Bone morphogenetic protein‐2 delivery from polyelectrolyte multilayers enhances osteogenic activity on nanostructured titania

Abstract

Incomplete osseointegration is primary cause of failure for orthopedic implants. New biomaterials that present stable signals promoting osteogenesis could reduce failure rates of orthopedic implants. In this study bone morphogenetic protein‐2 (BMP‐2) was delivered from titania nanotubes (Nt) modified with chitosan/heparin polyelectrolyte multilayers (PEMs). The surfaces were characterized by scanning electron microscopy and X‐ray photoelectron spectroscopy. BMP‐2 release from the surfaces was measured in vitro for up to 28 days. After an initial burst release of BMP‐2 during the first 2 days, most of the BMP‐2 remained on the surface. To determine the osteogenic properties of these surfaces, they were seeded with rat bone marrow cells; alkaline phosphatase (ALP) activity, total protein, calcium deposition, and osteocalcin were measured up to 4 weeks in vitro. When compared to Nt surfaces, the surfaces with BMP‐2 induce greater osteocalcin and calcium deposition. PEMs provide sustained presentation of BMP‐2, from a biomimetic surface. This enhances the osteogenic properties of the surface without requiring supraphysiologic growth factor dose. This growth factor delivery strategy could be used to improve bone healing outcomes and reduce complications for recipients of orthopedic implants.

Gentamicin-Releasing Titania Nanotube Surfaces Inhibit Bacteria and Support Adipose-Derived Stem Cell Growth in Cocultures

“…Nt surfaces were prepared on flat titanium foils (8 mm diameter) using a previously reported anodization process carried out at 55 V for 22 h at room temperature, followed by annealing for 3 h at 530 °C. , Nt surfaces were subsequently modified by 18-layer chitosan-heparin PEMs as previously reported by our group to obtain Nt + PEM surfaces. , Additional details of the anodization process and PEM deposition procedure are provided in the Supporting Information. The topography and chemistry of these surfaces have been extensively characterized previously using electron microscopy and X-ray spectroscopy .…”

“…Compared to those that have only a primary surgery, patients who have undergone a revision surgery experience a significant decrease in physical functioning . Antimicrobial surfaces that do not inhibit bone cell growth could prevent implant failure due to infection and avoid the increase in cost and decrease in health associated with implant failure …”

“…These characteristics make ADSCs an ideal cell source for bone tissue engineering . Nanotopographical structures can increase cellular attachment and enhance in vitro and in vivo bone formation. − We have used anodization to prepare titania nanotubes (Nts) to introduce nanoscale surface features to titanium. , The Nt modification improves cell adhesion, viability, and proliferation relative to unmodified titanium . Human ADSCs (hADSCs) cultured on Nt surfaces had improved osteogenic markers compared to hADSCs cultured on titanium, suggesting that the nanotopography accelerates hADSC differentiation into an osteogenic phenotype .…”

“…Nanotubes loaded with gentamicin may inhibit bacterial adhesion without causing cytoxicity . Tunable amounts of gentamicin can be delivered using polyelectrolyte multilayers (PEMs). ,,, Our group has also modified Nt surfaces with polysaccharide-containing PEMs, with thicknesses ranging from 10 to 20 nm. ,, …”

“…aureus bacteria. Chitosan/heparin PEMs were adsorbed onto nanotubes because heparin and chitosan have antimicrobial properties and heparin has been used to bind gentamicin to surfaces. ,− ,,,, Chitosan/heparin PEMs can present bone morphogenetic protein 2 (BMP-2) on nanotubes and increase the osteogenic responses of bone marrow cells for up to 4 weeks in vitro . While previous studies have tested the antimicrobial properties of surfaces and cellular attachment, very few have cocultured mammalian cells with bacteria to determine whether surfaces can simultaneously inhibit bacteria and promote mammalian cell attachment. ,− ,,,,− Infection of a prosthetic implant is described as a “race to the surface,” in which the chance of infection is determined by which colonizes the surfaces first, bacteria or osteogenic cells.…”