ESR 2: Identification and application of specific elastin hydrolysates for scarless skin regeneration – The Netherlands

Host institution: Radboud university medical center (Radboudumc), The Netherlands


Supervisors:

  • Main supervisor: Dr. Willeke Daamen (Radboudumc, Radboud Institute for Molecular Life Sciences, Department of Biochemistry)
  • Co-supervisor: Dr. Toin van Kuppevelt (Radboudumc, Radboud Institute for Molecular Life Sciences, Department of Biochemistry)

Enrolment PhD training program: Radboudumc


Planned secondments:

Brief description:

Elastin is a largely neglected extracellular matrix protein, even though its biological and biomechanical elastin characteristics make it an attractive protein to develop biomaterials for scarless skin regeneration. Effective elastin preparations are crude fractions derived from mature elastic fibres that induce skin regeneration without scarring and wound contraction. In this project, fractionated elastin preparations are studied. Availability of such preparations may lead to improved (commercial) skin substitutes for wound healing and to more powerful agents for scarless healing.


The project is divided into three specific objectives:

  • Preparation and characterisation of defined elastin hydrolysates. Elastin will be purified from ligamentum nuchae. Soluble elastin preparations will be made by treatment with oxalic acid (α-elastin), KOH (κ-elastin), and elastase, followed by fractionation by a number of chromatographical methods, after which fractions will be analysed biochemically.
  • In vitro evaluation of fractionated elastin hydrolysates. Fractionated elastin hydrolysates will be analysed for their capacity to prevent differentiation of primary fibroblasts into myofibroblasts (cooperation VUMC; high content microscopy, immunofluorescence) and for their capacity to induce a M2 phenotype (cooperation UZH using specific markers). Promising elastin fractions are analysed (mass spectrometry; cooperation HMGU), characterised for the type/abundance of crosslinks (HPLC), and evaluated for the signalling pathway they activate.
  • In vivo analysis of scaffolds containing fractionated elastin hydrolysates for scarless skin regeneration. Scaffolds will be constructed from the two most promising elastin hydrolysate fractions which are evaluated in a rat model for full-thickness skin defects, and evaluated for scarless skin regeneration without wound contraction by macroscopic analysis, qPCR, and (immune)histochemistry.

Project specific requirements:

  • MSc in Life Science/(Bio)chemistry/Biomedical sciences/Biology or similar
  • Expertise in the following areas is highly recommendable: general protein biochemistry,  chromatographical methods like ion-exchange, gel filtration and hydrophobic interaction chromatography (FPLC), cell culture, (immune)histology, and animal research
  • Permission to work with animals (art. 9) is a benefit

Please apply before December 21, 2020 via this APPLY link.