Bioengineered Hierarchical Bonelike Compartmentalized Microconstructs Using Nanogrooved Microdiscs

abstract

Fabrication of vascularized large-scale constructs for regenerative medicine remains elusive since most strategies rely solely on cell self-organization or overly control cell positioning, failing to address nutrient diffusion limitations. We propose a modular and hierarchical tissue-engineering strategy to produce bonelike tissues carrying signals to promote prevascularization. In these 3D systems, disc-shaped microcarriers featuring nanogrooved topographical cues guide cell behavior by harnessing mechanotransduction mechanisms. A sequential seeding strategy of adipose-derived stromal cells and endothelial cells is implemented within compartmentalized, liquefied-core macrocapsules in a self-organizing and dynamic system. Importantly, our system autonomously promotes osteogenesis and construct's mineralization while promoting a favorable environment for prevascular-like endothelial organization. Given its modular and self-organizing nature, our strategy may be applied for the fabrication of larger constructs with a highly controlled starting point to be used for local regeneration upon implantation or as drug-screening platforms.

keywords

MESENCHYMAL STEM-CELLS; ENDOTHELIAL-CELLS; OSTEOGENIC DIFFERENTIATION; SURFACE-TOPOGRAPHY; MODULATION; COLLAGEN; MICROSPHERES; MEMBRANES; VESICLES; NETWORK

subject category

Science & Technology - Other Topics; Materials Science

authors

Bjorge, IM; de Sousa, BM; Patricio, SG; Silva, AS; Nogueira, LP; Santos, LF; Vieira, SI; Haugen, HJ; Correia, CR; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

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)

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

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)

3D cells colonization in marine-derived hydrogels through controlled micro-channels patterning for bone repair (PROMENADE)

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

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

acknowledgements

I.M.B., B.M.d.S., and L.F.S. acknowledge financial support by the Portuguese Foundation for Science and Technology (FCT) with doctoral grants SFRH/BD/129224/2017, 2020.06525.BD, and SFRH/BD/141523/2018, respectively. S.G.P. and A.S.S. acknowledge the individual contracts 2020.00366.CEECIND and 2020.04344.CEECIND, respectively. This work was supported by the European Research Council grant agreement for the project ATLAS (ERC-2014-ADG-669858). This work was financed by national funds (OE) through (FCT/MCTES) in the scope of the projects TETRISSUE, reference PTDC/BTM-MAT/3201/2020, CIRCUS, reference PTDC/BTM-MAT/31064/2017, MIMETIc, reference PTDC/BTM-MAT/31210/2017, and PROMENADE reference PTDC/BTM-MAT/29830/2017, supported, when applicable, by the Programa Operacional Competitividade e Internacionalizacao, in the component FEDER (POCI-01-0145-FEDER-031064 and POCI-01-0145-FEDER-031210). Mass spectrometry technique was performed at the Proteomics i3S Scientific Platform with the assistance of Hugo Osorio. This work had support from the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125). Image acquisition was performed in the LiM facility of iBiMED, a node of PPBI (Portuguese Platform of BioImaging): POCI-01-0145-FEDER-022122. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, and iBiMED (UID/BIM/04501/2019), financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement.