Biocompatibility of Common Implantable Sensor Materials in a Tumor Xenograft Model

Real-time monitoring of tumor microenvironment parameters using an implanted biosensor could provide valuable information on the dynamic nature of a tumor's biology and its response to treatment. However, following implantation biosensors may lose functionality due to biofouling caused by the foreign body response (FBR). This study developed a novel tumor xenograft model to evaluate the potential of six biomaterials (silicon dioxide, silicon nitride, Parylene-C, Nafion, biocompatible EPOTEK epoxy resin, and platinum) to trigger a FBR when implanted into a solid tumor. Biomaterials were chosen based on their use in the construction of a novel biosensor, designed to measure spatial and temporal changes in intra-tumoral O2 , and pH. None of the biomaterials had any detrimental effect on tumor growth or body weight of the murine host. Immunohistochemistry showed no significant changes in tumor necrosis, hypoxic cell number, proliferation, apoptosis, immune cell infiltration, or collagen deposition. The absence of biofouling supports the use of these materials in biosensors; future investigations in preclinical cancer models are required, with a view to eventual applications in humans. To our knowledge this is the first documented investigation of the effects of modern biomaterials, used in the production of implantable sensors, on tumor tissue after implantation. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B, 2018

Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium

Deborah Gorth,1 Sabrina Puckett,1 Batur Ercan,1 Thomas J Webster,1 Mohamed Rahaman,2 B Sonny Bal31School of Engineering and Department of Orthopaedics, Brown University, Providence, RI, 2Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO, 3Department of Orthopaedic Surgery, School of Medicine, University of Missouri, Columbia, MO, USAAbstract: A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants – titanium (Ti), poly-ether-ether-ketone (PEEK), and silicon nitride (Si3N4) – were tested to understand their respective susceptibility to bacterial infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface chemistry, wettability, and nanostructured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization, and growth were investigated. Ti and PEEK were received with as-machined surfaces; both materials are hydrophobic, with net negative surface charges. Two surface finishes of Si3N4 were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of Si3N4 is hydrophilic, with a net positive charge. A decreased biofilm formation was found, as well as fewer live bacteria on both the as-fired and polished Si3N4. These differences may reflect differential surface chemistry and surface nanostructure properties between the biomaterials tested. Because protein adsorption on material surfaces affects bacterial adhesion, the adsorption of fibronectin, vitronectin, and laminin on Ti, PEEK, and Si3N4 were also examined. Significantly greater amounts of these proteins adhered to Si3N4 than to Ti or PEEK. The findings of this study suggest that surface properties of biomaterials lead to differential adsorption of physiologic proteins, and that this phenomenon could explain the observed in-vitro differences in bacterial affinity for the respective biomaterials. Intrinsic biomaterial properties as they relate to resistance to bacterial colonization may reflect a novel strategy toward designing future orthopedic implants.Keywords: silicon nitride, nanostructure, anti-infective, biofilm, protein adsorptio

Development of a SiYAlON glaze for improved osteoconductivity of implantable medical devices

The application of bioactive coatings onto orthopaedic appliances is commonly performed to compensate for the otherwise bioinert nature of medical devices and to improve their osseointegration. Calcium phosphates, hydroxyapatite (HAp), and bioglasses are commercially available for this purpose. Until recently, few other inorganic compounds have been identified with similar biofunctionality. However, silicon nitride (Si3N4) has emerged as a new orthopaedic material whose unique surface chemistry also enhances osteoconductivity. Recent research has confirmed that its minority intergranular phase, consisting of silicon yttrium aluminum oxynitride (SiYAlON), is principally responsible for this improvement. As a result, it was hypothesized that SiYAlON itself might serve as an effective osteoconductive coating or glaze for medical devices. To test this hypothesis, a process inspired by traditional ceramic whiteware glazing was developed. A slurry containing ingredients similar to the intergranular SiYAlON composition was applied to a Si3N4 surface, which was then subjected to a heat treatment to form a glaze. Various analytical tools were employed to assess its chemistry and morphology. It was found that the glaze was comprised predominately of Y5Si3O12N, a compound commonly referred to as N-apatite, which is isostructural to native HAp. Subsequent exposure of the glazed surface to acellular simulated body fluid led to increased deposition of biomimetic HAp-like crystals, while exposure to Saos-2 osteosarcoma cells in vitro resulted in greater HAp deposition relative to control samples. The observation that SiYAlON exhibits enhanced osteoconductivity portends its potential as a therapeutic aid in bone and tissue repair. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1084-1096, 2018

Silicon Nitride: A Synthetic Mineral for Vertebrate Biology

The remarkable stoichiometric flexibility of hydroxyapatite (HAp) enables the formation of a variety of charged structural sites at the material’s surface which facilitates bone remodeling due to binding of biomolecule moieties in zwitterionic fashion. In this paper, we report for the first time that an optimized biomedical grade silicon nitride (Si(3)N(4)) demonstrated cell adhesion and improved osteoconductivity comparable to highly defective, non-stoichiometric natural hydroxyapatite. Si(3)N(4)’s zwitterionic-like behavior is a function of the dualism between positive and negative charged off-stoichiometric sites (i.e., N-vacancies versus silanols groups, respectively). Lattice defects at the biomaterial’s surface greatly promote interaction with positively- and negatively-charged functional groups in biomolecules, and result in the biologically effective characteristics of silicon nitride. These findings are anticipated to be a starting point for further discoveries of therapeutic bone-graft substitute materials