RESUMO
There is a substantial global market for orthopedic implants, but these implants still face the problem of a high failure rate in the short and long term after implantation due to the complex physiological conditions in the body. The use of multifunctional coatings on orthopedic implants has been proposed as an effective way to overcome a range of difficulties. Here, a multifunctional (TA@HA/Lys)n coating composed of tannic acid (TA), hydroxyapatite (HA), and lysozyme (Lys) was fabricated in a layer-by-layer (LBL) manner, where TA deposited onto HA firmly stuck Lys and HA together. The deposition of TA onto HA, the growth of (TA@HA/Lys)n, and multiple related biofunctionalities were thoroughly investigated. Our data demonstrated that such a hybrid coating displayed antibacterial and antioxidant effects, and also facilitated the rapid attachment of cells [both mouse embryo osteoblast precursor cells (MC3T3-E1) and dental pulp stem cells (DPSCs)] in the early stage and their proliferation over a long period. This accelerated osteogenesis in vitro and promoted bone formation in vivo. We believe that our findings and the developed strategy here could pave the way for multifunctional coatings not only on orthopedic implants, but also for additional applications in catalysts, sensors, tissue engineering, etc.
RESUMO
We describe a pH-indicating material that can be directly implanted or coated on orthopedic implant surfaces to provide high-spatial-resolution pH mapping through tissue by X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting local pH changes during treatment of implant-associated infections. The material has two layers: an X-ray scintillator layer with Gd2O2S:Eu in epoxy, which emits 620 and 700 nm light when irradiated with X-rays, and a pH indicator dye layer, which absorbs some of the 620 nm light in a pH-dependent fashion. To acquire each pixel in the image, a focused X-ray beam irradiates a small region of scintillators and the ratio of 620 to 700 nm light is acquired through the tissue. Scanning the X-ray beam across the implant surface generates high-spatial-resolution chemical measurements. Two associated challenges are (1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations specifically for metal orthopedic implants and (2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor onto the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein, we describe a chemically sensitive and biocompatible XELCI sensor material that can conformally coat the implant surface. A two-part commercial-grade epoxy resin was mixed with Gd2O2S:Eu and adhered to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase the surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This combination of epoxy-PEG layers was found to adhere well to the metal implant unlike other previously tested polymer surfaces, which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm-thick tissue. The pH sensor-coated orthopedic plate was imaged with XELCI, through tissue, with different pH levels to acquire a calibration curve. The plates were also imaged through tissue, with a low pH region on one section due to growth of a Staphylococcus aureus biofilm. A pH sensor-coated stainless-steel rod with two distinct pH regions was inserted in a rabbit tibia specimen, and the pH was imaged through both bone and soft tissue. These studies demonstrate the use of pH sensor-coated orthopedic plates and rods for mapping the local pH through tissue during biofilm formation by XELCI.