期刊
ADVANCED HEALTHCARE MATERIALS
卷 11, 期 20, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202200651
关键词
biomimetic bone niches; dynamic cultures; electrohydrodynamic atomization; liquefied microcapsules; macrophages; osteoimmunomodulation; umbilical cord-derived cells
资金
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/130194/2017]
- FCT [PTDC/BTM-MAT/3201/2020, PTDC/BTM-MAT/31064/2017, PTDC/BTM-MAT/31210/2017]
- European Research Council [ERC-2014-AdG-669858]
- Programa Operacional Competitividade e Internacionalizacao, FEDER [POCI-01-0145-FEDER-031064, POCI-01-0145-FEDER-031210]
- FCT/MCTES (PIDDAC) [UIDB/50011/2020, UIDP/50011/2020, LA/P/0006/2020]
- [2020.00366.CEECIND]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/130194/2017] Funding Source: FCT
This study proposes a method to bioengineer biomimetic bone niches using immune cells, particularly macrophages. The incorporation of macrophages within the fabricated microcapsules allows for the recreation of an appropriate bone microenvironment and the development of new bone mineralized microtissues. The findings indicate the potential of using this method in bone tissue engineering and disease modeling.
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.
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