Device associated infection (DAI) is recognized as a worldwide health challenge in total joint replacement (TJR). Bacteria exhibit very strong antibiotic tolerance when they attach to a device and form a biofilm and thus DAI is difficult to treat. In this study, a one-step, clean (no chemicals or additional materials involved) and effective surface engineering approach via laser surface treatment (LST) to tackle the DAI challenge is reported. Commercially pure (CP) Ti were laser-treated in open air using continuous wave (CW) fibre laser. The laser-treated CP Ti was tested against five bacterial species including Gram positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram negative (Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis). Live/Dead staining and image analysis results indicated that LST can significantly reduce biofilm coverage of the five tested bacterial species on the CP Ti surfaces. Overall biofilm coverage as a percentage of the surface reduced after laser treatment averaging from 4.24 % to 17.4 %. This meant that relative to the untreated surface, biofilm coverage was reduced after laser treatment, ranging from 84.9 % to 95.6 % across the five species. Furthermore, cytotoxicity results (using MTT assay) showed that the laser-treated CP Ti is non-toxic across both L929 fibroblast and RAW macrophage cell lines. Surface properties after LST were investigated using WLI and AFM (measuring micro-/nano-surface roughness and topography) as well as ToF-SIMS (measuring surface chemistry and oxide thickness), respectively. The cross-sectional microstructure at the surface was imaged using SEM and analysed by XRD, whilst the surface wettability was measured using sessile drop method. To summarise, the reduction of biofilm coverage can be attributed to the favourable changes in surface roughness and topography together with the increased concentration of oxides at the topmost surface after LST.

This chapter will cover the three main classes of synthetic biomaterial that undergo biodegradation process in vivo and have been utilized in scaffold fabrication. These are namely bioceramics (e.g., calcium phosphate compounds), polymers (e.g., aliphatic polyesters) and biometals (e.g., magnesium alloys). For each class of biomaterials, details will be provided on the degradation mechanism and the specific factors that influence degradation, including microstructural/compositional features of the biomaterials itself, as well as environmental factors. Degradation evaluation methods will be considered including both in vitro and in vivo methodologies.

AbstractObjectivesOsteoporotic fractures tend to be more challenging than fractures in healthy bone and the efficacy of metal screw fixation decreases with decreasing bone mineral density making it more difficult for such screws to gain purchase. This leads to increased complication rates such as malunion, non-union and implant failure (1). Bioresorbable polymer devices have seen clinical success in fracture fixation and are a promising alternative for metallic devices but are rarely used in the osteoporotic population. To address this, we are developing a system that may allow osteoporotic patients to avail of bioresorbable devices (2) but it is important to establish if patients have any reservations about having a plastic resorbable device instead of a metal one. Therefore the aim of this study was to explore the acceptability of bioresorbable fracture fixation devices to people with osteoporosis.MethodsA cross sectional descriptive study was conducted in a UK wide population using convenience sampling. An online survey comprising nine survey questions and nine demographic questions was developed in Microsoft Teams and tested for face validity in a small pilot study (n=6). Following amendments and ethical approval, the survey was distributed by the Royal Osteoporosis Society on their website and social media platforms. People were invited to take part if they lived in the UK, were over 18 years old and had been diagnosed with osteoporosis. The survey was open for three weeks in May 2023. Responses were analysed using descriptive statistics.ResultsThere were 112 responses. Eight participants had not been diagnosed with osteoporosis and therefore did not meet the study criteria. Of the remaining 104, 102 were female and 2 were male and 102 were white (2 chose not to disclose their ethnicity). The majority of participants were aged 55–64 (34.6%) or 65–74 (37.5%), were college/university educated (38.5%) and had previously sustained a fragility fracture (52.9%). Only 3.9% of participants had heard of bioresorbable fracture fixation devices compared to 62.5% for metal devices. Most people were unsure if they would trust one type of device over the other (58.7%) and would ask for more information if their surgeon were to suggest using a bioresorbable device to fix their fracture (61.5%). The most commonly reported concerns were about device safety and efficacy: toxicity of the degradation products and the device breaking down too early before the fracture had healed. Two participants cited environmental concerns about increased use of plastics as a reason they would decline such a device.ConclusionsAs expected, participants had little to no knowledge of bioresorbable polymer fixation devices. In general, they were willing to be guided by their surgeon but would require supporting information on the safety and efficacy of their long-term use. The results of this study show that it will be important to have relevant and understandable information to give patients when recommending these devices as treatments to ensure and support a shared-decision approach to patient care.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

The creation of scaffolds for cartilage tissue engineering has faced significant challenges in developing constructs that can provide sufficient biomechanical support and offer suitable degradation characteristics. Ideally, such tissue-engineering techniques necessitate the fabrication of scaffolds that mirror the mechanical characteristics of the articular cartilage while degrading safely without damaging the regenerating tissues. The aim of this study was to create porous, biomechanically comparable 3D-printed scaffolds made from Poly(L-lactide-co-glycolide) 85:15 and to assess their degradation at physiological conditions 37 °C in pH 7.4 phosphate-buffered saline (PBS) for up to 56 days. Furthermore, the effect of scaffold degradation on the cell viability and proliferation of human bone marrow mesenchymal stem cells (HBMSC) was evaluated in vitro. To assess the long-term degradation of the scaffolds, accelerated degradation tests were performed at an elevated temperature of 47 °C for 28 days. The results show that the fabricated scaffolds were porous with an interconnected architecture and had comparable biomechanical properties to native cartilage. The degradative changes indicated stable degradation at physiological conditions with no significant effect on the properties of the scaffold and biocompatibility of the scaffold to HBMSC. Furthermore, the accelerated degradation tests showed consistent degradation of the scaffolds even in the long term without the notable release of acidic byproducts. It is hoped that the fabrication and degradation characteristics of this scaffold will, in the future, translate into a potential medical device for cartilage tissue regeneration.

A fracture fixation device capable of stimulating bone formation and inhibiting bone resorption is desirable for treating osteoporotic fractures. Strontium (Sr) is known to have a dual effect on bone metabolism, but its use in fracture fixation devices is still limited to date as the regulation of Sr release remains difficult. In this work, a bioresorbable device with controlled Sr release capability is fabricated by incorporating strontium carbonate (SrCO3) into a poly (lactic-co-glycolic acid) (PLGA) filament followed by surface modification using electron beam (ebeam) near-surface irradiation. The presence of SrCO3 effectively retards autocatalytic polymer degradation and improves the mechanical durability of the device. The utilization of ebeam irradiation induces controlled surface degradation of the polymer matrix and triggers the release of Sr in a predictable manner. In vitro experiment results reveal that the ebeam irradiated PLGA-SrCO3 filaments have good biocompatibility and can promote the proliferation of human foetal osteoblasts (hFOBs), making it potentially useful for improving osteoporotic fracture fixation.

Bioresorbable polymers composed of poly(D,L-lactide-co-glycolide) (PDLLGA) and poly(L-lactide-co-glycolide) (PLLGA) have become increasingly popular for the preparation of bone substitute constructs. However, there are reports of a delayed inflammatory reaction occurring months or years after implantation. Due to the long polymer degradation times, in vitro tests carried out at physiological temperature, 37°C, tend to assess only the short-term biocompatibility of these materials. The aim of this work is to develop an in vitro protocol that can be used to assess the long-term cytotoxicity of bioresorbable polymers in a time efficient manner. This study used a previously developed and validated accelerated degradation protocol to obtain samples of PDLLGA and PLLGA at increasing levels of degradation. Samples were then applied to standard ISO 10993-5 direct contact cytotoxicity testing and it was found that PDLLGA samples showed increasing levels of cytotoxicity at the later stages of degradation, with PLLGA samples demonstrating significantly less cytotoxic behaviour. Following concern that accumulation of acidic degradation products in a closed multi-well culture environment could overestimate cytotoxicity, we developed and validated a new dynamic flow culture methodology, for testing the cytotoxicity of these degradable materials, by adapting a commercial “organ on a chip” flow culture system, Quasi Vivo®. In addition to cytotoxicity testing, we have carried out profiling of inflammatory cytokines released by cells in response to degraded PDLLGA and PLLGA, and have suggested mechanism by which lactide-based bioresorbable materials could modulate the inflammatory response through the G-protein coupled receptor (GPCR), hydroxycarboxylic acid receptor 1 (HCA1).

Aim: Developing and assessing the feasibility of using a three-dimensional (3D) printed patient-specific anthropomorphic pelvis phantom for dose calculation and verification for stereotactic ablative radiation therapy (SABR) with dose escalation to the dominant intraprostatic lesions. Material and methods: A 3D-printed pelvis phantom, including bone-mimicking material, was fabricated based on the computed tomography (CT) images of a prostate cancer patient. To compare the extent to which patient and phantom body and bones overlapped, the similarity Dice coefficient was calculated. Modular cylindrical inserts were created to encapsulate radiochromic films and ionization chamber for absolute dosimetry measurements at the location of prostate and at the boost region. Gamma analysis evaluation with 2%/2mm criteria was performed to compare treatment planning system calculations and measured dose when delivering a 10 flattening filter free (FFF) SABR plan and a 10FFF boost SABR plan. Results: Dice coefficients of 0.98 and 0.91 were measured for body and bones, respectively, demonstrating agreement between patient and phantom outlines. For the boost plans the gamma analysis yielded 97.0% of pixels passing 2%/2mm criteria and these results were supported by the chamber average dose difference of 0.47 +/- 0.03%. These results were further improved when overriding the bone relative electron density: 97.3% for the 2%/2mm gamma analysis, and 0.05 +/- 0.03% for the ionization chamber average dose difference. Conclusions: The modular patient-specific 3D-printed pelvis phantom has proven to be a highly attractive and versatile tool to validate prostate SABR boost plans using multiple detectors.

The further development of future Magnesium based biodegradable implants must consider not only the freedom of design, but also comprise implant volume reduction, as both aspects are crucial for the development of higher functionalised implants, such as plate systems or scaffold grafts in bone replacement therapy. As conventional manufacturing methods such as turning and milling are often accompanied by limitations concerning implant design and functionality, the process of laser powder bed fusion (LPBF) specifically for Magnesium alloys was recently introduced. In addition, the control of the degradation rate remains a key aspect regarding biodegradable implants. Recent studies focusing on the degradation behaviour of additively manufactured Magnesium scaffolds disclosed additional intricacies when compared to conventionally manufactured Magnesium parts, as a notably larger surface area was exposed to the immersion medium and scaffold struts degraded non-uniformly. Moreover, chemical etching as post processing technique is applied to remove sintered powder particles from the surface, altering surface chemistry. In this study, cylindrical Magnesium specimens were manufactured by LPBF and surfaces were consecutively modified by phosphoric etching and machining. Degradation behaviour and biocompatibility were then investigated, revealing that etched samples exhibited the overall lowest degradation rates, but experienced large pit formation, while the reduction of surface roughness resulted in a delay of degradation.

Binder jetting additive manufacturing (AM) is a promising process to print hydroxyapatite (HA) powder into bone tissue implants. However, one challenge remaining is the poor reactivity between HA powder with standard water-based ink. This study investigated different water-soluble adhesives to increase the 3D printability of HA powder. Maltodextrin and polyvinyl alcohol (PVOH) with low and high molecular weight (MW) were blended with HA from 10 to 30 wt%. Powder characterisation and evaluation of the compressive properties and geometrical accuracy of the 3D printed scaffolds were performed to identify the optimal adhesive powder. This study adopted an image registration technique to quantify the geometrical accuracy of the final 3D printed scaffold in a more comprehensive and representative way than conventionally dimensional measurement. With these approaches, a highly promising binder jetting formulation has been developed via mixing HA powder with 30 wt% PVOH (high MW). Samples manufactured from this formulation successfully achieved a geometrical accuracy greater than 85% and an excellent green compressive strength of 5.63 +/- 0.27 MPa, which was 500% higher than the commercial binder jetting powder. This is the first study to demonstrate a high level of printability when using a formulation containing >= 70 wt% HA powder and a water-based binder in the binder jetting AM process. Using the optimal powder composition developed in this study could potentially improve the structural, mechanical, and biological performances of HA-based 3D scaffolds manufactured using the binder jetting AM process for bone tissue engineering applications.

Processing tubes from poly (l-lactic acid) (PLLA) by stretch blow moulding (SBM) is used in the manufacture of bioresorbable vascular scaffolds (BVS) to improve their mechanical performance. To better understand this processing technique, a novel experimental setup by free stretch blow inside a water bath was developed to visualise the tube forming process and analyse the deformation behaviour. PLLA tubes were heated, stretched and blown with no mould present inside a temperature-controlled water bath whilst recording the processing parameters (axial force, inflation pressure). The onset of pressure activation relative to the axial stretch was controlled deliberately to produce a simultaneous (SIM) or sequential (SEQ) mode of deformation. Real-time images of the tube during forming were captured using high speed cameras and the surface strain of the patterned tube was extracted using digital image correlation (DIC). The deformation characteristics of PLLA tubes in SBM was quantified by analysis of shape evolution, strain history and stress-strain relationship.

Medical devices destined for insertion into the body must be sterilised before implantation to prevent infection or other complications. Emerging biomaterials, for example bioresorbable polymers, can experience changes in their properties due to standard industrial sterilization processes. Gamma irradiation is one of the most reliable, large scale sterilization methods, however it can induce chain scission, cross-linking or oxidation reactions in polymers. sterilization at low temperature or in an inert atmosphere has been reported to reduce the negative effects of gamma irradiation. The aim of this study was to investigate the impact of low temperature sterilization (at −80°C) when compared to sterilization at ambient temperature (25°C) both in inert atmospheric conditions of nitrogen gas, on poly(lactide co-glycolide) (PLGA).PLGA was irradiated at −80 and 25°C at 40kGy in a nitrogen atmosphere. Samples were characterised using differential scanning calorimetry (DSC), tensile test, Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC).The results showed that the molecular weight was significantly reduced as was the glass transition temperature, an indication of chain scission. FTIR showed small changes in chemical structure in the methyl and carbonyl groups after irradiation. Glass transition temperature was significantly different between irradiation at −80°C and irradiation at 25°C, however this was a difference of only 1°C. Ultimately, the results indicate that the sterilization temperature used does not affect PLGA when carried out in a nitrogen atmosphere.

Diatoms are unicellular microalgae whose cell walls are composed of remarkably uniform, hierarchical micro/nanopatterned, amorphous biosilica that cannot be replicated synthetically. Each species h...

Determination of the dispersion characteristics/or morphology of additives in polymer melts by fast, reliable and accurate on-line methods is highly desired in the polymer industry. An ultraviolet-visible (UV-Vis) spectroscopic methodology is described which meets these demands. It is demonstrated that the applied methodology may be developed on a cheap, packaging grade of Polylactic Acid (PLLA), an important bioresorbable polymer for the medical device industry, and still be accurate when implemented on a production line using a more expensive (medical) grade of the polymer compound. Simple chemometric algorithms are applied allowing the data processing step to be carried out in near real time, thus providing vital information to process operators which allows any out of control process to be identified and rectified without product loss.

In this study, bone tissue engineered scaffolds fabricated via powder-based 3D printing from hydroxyapatite (HA) and calcium sulphate (CaSO4) powders were investigated. The combination of using a fast resorbing CaSO4 based powder and the relatively slower HA powder represents a promising prospect for tuning the bioresorption of 3D printed (3DP) scaffolds. These properties could then be tailored to coincide with tissue growth rate for different surgical procedures. The manufactured scaffolds were infiltrated with poly(ε‑caprolactone) (PCL). The PCL infiltrated the inter-particle spacing within the 3DP structures due to the nature of a loosely-packed powder bed and also covered the surface of ceramic-based scaffolds. Consequently, the average compressive strength, compressive modulus and toughness increased by 314%, 465% and 867%, respectively. The resorption behaviour of the 3DP scaffolds was characterised in vitro using a high-throughput system that mimicked the physiological environment and dynamic flow conditions relevant to the human body. A rapid release of CaSO4 between Day 0 and 28 was commensurate with a reduction in scaffold mass and compressive properties, as well as an increase in medium absorption. In spite of this, HA particles, connected by PCL fibrils, remained within the microstructure after 56 days resorption under dynamic conditions. Consequently, a high level of structural integrity was maintained within the 3DP scaffold. This study presented a porous PCL-HA-CaSO4 3DP structure with the potential to encourage new tissue growth during the initial stages of implantation and also offering sufficient structural and mechanical support during the bone healing phase.

Stretch blow moulding in manufacturing bioresorbable vascular scaffold (BVS) from poly (l-lactic acid) (PLLA) provides a biaxial deformation process of raw materials to enhance the mechanical performance. Current knowledge on the mechanical behaviour of PLLA materials in this deformation process is still lacked and trial-and-error tests are relied to develop a successful operation, causing significant waste of material and cost. Motivated by this circumstance, mechanical properties of PLLA materials were investigated by biaxial stretching test at designed strain history mimicking the stretch blow moulding process. A nonlinear viscoelastic material model, i.e. Glass-rubber model was calibrated based on the experimental data from equal biaxial (EB) and constant-width (CW) stretching tests. Material anisotropy was implemented into the original model by introducing the initial orientation factor from the extrusion process. Biaxial deformation process of PLLA materials under variable strain history was modelled by the calibrated and modified model. Modelling results exhibited good agreement with the experimental data, highlighting the potential application of material modelling in improving the understanding on stretch blow moulding of PLLA materials in the industrial manufacture.

Coccolithophores are unicellular marine phytoplankton, which produce intricate, tightly regulated, exoskeleton calcite structures. The formation of biogenic calcite occurs either intracellularly, forming 'wheel-like' calcite plates, or extracellularly, forming 'tiled-like' plates known as coccoliths. Secreted coccoliths then self-assemble into multiple layers to form the coccosphere, creating a protective wall around the organism. The cell wall hosts a variety of unique species-specific inorganic morphologies that cannot be replicated synthetically. Although biomineralisation has been extensively studied, it is still not fully understood. It is becoming more apparent that biologically controlled mineralisation is still an elusive goal. A key question to address is how nature goes from basic building blocks to the ultrafine, highly organised structures found in coccolithophores. A better understanding of coccolithophore biomineralisation will offer new insight into biomimetic and bioinspired synthesis of advanced, functionalised materials for bone tissue regeneration. The purpose of this review is to spark new interest in biomineralisation and gain new insight into coccolithophores from a material science perspective, drawing on existing knowledge from taxonomists, geologists, palaeontologists and phycologists.