A B S T R A C TFor over ten years, metallic skeletal endoprostheses have been produced in select cases by additive manufacturing (AM) and increasing awareness is driving demand for wider access to the technology. This review brings together key stakeholder perspectives on the translation of AM research; clinical application, ongoing research in the field of powder bed fusion, and the current regulatory framework. The current clinical use of AM is assessed, both on a mass-manufactured scale and bespoke application for patient specific implants. To illuminate the benefits to clinicians, a case study on the provision of custom cranioplasty is provided based on prosthetist testimony. Current progress in research is discussed, with immediate gains to be made through increased design freedom described at both meso-and macro-scale, as well as long-term goals in alloy development including bioactive materials. In all cases, focus is given to specific clinical challenges such as stress shielding and osseointegration. Outstanding challenges in industrialisation of AM are openly raised, with possible solutions assessed. Finally, overarching context is given with a review of the regulatory framework involved in translating AM implants, with particular emphasis placed on customisation within an orthopaedic remit. A viable future for AM of metal implants is presented, and it is suggested that continuing collaboration between all stakeholders will enable acceleration of the translation process. fection or surgical complications [11][12][13].Currently, the majority of skeletal endoprostheses are produced from titanium (Ti) or cobalt chromium (CoCr) based alloys, which meet the criteria of durability, strength, corrosion resistance and a low immune response [14,15]. These characteristics however come at the cost of the high stiffness of these alloys in comparison to bone. Mismatch between the mechanical properties of bone and orthopaedic materials

Extracellular Vesicles (EVs) are considered promising nanoscale therapeutics for bone regeneration. To date, EVs are typically procured from cells on 2D tissue culture plastic, an artificial environment that limits cell growth and does not replicate in situ biochemical or biophysical conditions. This study investigated the potential of 3D printed titanium scaffolds coated with hydroxyapatite to promote the therapeutic efficacy of osteoblast-derived EVs. Ti6Al4V titanium scaffolds with different pore sizes (500 and 1000 µm) and shapes (square and triangle) were fabricated by selective laser melting. A bone-mimetic nano-needle hydroxyapatite (nnHA) coating was then applied. EVs were procured from scaffold-cultured osteoblasts over 2 weeks and vesicle concentration was determined using the CD63 ELISA. Osteogenic differentiation of human bone marrow stromal cells (hBMSCs) following treatment with primed EVs was evaluated by assessing alkaline phosphatase activity, collagen production and calcium deposition. Triangle pore scaffolds significantly increased osteoblast mineralisation (1.5-fold) when compared to square architectures (P ≤ 0.001). Interestingly, EV yield was also significantly enhanced on these higher permeability structures (P ≤ 0.001), in particular (2.2-fold) for the larger pore structures (1000 µm). Furthermore osteoblast-derived EVs isolated from triangular pore scaffolds significantly increased hBMSCs mineralisation when compared to EVs acquired from square pore scaffolds (1.7-fold) and 2D culture (2.2-fold) (P ≤ 0.001). Coating with nnHA significantly improved osteoblast mineralisation (>2.6-fold) and EV production (4.5-fold) when compared to uncoated scaffolds (P ≤ 0.001). Together, these findings demonstrate the potential of harnessing bone-mimetic culture platforms to enhance the production of pro-regenerative EVs as an acellular tool for bone repair.

The global surge of antimicrobial resistance (AMR) is a major concern for public health and proving to be a key challenge in modern disease treatment, requiring action plans at all levels.

Corneal transplantation is the current gold standard treatment to restore visual acuity to patients with severe corneal diseases and injuries. Due to severe donor tissue shortage, efforts to develop a corneal equivalent have been made but the challenge remains unmet. Another issue of concern in ocular surgery is the difficult instillation and fast drainage of antibiotic ocular eye drops as bacterial infections can jeopardize implant success by delaying or impairing tissue healing. In this study, we developed antimicrobial silk‐based hydrogels that have the potential to be photoactivated in situ, fully adapting to the corneal injury shape. Gentamicin‐loaded methacrylated‐silk (SilkMA) hydrogels were prepared within minutes using low UV intensity (3 mW/cm2). SilkMA gels provided a Young's modulus between 21 and 79 kPa together with a light transmittance spectrum and water content (83%–90%) similar to the human cornea. Polymer concentration (15%–25%) was found to offer a tool for tailoring the physical properties of the hydrogels. We confirmed that the methacrylation did not affect the material's in vitro degradation and biocompatibility by observing fibroblast adhesion and proliferation. Importantly, agar diffusion tests showed that the synthesized hydrogels were able to inhibit Staphylococcus aureus and Pseudomonas aeruginosa growth for 72 h. These characteristics along with their injectability and viscoelasticity demonstrate the potential of SilkMA hydrogels to be applied in several soft tissue engineering fields. As such, for the first time we demonstrate the potential of photocurable antimicrobial SilkMA hydrogels as a novel biomaterial to facilitate corneal regeneration.

Purpose Selective laser melting (SLM) is increasingly used to manufacture bone implants from titanium alloys with particular interest in porous lattice structures. These complex constructs have been shown to be capable of matching native bone mechanical behaviour leading to improved osseointegration while providing numerous clinical advantages, encouraging their broad use in medical devices. However, producing lattices with a strut diameter similar in scale to a typical SLM melt pool or using the same process parameters and scan strategies intended for bulk solid components may lead to geometric inaccuracies. The purpose of this study is to evaluate and optimise the single contour strategy for the production of Ti-6Al-4V lattices. Design/methodology/approach Herein, the potential of an unfilled single contour (SC) scanning strategy to improve the reproducibility of porous lattices when compared with a single contour and fill approach (SC + F) is explored. For this purpose, two parametric analysis were carried out on Ti-6Al-4V diamond unit cell lattices with different strut sizes and scan strategies. Porosity and accuracy measurements were correlated with processing parameters and printing strategy to provide the optimal processing window for lattice manufacturing. Findings SC is shown to be a viable strategy for production of Ti-6Al-4V lattices with a strut diameter below 350 µm. Parametric analysis highlights the limits of this method in producing fully dense struts with energy density presented as a useful practical tool to guide some aspects of parameter selection (design strut diameter achieved at approximately 0.1 J/mm in this study). Finally, a process map combining data from both parametric studies is provided to guide, predict and control lattice strut geometry and porosity obtained using the SC strategy. Originality/value These results explore the use of non-standard SC scanning strategy as a viable method for producing strut-based lattice structures and compare against the traditional contour and fill approach (SC + F).

Biomedical prostheses are artificial devices suitable for the replacement of missing or inefficient parts of the body, implanted to reduce the anatomical or functional deficiency, and sometimes also applied for aesthetic purposes. Despite this type of medical devices represents today a very innovative sector from the medical and engineering point of view, some issues, inherent to the interaction between human body and the external hosts must be considered. It is important that the weight and porosity of the prosthesis respect the patient’s physiological equilibrium which permit an appropriate osseointegration where needed. A typical solution is a lattice structure, which can be manufactured by Additive Manufacturing techniques which, as known, permit to build complex geometries in comparison with other processing routes. Lattice structure are typically characterized by both stiffness and strength significantly lower than the full part of the structure. Generally, for this reason, the lattices are applied to the low-stress areas, leaving a portion of solid sufficient to transmit the loads involved, or in such a way to guarantee the desired flexibility of the part-itself. During the design of lattices some limitations regarding their printability must be considered, such as the minimum printable dimension and the necessary support parts. A Design of Experiment analysis was conducted to identify the optimal parameters to manufacture a spinal cage with negligible porosity via laser powder bed fusion using Ti6Al4V alloy.