Polypeptide or protein self-assembly has been applied to develop a variety of materials for biomedical applications. However, very little effort has been made to integrate nucleic acids as affinity ligands for molecular recognition into peptide-based material systems. The purpose of this work is to demonstrate that nucleic acid aptamers can be integrated into fibrin hydrogels as functional groups for binding bioactive growth factors. Fibrinogen was modified with bifunctional cross-linkers that were used to conjugate fibrinogen and aptamers via click chemistry. The results showed that chemical functionalization of fibrinogen with aptamers did not significantly change key parameters of fibrinogen self-assembly including gelation time, water content, and microstructure of the fibrin hydrogels. However, the apparent diffusivity of vascular endothelial growth factor (VEGF) was decreased in the presence of the anti-VEGF aptamer in the self-assembled fibrin hydrogel. As a result, the aptamer-functionalized fibrin hydrogel matrix could release VEGF in a sustained manner for more than 14 days while the native fibrin released the majority of VEGF within the first 4 days. The cell migration and tube formation assays showed that the released VEGF was bioactive. Moreover, sustained VEGF release could enhance endothelial cell and keratinocyte proliferation. The skin wound healing assay also indicated that the hybrid aptamer/fibrin hydrogel could promote the healing procedure. In conclusion, self-assembly of hybrid aptamer/protein conjugates may lead to the generation of new biomaterials for drug delivery and regenerative medicine.

Self-assembly of aptamer-functionalized fibrinogen for sustained growth factor delivery and enhanced skin wound healing

254th National Meeting (2017)

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