Advancing of 3D-Printed Titanium Implants with Combined Antibacterial Protection Using Ultrasharp Nanostructured Surface and Gallium-Releasing Agents.

This paper presents the development of advanced Ti implants with enhanced antibacterial activity. The implants were engineered using additive manufacturing three-dimensional (3D) printing technology followed by surface modification with electrochemical anodization and hydrothermal etching, to create unique hierarchical micro/nanosurface topographies of microspheres covered with sharp nanopillars that can mechanically kill bacteria in contact with the surface. To achieve enhanced antibacterial performance, fabricated Ti implant models were loaded with gallium nitrate as an antibacterial agent. The antibacterial efficacy of the fabricated substrates with the combined action of sharp nanopillars and locally releasing gallium ions (Ga3+) was evaluated toward Staphylococcus aureus and Pseudomonas aeruginosa. Results confirm the significant antibacterial performance of Ga3+-loaded substrates with a 100% eradication of bacteria. The nanopillars significantly reduced bacterial attachment and prevented biofilm formation while also killing any bacteria remaining on the surface. Furthermore, 3D-printed surfaces with microspheres of diameter 5-30 µm and interspaces of 12-35 µm favored the attachment of osteoblast-like MG-63 cells, as confirmed via the assessment of their attachment, proliferation, and viability. This study provides important progress toward engineering of next-generation 3D-printed implants, that combine surface chemistry and structure to achieve a highly efficacious antibacterial surface with dual cytocompatibility to overcome the limitations of conventional Ti implants.

Advancing of Additive-Manufactured Titanium Implants with Bioinspired Micro- to Nanotopographies.

There is an increasing demand for low-cost and more efficient titanium (Ti) medical implants that will provide improved osseointegration and at the same time reduce the likelihood of infection. In the past decade, additive manufacturing (AM) using metal selective laser melting (SLM) or three-dimensional (3D) printing techniques has emerged to enable novel implant geometries or properties to overcome such potential challenges. This study presents a new surface engineering approach to create bioinspired multistructured surfaces on SLM-printed Ti alloy (Ti6Al4V) implants by combining SLM technology, electrochemical anodization, and hydrothermal (HT) processes. The resulting implants display unique surfaces with a distinctive dual micro- to nano-topography composed of micron-sized spherical features, fabricated by SLM and vertically aligned nanoscale pillar structures as a result of combining anodization and HT treatment. The fabricated implants enhanced hydroxyapatite-like mineral deposition from simulated body fluid (SBF) compared to control. In addition, normal human osteoblast-like cells (NHBCs) showed strong adhesion to the nano-/microstructures and displayed greater propensity to mineralize compared to control surfaces. This engineering approach and the resulting nature-inspired multiscale-structured surface offers desired features for improving osseointegration and antibacterial performance toward the development of next-generation orthopedic and dental implants.

Micro- and nano-structured 3D printed titanium implants with a hydroxyapatite coating for improved osseointegration.

With the increasing demand for low-cost and more efficient dental implants, there is an urgent need to develop new manufacturing approaches and implants with better osseointegration performance. 3D printing technology provides enormous opportunities for the rapid fabrication of a new generation of patient-tailored dental implants with significantly reduced costs. This study presents the demonstration of a unique model of titanium implants based on 3D printing technology with improved osseointegration properties. Titanium alloy (Ti6Al4V) implants with a micro-structured surface are fabricated using a selective laser-melting process followed by further nano-structuring with electrochemical anodization to form titania nanotubes (TNT) and subsequent bioactivation by a hydroxyapatite (HA) coating. The osseointegration properties of the fabricated implants were examined using human primary osteoblasts and cell line models. The results showed significantly increased protein adsorption, cell adhesion and cell spreading. The expression of the late osteoblast/osteocyte genes GJA1 and PHEX was also enhanced, indicating a cell maturation effect and the promotion of mineralization on the surface. These results suggest that 3D printing technology combined with electrochemical nano-structuring and HA modification is a promising approach for the fabrication of Ti implants with improved osseointegration and provides potential alternatives to conventional dental implants.

Engineering of Micro- to Nanostructured 3D-Printed Drug-Releasing Titanium Implants for Enhanced Osseointegration and Localized Delivery of Anticancer Drugs.

Primary and secondary bone cancers are major causes of pathological bone fractures which are usually treated through implant fixation and chemotherapy. However, both approaches face many limitations. On one hand, implants may suffer from poor osseointegration, and their rejection results in repeated surgery, patient's suffering, and extensive expenses. On the other hand, there are severe systemic adverse effects of toxic chemotherapeutics which are administrated systemically. In this paper, in order to address these two problems, we present a new type of localized drug-releasing titanium implants with enhanced implants' biointegration and drug release capabilities that could provide a high concentration of anticancer drugs locally to treat bone cancers. The implants are fabricated by 3D printing of Ti alloy followed by an anodization process featuring unique micro- (particles) and nanosurface (tubular arrays) topography. We successfully demonstrate their enhanced bone osseointegration and drug loading capabilities using two types of anticancer drugs, doxorubicin (DOX) and apoptosis-inducing ligand (Apo2L/TRAIL). In vitro study showed strong anticancer efficacy against cancer cells (MDA-MB-231-TXSA), confirming that these drug-releasing implants can be used for localized chemotherapy for treatment of primary and secondary bone cancers together with fracture support.

Anodized 3D-printed titanium implants with dual micro- and nano-scale topography promote interaction with human osteoblasts and osteocyte-like cells.

The success of implantation of materials into bone is governed by effective osseointegration, requiring biocompatibility of the material and the attachment and differentiation of osteoblastic cells. To enhance cellular function in response to the implant surface, micro- and nano-scale topography have been suggested as essential. In this study, we present bone implants based on 3D-printed titanium alloy (Ti6Al4V), with a unique dual topography composed of micron-sized spherical particles and vertically aligned titania nanotubes. The implants were prepared by combination of 3D-printing and anodization processes, which are scalable, simple and cost-effective. The osseointegration properties of fabricated implants, examined using human osteoblasts, showed enhanced adhesion of osteoblasts compared with titanium materials commonly used as orthopaedic implants. Gene expression studies at early (day 7) and late (day 21) stages of culture were consistent with the Ti substrates inducing an osteoblast phenotype conducive to effective osseointegration. These implants with the unique combination of micro- and nano-scale topography are proposed as the new generation of multi-functional bone implants, suitable for addressing many orthopaedic challenges, including implant rejection, poor osseointegration, inflammation, drug delivery and bone healing. Copyright © 2016 John Wiley & Sons, Ltd.