Geometrically Controlled Liquefied Capsules for Modular Tissue Engineering Strategies

abstract

A plethora of bioinspired cell-laden hydrogels are being explored as building blocks that once assembled are able to create complex and highly hierarchical structures recapitulating the heterogeneity of living tissues. Yet, the resulting 3D bioengineered systems still present key limitations, mainly related with limited diffusion of essential molecules for cell survival, which dictates the failure of most strategies upon implantation. To maximize the hierarchical complexity of bioengineered systems, while simultaneously fully addressing the exchange efficiency of biomolecules, the high-throughput fabrication of liquefied capsules is proposed using superhydrophobic-superhydrophilic microarrays as platforms to produce the initial structures with high fidelity of geometry and size. The liquefied capsules are composed by i) a permselective multilayered membrane; ii) surface-functionalized poly(epsilon-caprolactone) microparticles loaded into the liquefied core acting as cell adhesion sites; and iii) cells. It is demonstrated that besides the typical spherical liquefied capsules, it is also possible to obtain multi-shaped blocks with high geometrical precision and efficiency. Importantly, the internal gelation approach used to produce such blocks does not jeopardize cell viability, evidencing the mild conditions of the proposed cell encapsulation technique. The proposed system is intended to be used as hybrid devices implantable using minimally invasive procedures for multiple tissue engineering applications.

keywords

HYDROGELS; FABRICATION; CELLS

subject category

Materials Science

authors

Nadine, S; Patricio, SG; Barrias, CC; Choi, IS; Matsusaki, M; Correia, CR; Mano, JF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

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)

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

acknowledgements

The authors acknowledge the financial support given by the Portuguese Foundation for Science and Technology (FCT) with the doctoral grant of Sara Nadine (SFRH/BD/130194/2017), the projects 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). The authors also acknowledge funding from national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5, and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. This work was also partly supported by Japan Society for the Promotion of Science (JSPS) Bilateral Open Partnership Joint Research Projects. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement.