Liquefied Microcapsules Compartmentalizing Macrophages and Umbilical Cord-Derived Cells for Bone Tissue Engineering

resumo

Extraordinary capabilities underlie the potential use of immune cells, particularly macrophages, in bone tissue engineering. Indeed, the depletion of macrophages during bone repair often culminates in disease scenarios. Inspired by the native dynamics between immune and skeletal systems, this work proposes a straightforward in vitro method to bioengineer biomimetic bone niches using biological waste. For that, liquefied and semipermeable reservoirs generated by electrohydrodynamic atomization and layer-by-layer techniques are developed to coculture umbilical cord-derived human cells, namely monocyte-derived macrophages, mesenchymal-derived stromal cells (MSCs), and human umbilical vein endothelial cells (HUVECs). Poly(epsilon-caprolactone) microparticles are also added to the liquefied core to act as cell carriers. The fabricated microcapsules grant the successful development of viable microtissues, ensuring the high diffusion of bioactive factors. Interestingly, macrophages within the bioengineered microcapsules increase the release of osteocalcin, osteoprotegerin, and vascular endothelial growth factor. The cytokines profile variation indicates macrophages' polarization into a prohealing phenotype. Altogether, the incorporation of macrophages within the fabricated microcapsules allows to recreate an appropriate bone microenvironment for developing new bone mineralized microtissues. The proposed bioencapsulation protocol is a powerful self-regulated system, which might find great applicability in bone tissue engineering based on bottom-up approaches or disease modeling.

palavras-chave

MESENCHYMAL STEM-CELLS; OSTEOGENIC DIFFERENTIATION; ENDOTHELIAL-CELLS; HOST MACROPHAGES; LADEN HYDROGELS; IN-VITRO; IMMUNE; MINERALIZATION; ANGIOGENESIS; REGENERATION

categoria

Engineering; Science & Technology - Other Topics; Materials Science

autores

Nadine, S; Fernandes, I; Patricio, SG; Correia, CR; Mano, JF

Grupos

G5 - Materiais Biomiméticos, Biológicos e Vivos

Projectos

Regeneração Óssea Orquestrada pela Interação de Células do Sistema Imunitário com Microlaboratórios de Células e Microplataformas Padronizadas (CIRCUS)

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

Bioinspired tile-matching to create ultrastructured bone microtissues in a close-to-native fashion (TETRISSUE)

Desenvolvimento de uma membrana periodontal multicamada composta por blocos inovativos a base de polimeros de origem marinha e enzima para regeneracao guiada de osso que possui mineralizacao enzimatica controlada. (MIMETIc)

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

agradecimentos

S.N. acknowledges the financial support given by the Portuguese Foundation for Science and Technology (FCT) with the doctoral grant of Sara Nadine (SFRH/BD/130194/2017). This work was financed by national funds (OE) through FCT in the scope of the projects TETRISSUE (PTDC/BTM-MAT/3201/2020), CIRCUS (PTDC/BTM-MAT/31064/2017), and MIMETIc (PTDC/BTM-MAT/31210/2017) and the European Research Council for project ATLAS (ERC-2014-AdG-669858). CIRCUS and MIMETIc are also supported by the Programa Operacional Competitividade e InternacionalizacAo, in the component FEDER (POCI-01-0145-FEDER-031064 and POCI-01-0145-FEDER-031210). S.G.P. acknowledges the individual contract 2020.00366.CEECIND. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MCTES (PIDDAC).