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 15μm widths by 100μm lengths, chosen to match heart stiffness and myocyte size. Successful encapsulation of native MGF peptide within microrods was achieved with delivery of MGF for 2weeks, 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 8h 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.