Tailoring selective laser melting process for titanium drug-delivering implants with releasing micro-channels

Abstract

The use of drug-delivering implants can minimise implant failure due to infection through a controlled medication release into the surrounding tissues. In this study, selective laser melting (SLM) was employed to manufacture Ti-6Al-4 V samples, with internal reservoirs and releasing Micro-channels (MCs) to simulate what could be a drug-delivering orthopaedic or dental implant. Investigations were performed to optimise the design and SLM process parameters required to create the releasing MCs with minimum dimensional deviation to allow a controlled dosing of the drugs, while considering the process impact on the surface roughness and porosity of the builds. The build orientation, internal contour spacing, and laser process parameters were varied to assess their effect on the resolution of the MCs with diameters of ∼200–500 μm. It was found that, vertically oriented channels were found to have the least dimensional deviation from the target dimensions compared with horizontally-oriented or inclined channels. The dimensional deviation of the MCs was found in range of 220–427 μm, while the horizontal surface roughness (R_a) was in range of 1.46–11.46 μm and the vertical surface roughness (R_a) was in range of 8.5–13.23 μm when applying energy density varying from of 27–200 J/mm³. It was found that, there was a clear correlation between the energy density with both dimensional deviation and horizontal surface roughness, while no correlation was found for the vertical’ surface roughness. The study identified the optimum conditions to manufacture drug-delivering metallic implants, creating hollow samples with releasing MCs equivalent diameter of ∼271 μm, horizontal surface roughness (R_a) of 4.4 μm, vertical surface roughness of (R_a) 9.2 μm, and build porosity of 1.4% using an internal contour of 150 μm and energy density of 35.7 J/mm³.

Introduction

The demand for implantable medical devices is being driven by population growth to over 7 billions, the ageing population in the developed countries, and improvement in the healthcare in developing countries [1]. Medical technologies that improve healthcare have become abundant, especially for traumatic injury patients or those suffering from chronic illnesses. The global sales of biomedical implants are estimated to reach $116 billion by 2022, with an annual growth rate of 7.1% from 2016 to 2022. The highest revenue-generating market in this sector is orthopaedic implants [2]. Surgeries of this type of implants have been well-established for decades, and have improved the medical conditions of patients who suffer from bone and joint problems. However, 10% of these surgeries fail [3], mainly as a result of implant failure due to infection, fibrous encapsulation, and stress shielding. Among the aforementioned reasons, implant infections account for more than 20% of orthopaedics implant failures. Although surgery rooms, equipment, and implants are sterilised, infections still do happen. If a serious infection develops, revision surgery will be needed to remove the infected implant and implant a new one [[4], [5]].

Infections in implants can be prevented through local delivery of drugs embedded within an implant (e.g. antibiotics, anti-inflammatory, pain relief, or wound-healing agents). Recently, antibiotics have been embedded in bone cement [[6], [7]]. Nonetheless, using this approach, there is no control over the drug release rates, which can either result in overdosing (i.e. toxic), or under dosing (i.e. ineffective). Furthermore, prolonged administration of an antibiotic may develop antibiotic resistance. An alternative approach to reduce or control implants-associated infections is to embed the drug within a reservoir inside the implant itself [[7], [8]]. Although, drug-eluting or drug-loaded orthopaedic implants show promising results, to date, there is no well-established manufacturing process nor clinical practice has been made for this approach, hence, further research is needed [[9], [10], [11], [12]]. Furthermore, the use of customised orthopaedic implants tailored to patients’ medical condition, bot mechanically and therapeutically, is an attractive approach to achieve better patient outcomes.

Additive Manufacturing (AM) is a game changer for several applications especially in the medical sector. Compared to other manufacturing processes, AM offers lower production costs for customised low-batch components, with reduced material waste and shorter lead-times when compared to conventional machining [[13], [14], [15]]. However, perhaps the greatest advantage, is that AM enables significant design freedom, allowing the manufacture of complex-shaped parts with that would be impossible to manufacture by conventional means [[16], [17], [18]]. Selective laser melting (SLM) is an AM process that involves the use of a laser beam to selectively melt powder layers based on a designed CAD model, resulting in fusing a series of powder layers on top of each other under an inert atmosphere to create a 3D component [19].

Titanium and its alloys have been widely used in orthopaedics and dental applications over the past few decades due to their excellent biocompatibility, superior mechanical and fatigue strength [20]. One particular alloy, Ti-6Al–4 V, has been used for orthopaedic implants for several decades. The uniqueness of this alloy is good corrosion resistance, an ability to integrate with native tissues and a Young's modulus closer to bone than stainless steels or CoCr alloys [[21], [22]]. AM of Ti-6Al-4 V orthopaedic implants has been studied by several research groups [[23], [24]]. Bracke et al. [25] studied the use of electron beam melting (EBM) as an enabling technology to produce complex and functional Ti-6Al-4 V cellular implants for the orthopaedic, dental, and maxillofacial remits, using the flexibility offered by AM to customise the implants according to patient’s geometries using Computed Tomography (CT) data. They were able to control the stiffness of the implant by manipulating the density of the cellular structures. Others such as, Wicker et al. have focused on the mechanical properties of Ti-6Al-4 V cellular knee implants manufactured by EBM [26], whereas Sun et al. used SLM to create porous medical implant scaffolds using CT data, optimising the density of the cellular structure to control bone-implant interface instability and bone resorption [27]. Okabe et al. studied the fatigue life of Ti-6Al-4 V alloy fabricated by direct-energy EBM, Direct Laser Deposition (DED), and conventional manufacturing techniques for dental implants. They found that the DED Ti-6Al-4 V parts show better fatigue life than the EBM, but a shorter fatigue life than the rolled Ti-6Al-4 V samples [28]. Despite the wealth of work on AM of medical implants, no work is available on exploiting the design freedom of AM to manufacture drug-delivering metallic implants, which is the subject of the present investigation.

In order to utilise SLM to produce a drug-delivering implant, it is essential that drug release kinetics may be controlled. Assuming that the drug is going to be contained within an internal cavity (reservoir), the delivering channels may be manipulated to enable the prediction of the release rates, while being dense and biocompatible in order to integrate with the body tissues [29]. For instance, residual porosity even with small amount can degrade the mechanical properties of the components, especially the fatigue. Therefore, the majority of recent AM research has been focused on the optimisation of the process parameters towards achieving near full density [[30], [31], [32], [33], [34]]. On the other hand, the surface topology of an implant has an important effect on the healing and integration with surrounding native tissues. Therefore, efforts have been made to control surface roughness of AM-fabricated implants in order to improve integration, particularly at the interface. In particular, surface topology plays a very important role in cell differentiation and attachment [[35], [36]]. To elicit a favourable biological response it has been recommended that the optimum surface roughness for orthopaedic implants should to be in the range R_a = 1–2 μm [37].

This work focuses on using SLM to develop drug-delivering Ti-6Al-4 V implants, with MCs that may be manipulated to control therapeutic release kinetics. The design concept of the implant is presented as a simplified cylindrical implant with a central reservoir and surface connected MCs to elute the drug within the surrounding 3D environment. The releasing MC have been designed with different sizes and orientations with respect to the SLM build direction; vertical, inclined and horizontal channels. A design of Experiment (DoE) approach was employed to study the influence of the SLM process parameters on the resolution of the MC, as well as the surface roughness and the density of the implants, which in turn are critical to implant performance.