Shape-defined solid micro-objects from poly(D,L-lactic acid) as cell-supportive counterparts in bottom-up tissue engineering

A.M. Leferink, M.P. Tibbe, E.G.B.M. Bossink, L.E. de Heus, H. van Vossen, A. van den Berg, L. Moroni, R.K. Truckenmüller*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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In bottom-up tissue engineering, small modular units of cells and biomaterials are assembled toward ​larger and more complex ones. In conjunction with a new implementation of this approach, a novel method to fabricate microscale objects from biopolymers by thermal imprinting on water-soluble sacrificial layers is presented. By this means, geometrically well-defined objects could be obtained without involving toxic agents in the form of photoinitiators. The micro-objects were used as cell-adhesive substrates and cell spacers in engineered tissues created by cell-guided assembly of the objects. Such constructs can be applied both for in vitro studies and clinical treatments. Clinically relevantly sized aggregates comprised of cells and micro-objects retained their viability up to 2 weeks of culture. The aggregation behavior of cells and objects showed to depend on the type and number of cells applied. To demonstrate the micro-objects’ potential for engineering vascularized tissues, small aggregates of human bone marrow stromal cells (hMSCs) and micro-objects were coated with a layer of human umbilical vein endothelial cells (HUVECs) and fused into larger tissue constructs, resulting in HUVEC-rich regions at the aggregates' interfaces. This three-dimensional network-type spatial cellular organization could foster the establishment of (premature) vascular structures as a vital prerequisite of, for example, bottom-up-engineered bone-like tissue.

Original languageEnglish
Article number100025
JournalMaterials Today Bio
Publication statusPublished - Sept 2019


  • Bone tissue engineering
  • Hot embossing/thermal imprinting
  • Human bone marrow stromal cells
  • Human umbilical vein endothelial cells
  • Poly(lactic acid)
  • Self-assembly

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