Antimicrobial and Biodegradable 3D Printed Scaffolds for Orthopedic Infections.

In bone tissue engineering, the performance of scaffolds underpins the success of the healing of bone. Microbial infection is the most challenging issue for orthopedists. The application of scaffolds for healing bone defects is prone to microbial infection. To address this challenge, scaffolds with a desirable shape and significant mechanical, physical, and biological characteristics are crucial. 3D printing of antibacterial scaffolds with suitable mechanical strength and excellent biocompatibility is an appealing strategy to surmount issues of microbial infection. The spectacular progress in developing antimicrobial scaffolds, along with beneficial mechanical and biological properties, has sparked further research for possible clinical applications. Herein, the significance of antibacterial scaffolds designed by 3D, 4D, and 5D printing technologies for bone tissue engineering is critically investigated. Materials such as antibiotics, polymers, peptides, graphene, metals/ceramics/glass, and antibacterial coatings are used to impart the antimicrobial features for the 3D scaffolds. Polymeric or metallic biodegradable and antibacterial 3D-printed scaffolds in orthopedics disclose exceptional mechanical and degradation behavior, biocompatibility, osteogenesis, and long-term antibacterial efficiency. The commercialization aspect of antibacterial 3D-printed scaffolds and technical challenges are also discussed briefly. Finally, the discussion on the unmet demands and prevailing challenges for ideal scaffold materials for fighting against bone infections is included along with a highlight of emerging strategies in this field.

Biotribological behaviour, biodegradability and osteocompatibility of Mg-3Zn/HA composite based intramedullary inserts in avian model.

Bioactivity, structural integrity and tribological behaviour of biodegradable orthopaedic fracture fixing accessories considerably impact their actual performance in the body environment. Immune system in the living body quickly responds to the wear debris as foreign material and begins a complex inflammatory response. Magnesium (Mg) based biodegradable implants are widely studied for temporary orthopaedic applications, due to their similar elastic modulus and density to natural bones. However, Mg is highly vulnerable to corrosion and tribological damage in actual service conditions. To address these challenges via a combined approach, the Mg-3 wt% Zinc (Zn)/x hydroxyapatite (HA, x = 0, 5 and 15 wt%) based composites (fabricated via spark plasma sintering route) are evaluated in terms of biotribocorrosion and in-vivo biodegradation and osteocompatibility behaviour in an avian model. The addition of 15 wt% HA in the Mg-3Zn matrix has significantly enhanced the wear and corrosion resistance in the physiological environment. X-ray radiograph analysis of the Mg-HA-based intramedullary inserts implanted in the humerus bone of birds showed consistent progression of degradation and positive tissue response up to 18 weeks. The 15 wt% HA reinforced composites have shown better bone regeneration properties than other inserts. This study provides new insights into developing next-generation Mg-HA-based biodegradable composites for temporary orthopaedic implants, with excellent biotribocorrosion behaviour.

Assessment of protein adhesion behaviour and biocompatibility of magnesium/Co-substituted HA-based composites for orthopaedic application.

Protein adsorption has a great influence on Mg-based metallic implants, which affects cell attachment and cell growth. Adsorption of the proteins (via electrostatic interaction, hydrophobic/hydrophilic, and hydrogen-bonding) on the implant surface is greatly influenced by the surface chemistry of the implant. Hydroxyapatite (HA) is a class of CaP ceramic, beneficial for protein adsorption as it possesses Ca2+ and PO43- in it, which are believed to be the protein binding sites on the HA surface. Moreover, HA is the popular choice for reinforcement in the magnesium matrix owing to its similarity with bone mineral composition. However, negligible interaction between HA and Mg particles during sintering is the major limitation for frequent usage of Mg-HA implants. Doping of HA with Mg2+ and Zn2+ (CoHA) ions leads to its chemistry similar to natural apatite in human bone and facilitates comparatively better bonding with the MgZn matrix. This study mainly aims to delve into the protein adsorption behaviour of Magnesium/Co-substituted HA-based Composites (M3Z-CoHA) along with their biocompatibility. Qualitative and quantitative protein adsorption analysis shows that the addition of 15 wt% CoHA to Mg matrix enhanced protein adsorption by ~60% and renders cell viability >90% after day 1, supporting cellular growth and proliferation. The implants also initiated osteogenic differentiation of the cells after day 7. The leached-out products from all the composites showed no toxicity. The morphology of the cells in all the composites was found as healthy as the control cells. Overall, the composite with 15 wt% HA reinforcement (M3Z-15CoHA) has shown favourable protein adsorption behaviour and cytocompatibility.

Promises of Functionally Graded Material in Bone Regeneration: Current Trends, Properties, and Challenges.

Functionally graded materials (FGMs) are emerging materials systems, with structures and compositions gradually changing in a particular direction. Consequently, the properties of the materials gradually change in the desired direction to achieve particular nonhomogeneous service demands without abrupting the compositional and behavioral interface at the macroscale. FGMs have been found to have high potential as orthopedic implants; because the functional gradient can be adapted in such a manner that the core of FGM should be compatible with the density and strength of bone, interlayers can maintain the structural integrity and outermost layers would provide bioactivity and corrosion resistance, thus overall tailoring the stress shielding effect. This review article discusses the typical FGM systems existing in nature and the human body, focusing on bone tissue. Further, the reason behind the application of these FGMs systems in orthopedic implants is explored in detail, considering the physical and biological necessities. The substantial focus of the present critical review is devoted to two primary topics related to the usage of FGMs for orthopedic implants: (1) the synthesizing techniques currently available to produce FGMs for load-bearing orthopedic applications and (2) the properties, such as mechanical, structural, and biological behavior of the FGMs. This review article gives an insight into the potential of FGMs for orthopedic applications.

Synthesis and evaluation of magnesium/co-precipitated hydroxyapatite based composite for biomedical application.

Owing to its inductive attributes, hydroxyapatite is an ideal reinforcement to tailor the degradation kinetics of magnesium-based temporary orthopedic implants. However, the large difference in the melting temperature of hydroxyapatite and magnesium lead to an insignificant interaction between them during the sintering process, which has been a major limitation in their consolidation. Doping of pure HA with Mg2+ and Zn2+ ions could be a viable solution by making it coherent with the Mg matrix. Further, such doping also results in a chemistry more similar to the natural apatite in human bone. In this study, Mg2+ and Zn2+ ions doped hydroxyapatite (CoHA) is synthesized and reinforced to obtain high density in Mg-based composites, fabricated through spark plasma sintering. Composite with 15 wt % CoHA offered ~113% improvement in the ultimate compressive strength. Higher relative density, due to improved consolidation, might be the reason for higher mechanical strength. Hydrogen evolution (up to 64 h) and static immersion studies (up to 28 days) revealed comparatively higher corrosion resistance for 10 wt% CoHA composites. This study gives insight into the potential of fabrication and designing of the M3Z-CoHA composites for temporary orthopedic implants.

Biocompatibility and biodegradability evaluation of magnesium-based intramedullary bone implants in avian model.

At present days osteosynthesis modalities for avian fracture management are inadequate. External coaptation is the most practiced method however, specialized clinics have started introducing intramedullary pinning, external skeletal fixation with tie-in-fixation for fracture immobilization. Magnesium (Mg) based biomaterials are trustable developments in the field of orthopedics compared to their permanent stainless steel counterparts concerning long term adverse reaction. Mg implants are becoming promising for their use as intramedullary accessories because they are bioresorbable with high strength-weight ratio and the similarities in density and elastic modulus to the natural bones. However, their severe biodegradation trait restricts frequent use as load-bearing orthopedic implants. In this study, the biocompatibility and biodegradability of Mg based intramedullary cylindrical spacers (2.4 mm diameter × 8 mm height) reinforced with 0, 5, 15 wt% of hydroxyapatite (HA, Ca10 (PO4 )6 (OH)2 ) were evaluated in 18 Uttara-fowl birds. Clinical, radiological (from immediate postoperative days till 24th week), biochemical (first three postoperative weeks) and histopathological study of test bone were carried out to evaluate implant degradation and osteocompatibility. Biodegradation of Mg-3Zn/0HA and Mg-3Zn/15HA initiated a bit earlier at second week of implantation, while that of Mg-3Zn/5HA at 3-fourth week, and found biocompatible and biodegradable with no observable clinical and histopathological changes.

Functionally gradient magnesium-based composite for temporary orthopaedic implant with improved corrosion resistance and osteogenic properties.

Magnesium (Mg) is a potential alternative for conventional orthopaedic implant materials owing to its biodegradation behavior and physical characteristics similar to natural human bone. Due to its biomimetic mechanical attributes, Mg in orthopaedic applications could reduce the risk of the 'stress shielding effect'. However, the major limitation of Mg is its high in-vivo corrosion rate. Thermal sprayed coatings of osteoconductive ceramics like hydroxyapatite (HA) have been explored as a potential solution, albeit with limited success due to the low melting point of Mg, which restricts the ease of fabricating surface-adherent ceramic coating. The present study focuses on overcoming this limitation through a Mg-HA functionally gradient material (FGM) system, which is expected to provide a highly corrosion-resistant surface and uniform mechanical integrity throughout the structure. In addition to corrosion resistance, the FGM system has improved biocompatibility and osteoconductivity without compromising its mechanical stability. The FGM, with a compositional gradient of Mg-HA composite, consisting of Mg at the core and increasing HA towards the outer layer, has been fabricated through spark plasma sintering. Mechanical properties of the overall structure were better than those of the best individual composite. More importantly, corrosion resistance of the FGM structure was significantly improved (~154%) as compared to individual composites. In addition, alkaline phosphatase activity, osteogenic gene expression and cell viability, all pertaining to efficient osteogenic differentiation, were enhanced for FGM and 15 wt% HA reinforced composites. These observations suggest that the FGM structure is promising for temporary biodegradable orthopaedic implants.

The challenges of theory-software translation.

Background: Software is now ubiquitous within research. In addition to the general challenges common to all software development projects, research software must also represent, manipulate, and provide data for complex theoretical constructs. Ensuring this process of theory-software translation is robust is essential to maintaining the integrity of the science resulting from it, and yet there has been little formal recognition or exploration of the challenges associated with it. Methods: We thematically analyse the outputs of the discussion sessions at the Theory-Software Translation Workshop 2019, where academic researchers and research software engineers from a variety of domains, and with particular expertise in high performance computing, explored the process of translating between scientific theory and software. Results: We identify a wide range of challenges to implementing scientific theory in research software and using the resulting data and models for the advancement of knowledge. We categorise these within the emergent themes of design, infrastructure, and culture, and map them to associated research questions. Conclusions: Systematically investigating how software is constructed and its outputs used within science has the potential to improve the robustness of research software and accelerate progress in its development. We propose that this issue be examined within a new research area of theory-software translation, which would aim to significantly advance both knowledge and scientific practice.

Assessment of biomechanical stability and formulation of a statistical model on magnesium based composite in two different milieus.

Magnesium (Mg) based temporary implants are an appealing new solution to counter the problems associated with the currently available temporary orthopaedic implants, used in fracture fixing. To make the extensive use of Mg-based implants in-vivo, mechanical integrity in the physiological environment is a prerequisite. This study presents an insight into the biomechanical stability of Mg-3Zn/HA (0, 5, and 15 wt % of HA) composites in two different milieus (simulated body fluid (SBF) and serum contained SBF (m-SBF)). After 14 days of static immersion in SBF, ~65% mechanical strength was compromised in the case of 15 wt % HA reinforcement. However, the degradation rate was slowed down by ~35% with the addition of 15 wt % HA in Mg-3Zn. Mg-3Zn/HA composite, when soaked in both fluids, was found to induce apatite layer formation on the surfaces for several days. However, in the case of m-SBF immersion, 15 wt % HA facilitated less precipitation of apatite growth when compared to SBF immersion. Nevertheless, m-SBF immersed 15 wt % HA composite facilitated better corrosion resistance and excellent mechanical stability after 14 days of immersion. The approach thereby assists in establishing an effective mechanism between the degradation and mechanical stability in in-vitro immersion. In addition, this study has also developed a semi-empirical model for prediction of the compressive strength of these composites as a function of the number of days of immersion and the content of hydroxyapatite (HA). This semi-empirical model will help in predicting the biomechanical stability for long-term in-vitro exposures, which might be of use in evaluating the effect of the in-vivo environment.

Exascale applications: skin in the game.

As noted in Wikipedia, skin in the game refers to having 'incurred risk by being involved in achieving a goal', where 'skin is a synecdoche for the person involved, and game is the metaphor for actions on the field of play under discussion'. For exascale applications under development in the US Department of Energy Exascale Computing Project, nothing could be more apt, with the skin being exascale applications and the game being delivering comprehensive science-based computational applications that effectively exploit exascale high-performance computing technologies to provide breakthrough modelling and simulation and data science solutions. These solutions will yield high-confidence insights and answers to the most critical problems and challenges for the USA in scientific discovery, national security, energy assurance, economic competitiveness and advanced healthcare. This article is part of a discussion meeting issue 'Numerical algorithms for high-performance computational science'.

Differential in vitro degradation and protein adhesion behaviour of spark plasma sintering fabricated magnesium-based temporary orthopaedic implant in serum and simulated body fluid.

The interaction of proteins with implantable metallic surfaces has a great influence on the bioactivity and biodegradation of orthopaedic implants. Initial osseointegration is known to be critical for the long term success of orthopaedic implants. The surface properties of the implant and electrochemical milieu of the surrounding solution such as electrostatic, hydrophobic, and hydrogen bonding interactions significantly modulate protein adsorption by implants. Magnesium (Mg) is considered to improve the adhesion of osteoblasts via ligand binding of the integrin receptors. Mg-based composites, reinforced with hydroxyapatite (HA), are potential candidates for temporary orthopaedic implants. However, their clinical translation requires enhanced degradation resistance in physiological environment so that it is in sync with the healing rate of the bone. The present study deals with the protein adsorption characteristics and degradation behaviour of Mg-HA-based biodegradable implants. Quantitative analysis of apatite inducing ability of composites was evaluated in terms of mass gain in simulated body fluid (SBF) as well as in foetal bovine serum (FBS), by an in vitro immersion study. Incorporation of 5 and 15 wt% HA to Mg-3Zn improved apatite formation up to 35% and 66%, respectively, after 14 days of immersion in SBF. Compared to FBS, SBF is found to be significantly more effective in precipitating apatite on a Mg-HA surface. However, FBS offered more corrosion resistance to Mg-HA than SBF did, as evident from the significant differences in the protein adhesion capabilities of the composite surface when incubated separately in these two mediums. The addition of 15 wt% HA enhanced the protein adsorption capability by ∼35%. These studies highlight the possibility of modulating the degradation and bioactivity of Mg-based composite by tailoring the composition of HA. These findings, in turn, warrant the suitability of Mg-HA composite in orthopaedic application.