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

Autor: Raquel Carvalhosa, Mikhail V. Tsurkan, Benedetta Bussolati, Carsten Werner, Giovanni Camussi, Peter Hauser, Andrea Zieris, Uwe Freudenberg
Rok vydání: 2012
Předmět:
Glycerol
Male
medicine.medical_specialty
medicine.medical_treatment
Basic fibroblast growth factor
Pharmaceutical Science
02 engineering and technology
Polyethylene Glycols
03 medical and health sciences
chemistry.chemical_compound
Mice
Regenerative medicine
Acute kidney injury
Renal therapy
In situ regeneration
Heparin hydrogel
Growth factor delivery
Epidermal growth factor
medicine
Animals
Regeneration
030304 developmental biology
Cell Proliferation
0303 health sciences
Kidney
Epidermal Growth Factor
Chemistry
Heparin
Regeneration (biology)
Growth factor
Hydrogels
Acute Kidney Injury
021001 nanoscience & nanotechnology
medicine.disease
3. Good health
Cell biology
Surgery
Mice
Inbred C57BL
medicine.anatomical_structure
Kidney Tubules
Self-healing hydrogels
Fibroblast Growth Factor 2
0210 nano-technology
medicine.drug
Zdroj: Journal of controlled release : official journal of the Controlled Release Society. 167(3)
ISSN: 1873-4995
Popis: 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.
Databáze: OpenAIRE
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