Controlled delivery of hydrophilic proteins is an important therapeutic strategy. However, widely used methods for protein delivery suffer from low incorporation efficiency and loss of bioactivity. The versatile interfacial polyelectrolyte complexation (IPC) fibers have the capacity for precise spatiotemporal release and protection of protein, growth factor, and cell bioactivity. Yet its weak mechanical properties limit its application and translation into a viable clinical solution. To overcome this limitation, IPC fibers can be incorporated into polymeric scaffolds such as the biocompatible poly(vinyl alcohol) hydrogel (PVA). Therefore, we explored the use of a composite scaffold of PVA and IPC fibers for controlled biomolecule release. We first observed that the permeability of biomolecules through PVA films were dependent on molecular weight. Next, IPC fibers were incorporated in between layers of PVA to produce PVA–IPC composite scaffolds with different IPC fiber orientation. The composite scaffold demonstrated excellent mechanical properties and efficient biomolecule incorporation. The rate of biomolecule release from PVA–IPC composite grafts exhibited dependence on molecular weight, with lysozyme showing near-linear release for 1 month. Angiogenic factors were also incorporated into the PVA–IPC grafts, as a potential biomedical application of the composite graft. While vascular endothelial growth factor only showed a maximum cumulative release of 3%, the smaller PEGylated-QK peptide showed maximum release of 33%. Notably, the released angiogenic biomolecules induced endothelial cell activity thus indicating retention of bioactivity. We also observed lack of significant macrophage response against PVA–IPC grafts in a rabbit model. Showing permeability, mechanical strength, precise temporal growth factor release, and bioinertness, PVA–IPC fibers composite scaffolds are excellent scaffolds for controlled biomolecule delivery in soft tissue engineering.

The endothelial lining of blood vessels is severely affected in type II diabetes. Yet, there is still a paucity on the use of diabetic endothelial cells for study and assessment of implantable devices targeting vascular disease. This critically impairs our ability to determine appropriate topographical cues to be included in implantable devices that can be used to maintain or improve endothelial cell function in vivo. Here, the functional responses of healthy and diabetic human coronary arterial endothelial cells were studied and observed to differ depending on topography. Gratings (2 μm) maintained normal endothelial functions such as adhesiveness, angiogenic capacity and cell-cell junction formation, and reduced immunogenicity of healthy cells. However, a significant and consistent effect was not observed in diabetic cells. Instead, diabetic endothelial cells cultured on the perpendicularly aligned multi-scale hierarchical gratings (250 nm gratings on 2 μm gratings) drastically reduced the uptake of oxidized low-density lipoprotein, decreased immune activation, and accelerated cell migration. Concave microlens (1.8 μm diameter) topography was additionally observed to overwhelmingly deteriorate diabetic endothelial cell function. The results of this study support a new paradigm and approach in the design and testing of implantable devices and biomedical interventions for diabetic patients.

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