Delivery of human adipose stem cells spheroids into lockyballs

Karina R. Silva, Rodrigo A. Rezende, Frederico D.A.S. Pereira, Peter Gruber, Mellannie P. Stuart, Aleksandr Ovsianikov, Ken Brakke, Vladimir Kasyanov, Jorge V.L. Da Silva, José M. Granjeiro, Leandra S. Baptista, Vladimir Mironov

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Adipose stem cells (ASCs) spheroids show enhanced regenerative effects compared to single cells. Also, spheroids have been recently introduced as building blocks in directed selfassembly strategy. Recent efforts aim to improve long-term cell retention and integration by the use of microencapsulation delivery systems that can rapidly integrate in the implantation site. Interlockable solid synthetic microscaffolds, so called lockyballs, were recently designed with hooks and loops to enhance cell retention and integration at the implantation site as well as to support spheroids aggregation after transplantation. Here we present an efficient methodology for human ASCs spheroids biofabrication and lockyballs cellularization using micro-molded non-adhesive agarose hydrogel. Lockyballs were produced using two-photon polymerization with an estimated mechanical strength. The Young's modulus was calculated at level 0.1362 +/-0.009 MPa. Interlocking in vitro test demonstrates high level of loading induced interlockability of fabricated lockyballs. Diameter measurements and elongation coefficient calculation revealed that human ASCs spheroids biofabricated in resections of micro-molded non-adhesive hydrogel had a more regular size distribution and shape than spheroids biofabricated in hanging drops. Cellularization of lockyballs using human ASCs spheroids did not alter the level of cells viability (p > 0,999) and gene fold expression for SOX-9 and RUNX2 (p > 0,195). The biofabrication of ASCs spheroids into lockyballs represents an innovative strategy in regenerative medicine, which combines solid scaffold-based and directed self-assembly approaches, fostering opportunities for rapid in situ biofabrication of 3D building-blocks.

Original languageEnglish
Article numbere0166073
Number of pages14
JournalPLoS ONE
Issue number11
Publication statusPublished - 1 Nov 2016

Field of Science*

  • 2.6 Medical engineering
  • 3.1 Basic medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database


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