The endothelial glycocalyx lining the inside surfaces of blood vessels has multiple features that prevent inflammation, blood clot formation, and infection. This surface represents the highest standard in blood compatibility for long-term contact with blood under physiological flow rates. Engineering materials used in blood-contacting biomedical devices, including metals and polymers, have undesirable interactions with blood that lead to failure modes associated with inflammation, blood clotting, and infection. Platelet adhesion and activation are key events governing these undesirable interactions. In this work, we propose a new surface modification to titanium with three features inspired by the endothelial glcyocalyx: First, titanium surfaces are anodized to produce titania nanotubes with high surface area. Second, the nanostructured surfaces are coated with heparin–chitosan polyelectrolyte multilayers to provide glycosaminoglycan functionalization. Third, chitosan is modified with a nitric oxide-donor chemistry to provide an important antithrombotic small-molecule signal. We show that these surfaces are nontoxic with respect to platelets and leukocytes. The combination of glycocalyx-inspired features results in a dramatic reduction of platelet and leukocyte adhesion and platelet activation.

Critical-sized long bone defects suffer from complications including impaired healing and non-union due to substandard healing and integration of devitalized bone allograft. Removal of the periosteum contributes to the limited healing of bone allografts. Restoring a periosteum on bone allografts may provide improved allograft healing and integration. This article reports a polysaccharide-based tissue engineered periosteum that delivers basic fibroblast growth factor (FGF-2), transforming growth factor-β1 (TGF-β1), and adipose-derived mesenchymal stem cells (ASCs) to a critical-sized mouse femur defect. The tissue engineered periosteum was evaluated for improving bone allograft healing and incorporation by locally delivering FGF-2, TGF-β1, and supporting ASCs transplantation. ASCs were successfully delivered and longitudinally tracked at the defect site for at least 7 days post operation with delivered FGF-2 and TGF-β1 showing a mitogenic effect on the ASCs. At 6 weeks post implantation, data showed a non-significant increase in normalized bone callus volume. However, union ratio analysis showed a significant inhibition in allograft incorporation, confirmed by histological analysis, due to loosening of the nanofiber coating from the allograft surface. Ultimately, this investigation shows our tissue engineered periosteum can deliver FGF-2, TGF-β1, and ASCs to a mouse critical-sized femur defect and further optimization may yield improved bone allograft healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 900-911, 2017.

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Polyelectrolyte multilayers (PEMs) of chitosan and heparin are useful for mimicking growth factor (GF) binding to extracellular matrix (ECM) as in vivo. Here, we developed a PEM platform for delivering bound/adsorbed GFs to monocultures of primary human hepatocytes (PHHs) and PHH/non-parenchymal cell (NPC) co-cultures, which are useful for drug development and regenerative medicine. The effects of ECM protein coating (collagen I, fibronectin, and Matrigel®) and terminal PEM layer on PHH attachment/functions were determined. Then, heparin-terminated/fibronectin-coated PEMs were used to deliver varying concentrations of an adsorbed model GF, transforming growth factor β (TGFβ), to PHH monocultures while using soluble TGFβ delivery via culture medium as the conventional control. Soluble TGFβ delivery caused a severe, monotonic, and sustained downregulation of all PHH functions measured (albumin and urea secretions, cytochrome-P450 2A6 and 3A4 enzyme activities), whereas adsorbed TGFβ delivery caused transient upregulation of 3 out of 4 functions. Finally, functionally stable co-cultures of PHHs and 3T3-J2 murine embryonic fibroblasts were created on the heparin-terminated/fibronectin-coated PEMs modified with adsorbed TGFβ to elucidate similarities and differences in functional response relative to the monocultures. In conclusion, chitosan-heparin PEMs constitute a robust platform for investigating the effects of GF delivery modes on PHH monocultures and PHH/NPC co-cultures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 971-984, 2018.