A Synergic Strategy: Adipose-Derived Stem Cell Spheroids Seeded on 3D-Printed PLA/CHA Scaffolds Implanted in a Bone Critical-Size Defect Model

Author:

Kronemberger Gabriela S.123,Palhares Thiago Nunes4ORCID,Rossi Alexandre Malta4,Verçosa Brunno R. F.1,Sartoretto Suelen C.5ORCID,Resende Rodrigo5,Uzeda Marcelo J.5ORCID,Alves Adriana T. N. N.5,Alves Gutemberg G.5ORCID,Calasans-Maia Mônica D.5ORCID,Granjeiro José Mauro235ORCID,Baptista Leandra Santos123ORCID

Affiliation:

1. Nucleus of Multidisciplinary Research in Biology (Numpex-Bio), Federal University of Rio de Janeiro (UFRJ) Xerém, Duque de Caxias 25245-390, RJ, Brazil

2. Laboratory of Eukariotic Cells, National Institute of Metrology, Quality and Technology (Inmetro), Duque de Caxias 25250-020, RJ, Brazil

3. Post-Graduation Program of Translational Biomedicine (Biotrans), Unigranrio, Campus I, Duque de Caxias 25071-202, RJ, Brazil

4. Brazilian Center for Physics Research, Xavier Sigaud 150, Urca 22290-180, RJ, Brazil

5. Laboratory of Clinical Research in Odontology, Fluminense Federal University (UFF), Niterói 24020-140, RJ, Brazil

Abstract

Bone critical-size defects and non-union fractures have no intrinsic capacity for self-healing. In this context, the emergence of bone engineering has allowed the development of functional alternatives. The aim of this study was to evaluate the capacity of ASC spheroids in bone regeneration using a synergic strategy with 3D-printed scaffolds made from poly (lactic acid) (PLA) and nanostructured hydroxyapatite doped with carbonate ions (CHA) in a rat model of cranial critical-size defect. In summary, a set of results suggests that ASC spheroidal constructs promoted bone regeneration. In vitro results showed that ASC spheroids were able to spread and interact with the 3D-printed scaffold, synthesizing crucial growth factors and cytokines for bone regeneration, such as VEGF. Histological results after 3 and 6 months of implantation showed the formation of new bone tissue in the PLA/CHA scaffolds that were seeded with ASC spheroids. In conclusion, the presence of ASC spheroids in the PLA/CHA 3D-printed scaffolds seems to successfully promote bone formation, which can be crucial for a significant clinical improvement in critical bone defect regeneration.

Funder

National Council for Scientific and Technological Development

Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro

Office of Naval Research

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil

National Centre of Science and Technology on Regenerative Medicine

Publisher

MDPI AG

Subject

Biomedical Engineering,Biomaterials

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