Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed.

The potential to bioprint and study 3D bacterial biofilm constructs could have great clinical significance at a time when antimicrobial resistance is rising to dangerously high levels worldwide. In this study, clinically relevant bacterial species including Escherichia coli, Staphylococcus aureus (MSSA), Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were 3D bioprinted using a double-crosslinked alginate bioink to form mature bacteria biofilms, characterized by confocal laser scanning microscopy (CLSM) and fluorescent staining. Solid and porous bacteria-laden constructs were reproducibly bioprinted with thicknesses ranging from 0.25 to 4 mm. We demonstrated 3D bioprinting of thicker biofilms (>4 mm) than found in currently available in vitro models. Bacterial viability was excellent in the bioprinted constructs, with CLSM observation of bacterial biofilm production and maturation possible for at least 28 d in culture. Importantly, we observed the complete five-step biofilm life cycle in vitro following 3D bioprinting for the first time, suggesting the formation of mature 3D bioprinted biofilms. Bacterial growth was faster in thinner, more porous constructs whilst constructs crosslinked with BaCl2 concentrations of above 10 mM had denser biofilm formation. 3D MRSA and MSSA biofilm constructs were found to show greater resistance to antimicrobials than corresponding two-dimensional (2D) cultures. Thicker 3D E. coli biofilms had greater resistance to tetracycline than thinner constructs over 7 d of treatment. Our methodology allowed for the precise 3D bioprinting of self-supporting 3D bacterial biofilm structures that developed biofilms during extended culture. 3D biofilm constructs containing bacterial biofilms produce a model with much greater clinical relevance compared to 2D culture models and we have demonstrated their use in antimicrobial testing.

Soft tissue injuries (STIs) affect patients of all age groups and represent a common worldwide clinical problem, resulting from conditions including trauma, infection, cancer and burns. Within the spectrum of STIs a mixture of tissues can be injured, ranging from skin to underlying nerves, blood vessels, tendons and cartilaginous tissues. However, significant limitations affect current treatment options and clinical demand for soft tissue and cartilage regenerative therapies continues to rise.Improving the regeneration of soft tissues has therefore become a key area of focus within tissue engineering. As an emerging technology, 3D bioprinting can be used to build complex soft tissue constructs "from the bottom up," by depositing cells, growth factors, extracellular matrices and other biomaterials in a layer-by-layer fashion. In this way, regeneration of cartilage, skin, vasculature, nerves, tendons and other bodily tissues can be performed in a patient specific manner. This review will focus on recent use of 3D bioprinting and other biofabrication strategies in soft tissue repair and regeneration. Biofabrication of a variety of soft tissue types will be reviewed following an overview of available cell sources, bioinks and bioprinting techniques.

We compared lower limb coronal alignment measurements obtained pre- and post-operatively with long-leg radiographs and computer navigation in patients undergoing primary total knee replacement (TKR). A series of 185 patients had their pre- and post-implant radiological and computer-navigation system measurements of coronal alignment compared using the Bland-Altman method. The study included 81 men and 104 women with a mean age of 68.5 years (32 to 87) and a mean body mass index of 31.7 kg/m(2) (19 to 49). Pre-implant Bland-Altman limits of agreement were -9.4° to 8.6° with a repeatability coefficient of 9.0°. The Bland-Altman plot showed a tendency for the radiological measurement to indicate a higher level of pre-operative deformity than the corresponding navigation measurement. Post-implant limits of agreement were -5.0° to 5.4° with a repeatability coefficient of 5.2°. The tendency for valgus knees to have greater deformity on the radiograph was still seen, but was weaker for varus knees. The alignment seen or measured intra-operatively during TKR is not necessarily the same as the deformity seen on a standing long-leg radiograph either pre- or post-operatively. Further investigation into the effect of weight-bearing and surgical exposure of the joint on the mechanical femorotibial angle is required to enable the most appropriate intra-operative alignment to be selected.

The quantification of knee alignment is a routine part of orthopaedic practice and is important for monitoring disease progression, planning interventional strategies, and follow-up of patients. Currently available technologies such as radiographic measurements have a number of drawbacks. The aim of this study was to validate a potentially improved technique for measuring knee alignment under different conditions. An image-free navigation system was adapted for non-invasive use through the development of external infrared tracker mountings. Stability was assessed by comparing the variance (F-test) of repeated mechanical femoro-tibial (MFT) angle measurements for a volunteer and a leg model. MFT angles were then measured supine, standing and with varus-valgus stress in asymptomatic volunteers who each underwent two separate registrations and repeated measurements for each condition. The mean difference and 95% limits of agreement were used to assess intra-registration and inter-registration repeatability. For multiple registrations the range of measurements for the external mountings was 1 larger than for the rigid model with statistically similar variance ( p ¼ 0.34). Thirty volunteers were assessed (19 males, 11 females) with a mean age of 41 years (range: 20-65) and a mean BMI of 26 (range: 19-34). For intra-registration repeatability, consecutive coronal alignment readings agreed to almost AE1, with up to AE0.5 loss of repeatability for coronal alignment measured before and after stress maneuvers, and a AE0.2 loss following stance trials. Sagittal alignment measurements were less repeatable overall by an approximate factor of two. Inter-registration agreement limits for coronal and sagittal supine MFT angles were AE1.6 and AE2.3 , respectively. Varus and valgus stress measurements agreed to within AE1.3 and AE1.1 , respectively. Agreement limits for standing MFT angles were AE2.9(coronal) and AE5.0 (sagittal), which may have reflected a variation in stance between measurements. The system provided repeatable, real-time measurements of coronal and sagittal knee alignment under a number of dynamic, real-time conditions, offering a potential alternative to radiographs.