Growth factor delivery from hydrogel particle aggregates to promote tubular regeneration after acute kidney injury

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Mikhail V. Tsurkan - , Center for Regenerative Therapies Dresden, Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, VA Medical Center, University of California at Los Angeles (Author)
  • Peter V. Hauser - , University of Turin (Author)
  • Andrea Zieris - , Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, TUD Dresden University of Technology (Author)
  • Raquel Carvalhosa - , University of Turin (Author)
  • Benedetta Bussolati - , University of Turin (Author)
  • Uwe Freudenberg - , Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, TUD Dresden University of Technology (Author)
  • Giovanni Camussi - , University of Turin (Author)
  • Carsten Werner - , Center for Regenerative Therapies Dresden, Chair of Biofunctional Polymer Materials, Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden (Author)

Abstract

Local delivery of growth factors (GFs) can accelerate regeneration of injured tissue, but for many medical applications, injectable GF delivery systems are required for clinical success. Viscoelastic, injectable aggregates of micrometer-sized hydrogel particles made of multiarmed polyethylene glycol (starPEG) and heparin were prepared and tested for site-specific paracrine stimulation of tissue regeneration. Heparin was used as it binds, protects and releases numerous GFs. Hydrogel based delivery of basic fibroblast growth factor (bFGF) and murine epidermal growth factor (EGF) was monitored utilizing enzyme-linked immunosorbent assay (ELISA). bFGF was released slowly because of its high affinity to the heparin while the significantly higher release of the non-specific binding EGF was controlled by diffusion only. To investigate GF delivery in vivo, a hydrogel loaded with murine EGF or bFGF was injected subcapsularly into the left kidney of mice with experimental acute kidney injury caused by glycerol induced rhabdomyolysis. Visual examination confirmed sustained stability of the injected gel aggregates during the timescale of the experiment. The number of proliferating kidney tubular epithelial cells was quantified both in the injected kidney and the non-injected contralateral kidney. bFGF delivery from hydrogels induced a significant increase in cell proliferation in the injected kidney, although small effects were also seen in the non-injected kidney due to a systemic effect. EGF delivery strongly increased cell proliferation for both kidneys, but also showed a local effect on the injected kidney. The hydrogel without loaded GFs was used as a control and showed no increase in cell proliferation. Our results suggest that this novel starPEG-heparin hydrogel system can be an effective approach to deliver GFs locally.

Details

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalJournal of controlled release
Volume167
Issue number3
Publication statusPublished - 10 May 2013
Peer-reviewedYes

External IDs

PubMed 23395667
ORCID /0000-0003-0189-3448/work/161890490

Keywords

ASJC Scopus subject areas

Keywords

  • Acute kidney injury, Growth factor delivery, Heparin hydrogel, In situ regeneration, Regenerative medicine, Renal therapy