Abstract
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.
Highlights
Controlled delivery of hydrophilic, protein-based drugs is widely explored for treatment of various diseases
We explored the use of a composite scaffold of Interfacial polyelectrolyte complexation (IPC) fiber and poly(vinyl alcohol) hydrogel (PVA) hydrogel (PVA–IPC fiber composite) as a vehicle for the temporally controlled release of hydrophilic biomolecules
We observed that elastic moduli of PVA–IPC composite films were statistically similar regardless of IPC fiber presence or orientation (Figure 3A), yet maximum tensile strength of each PVA–IPC film was significantly higher than the plain PVA (Figure 3B)
Summary
Controlled delivery of hydrophilic, protein-based drugs is widely explored for treatment of various diseases. Interfacial polyelectrolyte complexation (IPC) fibers have the characteristics that are especially pertinent for controlled release of protein-based therapeutics such as growth factors. IPC fibers have been utilized for precise spatiotemporal delivery of various biomolecules such as small drugs (Liao et al, 2005), large protein growth factors (Cutiongco et al, 2014; Teo et al, 2014), or even cells (Yim et al, 2006). High incorporation efficiency of potentially any type of biomolecule is possible with its addition to the charged polyelectrolyte (Cutiongco et al, 2014).
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