Publications (2)2.63 Total impact
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Article: Photocrosslinkable chitosan modified with angiopoietin-1 peptide, QHREDGS, promotes survival of neonatal rat heart cells.
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ABSTRACT: Myocardial infarction (MI) results in the death of cardiomyocytes (CM), which causes scar formation and pathological remodeling of the heart. The delivery of healthy myocytes or bone marrow cells reduces pathological remodeling after MI, however, current cell injection methods have low cell survival rates and high cell loss. The main objective of this work was to develop a novel hydrogel that can promote survival of CMs. Photocrosslinkable azidobenzoic acid modified chitosan (Az-chitosan) was conjugated with the angiopoietin-1-derived peptide, QHREDGS. This novel peptide is thought to mediate attachment and survival responses of CM to angiopoietin-1 via integrin binding. Thin layers of Az-chitosan, Az-chitosan-QHREDGS, and Az-chitosan-DGQESHR (scrambled peptide control) were spin coated on glass slides and photocrosslinked with application of UV light (365 nm). Neonatal rat heart cells cultured up to 5 days, demonstrated significantly higher attachment and viability on Az-chitosan-QHREDGS compared to cells on other hydrogel controls. Surfaces were also stained for the CM-specific marker troponin I, demonstrating significantly higher percentage of CMs on Az-chitosan-QHREDGS compared to Az-chitosan. The cells cultivated on Az-chitosan-QHREDGS demonstrated significantly lower levels of caspase 3/7 activation after taxol treatment in comparison to cells cultivated on the control hydrogels, glass substrate, or Az-chitosan linked to RGD, an established integrin binding peptide that did not protect against apoptosis. Thus, Az-chitosan-QHREDGS supports attachment and survival of neonatal rat heart cells.Journal of Biomedical Materials Research Part A 10/2010; 95(1):105-17. · 2.63 Impact Factor -
Article: Hydrogels modified with QHREDGS peptide support cardiomyocyte survival in vitro and after sub-cutaneous implantation
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ABSTRACT: Myocardial cell injection and tissue engineering could provide novel treatment options for heart diseases; however both approaches are limited by the loss of the transplanted myogenic cells. We hypothesized that novel hydrogels could promote cardiomyocyte survival and remedy this critical limitation. The hydrogel described here is based on a photocrosslinked form of chitosan, Az-chitosan, which was covalently bound to the QHREDGS peptide to promote cell survival. The QHREDGS amino acid sequence is thought to be the integrin binding site in angiopoietin-1, a growth factor which has cardioprotective properties. Covalent immobilization was performed using 1-ethyl-3-(-3-dimethylaminopropyl)carbodiimide chemistry. Elastic moduli of the Az-chitosan hydrogel were within the lower physiological range for the neonatal rat heart (1.9 AE 0.2 kPa for 10 mg/ml and 3.5 AE 0.6 kPa for 20 mg/ml). After 6 days of cultivation of neonatal rat heart cells encapsulated with the hydrogels, cell viability and elongation was significantly higher in the peptide modified groups compared to the Az-chitosan control. No significant differences were found in the ability of RGDS and QHREDGS hydrogels to support contractile function in vitro. After subcutaneous implantation of cardiomyocyte hydrogel-peptide constructs in Lewis rats for 7 days, both QHREDGS and RGDS similarly recruited endothelial cells. However, Az-chitosan-QHREDGS gel had a higher percentage of smooth muscle actin (SMA)-positive myofibroblasts. The QHREDGS peptide gel promoted cardiomyocyte elongation and assembly of contractile apparatus and reduced cardiomyocyte apoptosis significantly better than the RGDS peptide. The new Az-chitosan-QHREDGS hydrogel may markedly improve cardiac regeneration by cell therapy.
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2010
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University of Toronto
- Department of Chemical Engineering and Applied Chemistry
Toronto, Ontario, Canada
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