Surface Functionalization of Titanium with Carboxymethyl Chitosan and Immobilized Bone Morphogenetic Protein-2 for Enhanced Osseointegration

Abstract

Orthopedic implant failure has been attributed mainly to loosening of the implant from host bone, which may be due to poor bonding of the implant material to bone tissue, as well as to bacterial infection. One promising strategy to enhance tissue integration is to develop a selective biointeractive surface that simultaneously enhances bone cell function while decreasing bacterial adhesion. In this in vitro study, the surfaces of titanium alloy substrates were functionalized by first covalently grafting carboxymethyl chitosan (CMCS), followed by the conjugation of bone morphogenetic protein-2 (BMP-2) to the CMCS-grafted surface. Bacterial adhesion on the substrates was assayed with Staphylococcus aureus and Staphylococcus epidermidis . Cell functions were investigated using osteoblasts and human bone marrow-derived mesenchymal stem cells. The results showed that bacterial adhesion on both the CMCS and CMCS-BMP-2 functionalized surfaces was significantly reduced compared to that on the pristine substrates. In addition, the CMCS-BMP-2 modified substrates significantly promoted attachment, alkaline phosphatase activity, and calcium mineral deposition of both osteoblast and human bone marrow-derived mesenchymal stem cells. The achievement of the dual functions of bacterial adhesion reduction and cell function promotion by the CMCS-BMP-2 modified titanium substrates illustrates the good potential of such surfaces for enhancement of tissue integration and implant longevity.

Effects of Immobilizations of rhBMP-2 and/or rhPDGF-BB on Titanium Implant Surfaces on Osseointegration and Bone Regeneration

“…XPS showed heparin was successfully grafted on anodized Ti surfaces, as indicated by higher C and N peaks. In a previous study, successful immobilization of rhBMP-2 on surface of carboxymethyl chitosan (CMCS)-grafted Ti was attributed to the covalent bonds formation between the carboxyl groups of CMCS and the amine groups of rhBMP-2 [53]. In the present study, successful anchoring of rhBMP-2 and rhPDGF-BB to Hepa/Ti surfaces was demonstrated by further increases in N content.…”

Antimicrobial dental implant functionalization strategies —A systematic review

“…Some polymeric surfaces consist of hydrophilic, highly hydrated, non-charged surfaces to reduce any surface interactions. Dextran and polyethylene glycol (PEG) surfaces have been shown to be effective in suppressing protein adhesion, platelet adhesion, bacterial adhesion and biofilm formation of oral relevant pathogens, such as S. aureus, S. sanguinis, L. salivarius S. mutans and S.gordonii 29,96,[101][102][103]107) . Lignin, a complex, amorphous organic polymer found in plant tissues, exhibits antibacterial activity against S. aureus, P. aeruginosa and C. famata 51) .…”

“…For instance, PEG surfaces hinder not only non-specific protein adsorption and bacterial attachment but, to the same degree, the adhesion of mammalian cells. Recent studies have attempted to promote specific binding interactions between host tissues and implant materials by immobilizing bioactive proteins, such as cell adhesive proteins containing arginine-glycine-aspartic acid (RGD) sequences or bone morphogenetic proteins 28,29,98,99,112,163) . Peptide-functionalized polymers exhibit a selective biointeraction pattern that may be useful in dental implantology, as they can enhance attachment of fibroblasts and osteoblasts while reducing non-specific protein adsorption, thus resulting in reduced bacterial adherence.…”

Bifunctional Eu3+‐doped Gd2O3 nanoparticles as a luminescent and T1 contrast agent for stem cell labeling

“…The medium was changed twice per week. Alkaline phosphatase activity (ALP) was determined after 1 and 2 weeks as previously described (31). Briefly, the cell layers were first washed with PBS.…”