados lipídicos, novos materiais e modelos in vitro para monitoramento celular
• Beneficiário: Lucimara Gaziola de la Torre
• Modalidade de apoio: Auxílio à Pesquisa - Regular