In the setting of tissue engineering and regenerative medicine, scaffolds with a specific 3-D architecture are often used to allow cellular infiltration. Cell infiltration can be accomplished in vitro prior to application of the biomaterial to the body (cell-seeded constructs) or in vivo after the scaffold has been applied to the body (acellular constructs). Especially in the latter case, cells should be stimulated to form the appropriate tissue. A relevant topic, therefore, is to study the development and evaluation of smart bioscaffolds containing instructive cues to direct cells to proliferate, migrate and differentiate, and eventually form tissues and organs.

Bio-scaffold2

The tissue engineering triade, making use of scaffold components (extracellar matrix, ECM), cells, and biomolecules

In the human body, the extracellular matrix provides the cells' microenvironment, so it is not surprising that matrix molecules (collagen, elastin and glycosaminoglycans) in combination with effector molecules (e.g. growth factors) are used to construct molecularly-defined scaffolds for tissue engineering and regenerative medicine. Next to the molecular composition of the scaffolds, the 3-D architecture is addressed. The general aim is to mimic the cells' microenvironment both biochemically and topologically, thus providing cells with the proper directions to create new tissues. A number of innovative technologies are applied, including, state-of-the-art lyophilisation, biomaterial arrays, and high-density gene expression microarrays. Target organs include skin, cartilage, blood vessels, diaphragm, and bladder/urethra. Projects within REFORM include:

  • Development of embryonic scaffolds recapitulating organogenesis in the adult environment
  • Development of a library of > 106 different bioscaffolds for high throughput selection of informative scaffolds\
  • Development of microscaffolds as injectable biomaterials
  • Development of controlled release systems of growth factors using biological capsules (lyophilisomes)
  • Evaluation of scaffolds in a clinical setting (skin regeneration in children and adults)
  • Development of scaffolds with specific spatial organisation (unidirectional, random-pored, radial)
  • Application of transcriptome analysis to evaluate biological processes in scaffolds in (pre)clinical models
  • Characterisation and generation of (stem) cell niches, e.g. using glycosaminoglycan (mimetics)

Bio-scaffold1

Collagen scaffold with pores that allow cellular infiltration

Dr. Toin van Kuppevelt, Department of Biochemistry