GelMA/bioactive silica nanocomposite bioinks for stem cell osteogenic differentiation

resumo

Leveraging 3D bioprinting for processing stem cell-laden biomaterials has unlocked a tremendous potential for fabricating living 3D constructs for bone tissue engineering. Even though several bioinks developed to date display suitable physicochemical properties for stem cell seeding and proliferation, they generally lack the nanosized minerals present in native bone bioarchitecture. To enable the bottom-up fabrication of biomimetic 3D constructs for bioinstructing stem cells pro-osteogenic differentiation, herein we developed multi-bioactive nanocomposite bioinks that combine the organic and inorganic building blocks of bone. For the organic component gelatin methacrylate (GelMA), a photocrosslinkable denaturated collagen derivative used for 3D bioprinting was selected due to its rheological properties display of cell adhesion moieties to which bone tissue precursors such as human bone marrow derived mesenchymal stem cells (hBM-MSCs) can attach to. The inorganic building block was formulated by incorporating mesoporous silica nanoparticles functionalized with calcium, phosphate and dexamethasone (MSNCaPDex), which previously proven to induce osteogenic differentiation. The newly formulated photocrosslinkable nanocomposite GelMA bioink incorporating MSNCaPDex nanoparticles and laden with hBM-MSCs was successfully processed into a 3D bioprintable construct with structural fidelity, and well dispersed nanoparticles throughout the hydrogel matrix. These nanocomposite constructs could induce the deposition of apatite in vitro, thus showing attractive bioactivity properties. Viability and differentiation studies showed that hBM-MSCs remained viable and exhibited osteogenic differentiation biomarkers when incorporated in GelMA/MSNCaPDex constructs and without requiring further biochemical, nor mechanical stimuli. Overall, our nanocomposite bioink has demonstrated excellent processability via extrusion bioprinting into osteogenic constructs with potential application in bone tissue repair and regeneration.

categoria

Engineering, Biomedical; Materials Science, Biomaterials

autores

Tavares, MT; Gaspar, VM; Monteiro, MV; Farinha, JPS; Baleizao, C; Mano, JF

Grupos

G5 - Materiais Biomiméticos, Biológicos e Vivos

Projectos

Bioengineered autonomous cell-biomaterials devices for generating humanised micro- tissues for regenerative medicine (ATLAS)

Desenvolvimento de hidrogeis de inspiracao marinha multifuncionais e de elevado desempenho para regeneracao de cartilagem, reticulados com ligacoes nao-covalentes e bio-instrutivas deslizantes. (MARGEL)

Produção de Plataformas Microcapsulares 3D+ para Avaliação Laboratorial em Larga Escala de Novas Terapias Combinatórias para o Cancro do Pâncreas (PANGEIA)

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2019)

agradecimentos

The authors would like to acknowledge the support of the European Research Council for project ATLAS, grant agreement ERC-2014-ADG-669858. This work was also supported by the Programa Operacional Competitividade e Internacionalizacao (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects Margel (PTDC/BTM-MAT/31498/2017). M. Tavares also thanks FCT for a PhD grant (FCT-PD/BD/114019/2015). The PANGEIA project PANGEIA (PTDC/BTM-SAL/30503/2017) is also acknowledged for the junior researcher contract of Vitor Gaspar. This work was also developed within the scope of the project CICECO-Aveiro Institute of Materials, FCT Ref. UID/CTM/50011/2019, financed by national funds through the FCT/MCTES. This work was also supported by Fundos Europeus Estruturais e de Investimento (FEEI), Programa Operacional Regional de Lisboa-FEDER (02/SAICT/2017), and national funds from Fundacao para a Ciencia e a Tecnologia (FCT-Portugal) and COMPETE (FEDER) within projects UIDB/00100/2020 (CQE), and PTDC/CTM-CTM/32444/2017 (02/SAICT/2017/032444).