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 inap...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(μgels)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%GelMAμgels 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.展开更多
基金National Institutes of Health,Grant/Award Numbers:HL140951,HL137193,CA257558,DK130566Ministry of Education,Grant/Award Number:RS-2023-00240729+3 种基金Korea University,Grant/Award Number:K2326671Coordenação de Aperfeiçoamento de Pessoal de Nível Superior,Grant/Award Numbers:2018/18523-3,2021/07057-4Fundação de AmparoàPesquisa do Estado de São Paulo,Grant/Award Numbers:2021/07057-4,2018/18523-3,2021/11564-9National Research Foundation of Korea,Grant/Award Number:RS-2023-00240729。
文摘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(μgels)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%GelMAμgels 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.
