Quaternized Chitosan/Heparin Polyelectrolyte Multilayer Films for Protein Delivery.
Tomasz UrbaniakGabriela S García-BrionesAlexander ZhigunovSviatoslav HladyshEdyta AdrianVolodymyr LobazTereza KrunclováOlga JanouškováOgnen Pop-GeorgievskiDana KubiesPublished in: Biomacromolecules (2022)
Layer-by-layer (LbL) polyelectrolyte coatings are intensively studied as reservoirs of bioactive proteins for modulating interactions between biomaterial surfaces and cells. Mild conditions for the incorporation of growth factors into delivery systems are required to maintain protein bioactivity. Here, we present LbL films composed of water-soluble N -[(2-hydroxy-3-trimethylammonium)propyl] chitosan chloride (HTCC), heparin (Hep), and tannic acid (TA) fabricated under physiological conditions with the ability to release heparin-binding proteins. Surface plasmon resonance analysis showed that the films formed on an anchoring HTCC/TA bilayer, with TA serving as a physical crosslinker, were more stable during their assembly, leading to increased film thickness and increased protein release. X-ray reflectivity measurements confirmed intermixing of the deposited layers. Protein release also increased when the proteins were present as an integral part of the Hep layers rather than as individual protein layers. The 4-week release pattern depended on the protein type; VEGF, CXCL12, and TGF-β1 exhibited a typical high initial release, whereas FGF-2 was sustainably released over 4 weeks. Notably, the films were nontoxic, and the released proteins retained their bioactivity, as demonstrated by the intensive chemotaxis of T-lymphocytes in response to the released CXCL12. Therefore, the proposed LbL films are promising biomaterial coating candidates for stimulating cellular responses.
Keyphrases
- room temperature
- protein protein
- venous thromboembolism
- binding protein
- amino acid
- high resolution
- clinical trial
- magnetic resonance imaging
- computed tomography
- physical activity
- randomized controlled trial
- signaling pathway
- escherichia coli
- hyaluronic acid
- mass spectrometry
- optical coherence tomography
- oxidative stress
- reduced graphene oxide
- carbon nanotubes
- double blind
- biofilm formation
- placebo controlled
- electron microscopy
- dual energy