title: Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes.
abstract: Local release of drugs may have many advantages for tissue repair but also presents major challenges. Bioengineering approaches allow microstructures to be fabricated that contain bioactive peptides for sustained local delivery. Heart tissue damage is associated with local increases in mechano growth factor (MGF), a member of the IGF-1 family. The E domain of MGF peptide is anti-apoptotic and a stem cell homing factor. The objectives of this study were to fabricate a microrod delivery device of poly (ethylene glycol) dimethacrylate (PEGDMA) hydrogel loaded with MGF peptide and to determine the elution profile and bioactivity of MGF. The injectable microrods are 30 kPa stiffness and 15 μm widths by 100 μm lengths, chosen to match heart stiffness and myocyte size. Successful encapsulation of native MGF peptide within microrods was achieved with delivery of MGF for 2 weeks, as measured by HPLC. Migration of human mesenchymal stem cells (hMSCs) increased with MGF microrod treatment (1.72 ± 0.23, p < 0.05). Inhibition of the apoptotic pathway in neonatal rat ventricular myocytes was induced by 8 h of hypoxia (1 % O2). Protection from apoptosis by MGF microrod treatment was shown by the TUNEL assay and increased Bcl-2 expression (2 ± 0.19, p < 0.05). Microrods without MGF regulated the cytoskeleton, adhesion, and proliferation of hMSCs, and MGF had no effect on these properties. Therefore, the combination microdevice provided both the mechanical cues and 2-week MGF bioactivity to reduce apoptosis and recruit stem cells, suggesting potential use of MGF microrods for cardiac regeneration therapy in vivo.
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Golnar
authors.initials: G
authors.lastname: Doroudian
authors.forename: James
authors.initials: J
authors.lastname: Pinney
authors.forename: Perla
authors.initials: P
authors.lastname: Ayala
authors.forename: Tamara
authors.initials: T
authors.lastname: Los
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
authors.forename: Brenda
authors.initials: B
authors.lastname: Russell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008689:Methacrylates; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D011092:Polyethylene Glycols; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000595707:BCL2 protein, human; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008689:Methacrylates; D019253:Proto-Oncogene Proteins c-bcl-2; C523997:mechano-growth factor E, human; C421283:poly(ethylene glycol)-dimethacrylate; D011092:Polyethylene Glycols; D007334:Insulin-Like Growth Factor I