Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.

The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.

Can placement of hook at the upper instrumented level decrease the proximal junctional kyphosis risk in adolescent idiopathic scoliosis?

OBJECTIVE: Proximal junctional kyphosis is a commonly encountered clinical and radiographic phenomenon after pediatric and adolescent spinal deformity surgery that may lead to postoperative deformity, pain, and dissatisfaction. The purpose of the study was to identify whether the placement of transverse process hooks is an effective way to prevent PJK. METHODS: Adolescent idiopathic scoliosis patients who underwent posterior spinal fusion between November 2015 and May 2019 were retrospectively analyzed. A minimum 2-year follow-up was required. Demographic and surgical data included UIV level type of instrumentation (hook vs screw) were reported. Radiologic parameters included main curve Cobb angle, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), and proximal junctional angle (PJA) were assessed. Patients were divided into two groups based on the type of instrumentation at the UIV level whether placement of hook versus pedicle screw. RESULTS: Three hundred and thirty-seven patients were included with the mean age 14.2 ± 1.9 years. Thirty patients (8.9%) were diagnosed with proximal junctional kyphosis radiographically. PJK incidence was found 3.2% (5/154) in the hook group and 13.3% (23/172) in the screw group and the difference found statistically significant. In the PJK group, preoperative thoracic kyphosis and the degree of kyphosis correction were also significantly higher than non-PJK patients. CONCLUSION: Placement of transverse process hooks at the UIV level in posterior spinal fusion surgery for AIS patients was associated with decreased risk of PJK. A larger preoperative kyphosis and greater degree of kyphosis correction correlated with PJK.

Osseointegration reduces aseptic loosening of primary distal femoral implants in pediatric and adolescent osteosarcoma patients: a retrospective clinical and radiographic study.

AIM: The challenge of distal femoral replacement (DFR) longevity remains a priority for orthopaedic oncologists as the overall survival and activity level of young patients with osteosarcoma continues to improve. This study hypothesized that increased extracortical osseointegration at the bone-implant shoulder (i.e., where the metal implant shaft abuts the femur) will improve stress transfer adjacent to the implant, as evidenced by reduced cortical bone loss, radiolucent line progression and implant failure in young patients (< 20 years) following DFR surgery. METHODS: Twenty-nine patients of mean age 13.09 ± 0.56 years received a primary DFR. The clinical outcome of 11 CPS®, 10 GMRS®, 5 Stanmore® and 3 Repiphysis® implants was evaluated over a mean follow-up period of 4.25 ± 0.55 years. The osseous response to a bone-implant shoulder composed of either a hydroxyapatite-coated grooved ingrowth collar (Stanmore®), a porous metal coating (GMRS®) or a polished metal surface (Repiphysis®) was quantified radiographically. RESULTS: All (100.0%) of the Stanmore® implants, 90.0% of GMRS®, 81.8% of CPS® and 33.3% of the Repiphysis® implants survived. Significantly increased extracortical bone and osseointegration were measured adjacent to the Stanmore® bone-implant shoulder when compared with the GMRS® and Repiphysis® implants (p < 0.0001 in both cases). Significantly decreased cortical loss was identified in the Stanmore® group (p = 0.005, GMRS® and p < 0.0001, Repiphysis®) and at 3 years, the progression of radiolucent lines adjacent to the intramedullarly stem was reduced when compared with the GMRS® and Repiphysis® implants (p = 0.012 and 0.026, respectively). CONCLUSIONS: Implants designed to augment osseointegration at the bone-implant shoulder may be critical in reducing short- (≤ 2 years) to mid- (≤ 5 years) term aseptic loosening in this vulnerable DFR patient group. Further longer-term studies are required to confirm these preliminary findings.

Antimicrobial photodynamic therapy-a promising treatment for prosthetic joint infections.

Periprosthetic joint infection (PJI) is associated with high patient morbidity and a large financial cost. This study investigated Photodynamic Therapy (PDT) as a means of eradicating bacteria that cause PJI, using a laser with a 665-nm wavelength and methylene blue (MB) as the photosensitizer. The effectiveness of MB concentration on the growth inhibition of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Pseudomonas aeruginosa and Acinetobacter baumannii was investigated. The effect of laser dose was also investigated and the optimized PDT method was used to investigate its bactericidal effect on species within planktonic culture and following the formation of a biofilm on polished titanium and hydroxyapatite coated titanium discs. Results showed that Staphylococci were eradicated at the lowest concentration of 0.1 mM methylene blue (MB). With P. aeruginosa and A. baumannii, increasing the MB concentration improved the bactericidal effect. When the laser dose was increased, results showed that the higher the power of the laser the more bacteria were eradicated with a laser power ≥ 35 J/cm2 and an irradiance of 35 mW/cm2, eradicating all S. epidermidis. The optimized PDT method had a significant bactericidal effect against planktonic MRSA and S. epidermidis compared to MB alone, laser alone, or control (no treatment). When biofilms were formed, PDT treatment had a significantly higher bactericidal effect than MB alone and laser alone for all species of bacteria investigated on the polished disc surfaces. P. aeruginosa grown in a biofilm was shown to be less sensitive to PDT when compared to Staphylococci, and a HA-coated surface reduced the effectiveness of PDT. This study demonstrated that PDT is effective for killing bacteria that cause PJI.

An In Vitro Comparison of the Primary Stability of 2 Tapered Fluted Femoral Stem Designs.

BACKGROUND: Proximal bony deficiencies present a biomechanical challenge to achieving primary stability in revision hip arthroplasty. Long tapered fluted stems have been engineered to span these defects but concerns of early subsidence are well documented. This work aimed primarily to investigate the issue of subsidence with this design using a cadaveric model. A secondary aim was to compare the stability of 2 versions of this design. METHODS: Seven pairs of cadaveric femora were obtained, dual emission x-ray absorpitometry scanned, with calibration radiographs taken for digital templating. Each bone was potted according to the ISO standard for fatigue testing and a Paprosky type 3 defect was simulated. The established cone-conical Restoration Modular (Stryker) system and a novel design with a chamfered tip and flute configuration (Redapt, Smith & Nephew) were examined. Movement at the stem-bone interface was measured using radiostereometric analysis and micromotion transducers. RESULTS: All restoration stems and 85% of the Redapt stems achieved stability by recognized criteria, micromotion < 150 µm and migration less than 2 mm. A Fisher exact test comparing the proportion of stems which were stable or unstable was not significant, P = .055. Mean axial subsidence (SD) was 0.17 mm (0.32) and 0.1 mm (0.131) for the Restoration and Redapt stems respectively. CONCLUSION: This study has demonstrated minimal subsidence in the immediate post-operative period using tapered fluted stems. Both designs achieved excellent stability despite simulation of Paprosky type 3 bony defects in the cadaveric model. This geometry appears satisfactory for use in revision surgery in the presence of significant proximal bony deficiencies.

Hydroxyapatite-coated collars reduce radiolucent line progression in cemented distal femoral bone tumor implants.

BACKGROUND: Aseptic loosening of massive bone tumor implants is a major cause of prosthesis failure. Evidence suggests that an osteointegrated hydroxyapatite (HA)-coated collar would reduce the incidence of aseptic loosening around the cemented intramedullary stem in distal femoral bone tumor prostheses. Because these implants often are used in young patients with a tumor, such treatment might extend the longevity of tumor implants. Questions/purposes We asked whether (1) HA-coated collars were more likely to osteointegrate; (2) HA collars were associated with fewer progressive radiolucent lines around the stem-cement interface; and (3) HA-coated collars were associated with less bone loss at the bone-shoulder implant junction? METHODS: Twenty-two patients were pair-matched to one of two groups--either (1) implants with a HA-coated ingrowth collar (HA Collar Group); or (2) implants without an ingrowth collar (Noncollar Group). Age, sex, and length of followup were similar in both groups. HA-coated collars were developed and used at our institution from 1992 to address the high failure rate attributable to aseptic loosening in patients with massive bone tumor implants. Before this, smooth titanium shafts were used routinely adjacent to bone at the transection site. The minimum followup was 2 years (mean, 7 years; range, 2-12 years). Radiographs obtained throughout the followup period were analyzed and osteointegration at the shaft of the implant quantified. Radiolucent line progression around the cemented stem was semi-quantitatively assessed and cortical bone loss at the bone-shoulder implant junction was measured during the followup period. RESULTS: Comparison of the most recent radiographs showed nine of 11 patients had osteointegrated HA collars, whereas only one patient in the Noncollar Group had osteointegration (p > 0.001). The radiolucent line score quantified around the cemented stem was lower in the HA Collar Group when compared with the Noncollar Group (p = 0.001). Results showed an increase in cortical bone loss at the bone-shoulder implant junction in the Noncollar Group when compared with the HA Collar Group (p < 0.001). CONCLUSIONS: Osteointegration at the implant collar resulted in fewer radiolucent lines adjacent to the intramedullary cemented stem and decreased cortical bone loss immediately adjacent to the transection site. These results suggest that the HA collar may help reduce the risk of aseptic loosening in patients with this type of implant, but longer followup and a larger prospective comparison series are necessary to prove this more definitively.

Antibacterial sponge for rapid noncompressible hemostatic treatment: spatiotemporal studies using a noninvasive model.

Hemorrhage is one of the leading causes of preventable death. While minor injuries can be treated mainly by conventional methods, deep and irregular wounds with profuse bleeding present significant challenges, some of which can be life-threatening and fatal. This underscores the need to develop easily applicable FDA-approved hemostatic treatments that can effectively stanch blood loss at the point of care before professional medical care. A silicone-based bandage system (SilFoam), a non-compressible, self-expanding, antibacterial hemostatic treatment, is reported here. Its two-component system reacts in situ upon mixing to form a stretchable sponge that acts as a 'tamponade' by expanding within seconds with the evolution of oxygen gas from the interaction of the reactive components present in the formulation. This generates autogenous pressure on the wound that can effectively arrest heavy bleeding within minutes. Possessing optimal adhesive properties, the expanded sponge can be easily removed, rendering it optimal for hemostatic wound dressing. With recent advances in biotechnological research, there is a growing awareness of the potential issues associated with in vivo trials, spanning ethical, psychological, economic, and physiological concerns like burnout and fatigue. Bearing this in mind, a unique manikin system simulating a deep abdominal wound has been employed to investigate SilFoam's hemostatic efficacy with different blood-flow rates using a non-invasive model that aims to provide an easy, fast, and economical route to test hemostatic treatments before in vivo studies. This is the first time an Ag2O-based oxygen-induced foaming system has been reported as a hemostatic agent.

Surface Chemistry of Biologically Active Reducible Oxide Nanozymes.

Reducible metal oxide nanozymes (rNZs) are a subject of intense recent interest due to their catalytic nature, ease of synthesis, and complex surface character. Such materials contain surface sites which facilitate enzyme-mimetic reactions via substrate coordination and redox cycling. Further, these surface reactive sites are shown to be highly sensitive to stresses within the nanomaterial lattice, the physicochemical environment, and to processing conditions occurring as part of their syntheses. When administered in vivo, a complex protein corona binds to the surface, redefining its biological identity and subsequent interactions within the biological system. Catalytic activities of rNZs each deliver a differing impact on protein corona formation, its composition, and in turn, their recognition, and internalization by host cells. Improving the understanding of the precise principles that dominate rNZ surface-biomolecule adsorption raises the question of whether designer rNZs can be engineered to prevent corona formation, or indeed to produce "custom" protein coronas applied either in vitro, and preadministration, or formed immediately upon their exposure to body fluids. Here, fundamental surface chemistry processes and their implications in rNZ material performance are considered. In particular, material structures which inform component adsorption from the application environment, including substrates for enzyme-mimetic reactions are discussed.

Emerging Medical Technologies and Their Use in Bionic Repair and Human Augmentation.

As both the proportion of older people and the length of life increases globally, a rise in age-related degenerative diseases, disability, and prolonged dependency is projected. However, more sophisticated biomedical materials, as well as an improved understanding of human disease, is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease as well as impact disease prevention. Another, albeit quieter, revolution is also taking place within society: human augmentation. In this context, humans seek to improve themselves, metamorphosing through self-discipline or more recently, through use of emerging medical technologies, with the goal of transcending aging and mortality. In this review, and in the pursuit of improved medical care following aging, disease, disability, or injury, we first highlight cutting-edge and emerging materials-based neuroprosthetic technologies designed to restore limb or organ function. We highlight the potential for these technologies to be utilized to augment human performance beyond the range of natural performance. We discuss and explore the growing social movement of human augmentation and the idea that it is possible and desirable to use emerging technologies to push the boundaries of what it means to be a healthy human into the realm of superhuman performance and intelligence. This potential future capability is contrasted with limitations in the right-to-repair legislation, which may create challenges for patients. Now is the time for continued discussion of the ethical strategies for research, implementation, and long-term device sustainability or repair.

Multifunctional scaffolds for bone repair following age-related biological decline: Promising prospects for smart biomaterial-driven technologies.

The repair of large bone defects due to trauma, disease, and infection can be exceptionally challenging in the elderly. Despite best clinical practice, bone regeneration within contemporary, surgically implanted synthetic scaffolds is often problematic, inconsistent, and insufficient where additional osteobiological support is required to restore bone. Emergent smart multifunctional biomaterials may drive important and dynamic cellular crosstalk that directly targets, signals, stimulates, and promotes an innate bone repair response following age-related biological decline and when in the presence of disease or infection. However, their role remains largely undetermined. By highlighting their mechanism/s and mode/s of action, this review spotlights smart technologies that favorably align in their conceivable ability to directly target and enhance bone repair and thus are highly promising for future discovery for use in the elderly. The four degrees of interactive scaffold smartness are presented, with a focus on bioactive, bioresponsive, and the yet-to-be-developed autonomous scaffold activity. Further, cell- and biomolecular-assisted approaches were excluded, allowing for contemporary examination of the capabilities, demands, vision, and future requisites of next-generation biomaterial-induced technologies only. Data strongly supports that smart scaffolds hold significant promise in the promotion of bone repair in patients with a reduced osteobiological response. Importantly, many techniques have yet to be tested in preclinical models of aging. Thus, greater clarity on their proficiency to counteract the many unresolved challenges within the scope of aging bone is highly warranted and is arguably the next frontier in the field. This review demonstrates that the use of multifunctional smart synthetic scaffolds with an engineered strategy to circumvent the biological insufficiencies associated with aging bone is a viable route for achieving next-generation therapeutic success in the elderly population.

Extracellular Proteins Isolated from L. acidophilus as an Osteomicrobiological Therapeutic Agent to Reduce Pathogenic Biofilm Formation, Regulate Chronic Inflammation, and Augment Bone Formation In Vitro.

Periprosthetic joint infection (PJI) is a challenging complication that can occur following joint replacement surgery. Efficacious strategies to prevent and treat PJI and its recurrence remain elusive. Commensal bacteria within the gut convey beneficial effects through a defense strategy named "colonization resistance" thereby preventing pathogenic infection along the intestinal surface. This blueprint may be applicable to PJI. The aim is to investigate Lactobacillus acidophilus spp. and their isolated extracellular-derived proteins (LaEPs) on PJI-relevant Staphylococcus aureus, methicillin-resistant S. aureus, and Escherichia coli planktonic growth and biofilm formation in vitro. The effect of LaEPs on cultured macrophages and osteogenic, and adipogenic human bone marrow-derived mesenchymal stem cell differentiation is analyzed. Data show electrostatically-induced probiotic-pathogen species co-aggregation and pathogenic growth inhibition together with LaEP-induced biofilm prevention. LaEPs prime macrophages for enhanced microbial phagocytosis via cathepsin K, reduce lipopolysaccharide-induced DNA damage and receptor activator nuclear factor-kappa B ligand expression, and promote a reparative M2 macrophage morphology under chronic inflammatory conditions. LaEPs also significantly augment bone deposition while abating adipogenesis thus holding promise as a potential multimodal therapeutic strategy. Proteomic analyses highlight high abundance of lysyl endopeptidase, and urocanate reductase. Further, in vivo analyses are warranted to elucidate their role in the prevention and treatment of PJIs.

A neoteric antibacterial ceria-silver nanozyme for abiotic surfaces.

Community-associated and hospital-acquired infections caused by bacteria continue to yield major global challenges to human health. Bacterial contamination on abiotic surfaces is largely spread via high-touch surfaces and contemporary standard disinfection practices show limited efficacy, resulting in unsatisfactory therapeutic outcomes. New strategies that offer non-specific and broad protection are urgently needed. Herein, we report our novel ceria-silver nanozyme engineered at a molar ratio of 5:1 and with a higher trivalent (Ce3+) surface fraction. Our results reveal potent levels of surface catalytic activity on both wet and dry surfaces, with rapid, and complete eradication of Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin resistant S. aureus, in both planktonic and biofilm form. Preferential electrostatic adherence of anionic bacteria to the cationic nanozyme surface leads to a catastrophic loss in both aerobic and anaerobic respiration, DNA damage, osmodysregulation, and finally, programmed bacterial lysis. Our data reveal several unique mechanistic avenues of synergistic ceria-Ag efficacy. Ag potentially increases the presence of Ce3+ sites at the ceria-Ag interface, thereby facilitating the formation of harmful H2O2, followed by likely permeation across the cell wall. Further, a weakened Ag-induced Ce-O bond may drive electron transfer from the Ec band to O2, thereby further facilitating the selective reduction of O2 toward H2O2 formation. Ag destabilizes the surface adsorption of molecular H2O2, potentially leading to higher concentrations of free H2O2 adjacent to bacteria. To this end, our results show that H2O2 and/or NO/NO2-/NO3- are the key liberators of antibacterial activity, with a limited immediate role being offered by nanozyme-induced ROS including O2•- and OH•, and likely other light-activated radicals. A mini-pilot proof-of-concept study performed in a pediatric dental clinic setting confirms residual, and continual nanozyme antibacterial efficacy over a 28-day period. These findings open a new approach to alleviate infections caused by bacteria for use on high-touch hard surfaces.

A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis.

By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)-induced osteoporosis. Results confirm OVX-induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole-body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor-BB and leukemia inhibitory factor, with downregulation of interleukin-1 R6, and receptor activator of nuclear factor kappa-B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor-beta/SMAD, and Wingless-related integration site/be-catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo-osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX-induced bone loss.

3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration.

The fabrication of customized implants by additive manufacturing has allowed continued development of the personalized medicine field. Herein, a 3D-printed bioabsorbable poly (lactic acid) (PLA)- ß-tricalcium phosphate (TCP) (10 wt %) composite has been modified with CeO2 nanoparticles (CeNPs) (1, 5 and 10 wt %) for bone repair. The filaments were prepared by melt extrusion and used to print porous scaffolds. The nanocomposite scaffolds possessed precise structure with fine print resolution, a homogenous distribution of TCP and CeNP components, and mechanical properties appropriate for bone tissue engineering applications. Cell proliferation assays using osteoblast cultures confirmed the cytocompatibility of the composites. In addition, the presence of CeNPs enhanced the proliferation and differentiation of mesenchymal stem cells; thereby, increasing alkaline phosphatase (ALP) activity, calcium deposition and bone-related gene expression. Results from this study have shown that the 3D printed PLA-TCP-10%CeO2 composite scaffold could be used as an alternative polymeric implant for bone tissue engineering applications: avoiding additional/revision surgeries and accelerating the regenerative process.

Effect of Porosity and Pore Shape on the Mechanical and Biological Properties of Additively Manufactured Bone Scaffolds.

This study investigates the effect of porosity and pore shape on the biological and mechanical behavior of additively manufactured scaffolds for bone tissue engineering (BTE). Polylactic acid scaffolds with varying porosity levels (15-78%) and pore shapes, including regular (rectangular pores), gyroid, and diamond (triply periodic minimal surfaces) structures, are fabricated by fused filament fabrication. Murine-derived macrophages and human bone marrow-derived mesenchymal stromal cells (hBMSCs) are seeded onto the scaffolds. The compressive behavior and surface morphology of the scaffolds are characterized. The results show that scaffolds with 15%, 30%, and 45% porosity display the highest rate of macrophage and hBMSC growth. Gyroid and diamond scaffolds exhibit a higher rate of macrophage proliferation, while diamond scaffolds exhibit a higher rate of hBMSC proliferation. Additionally, gyroid and diamond scaffolds exhibit better compressive behavior compared to regular scaffolds. Of particular note, diamond scaffolds have the highest compressive modulus and strength. Surface morphology characterization indicates that the surface roughness of diamond and gyroid scaffolds is greater than that of regular scaffolds at the same porosity level, which is beneficial for cell attachment and proliferation. This study provides valuable insights into porosity and pore shape selection for additively manufactured scaffolds in BTE.

Promising applications of D-amino acids in periprosthetic joint infection.

Due to the rise in our aging population, a disproportionate demand for total joint arthroplasty (TJA) in the elderly is forecast. Periprosthetic joint infection (PJI) represents one of the most challenging complications that can occur following TJA, and as the number of primary and revision TJAs continues to rise, an increasing PJI burden is projected. Despite advances in operating room sterility, antiseptic protocols, and surgical techniques, approaches to prevent and treat PJI remain difficult, primarily due to the formation of microbial biofilms. This difficulty motivates researchers to continue searching for an effective antimicrobial strategy. The dextrorotatory-isoforms of amino acids (D-AAs) are essential components of peptidoglycan within the bacterial cell wall, providing strength and structural integrity in a diverse range of species. Among many tasks, D-AAs regulate cell morphology, spore germination, and bacterial survival, evasion, subversion, and adhesion in the host immune system. When administered exogenously, accumulating data have demonstrated that D-AAs play a pivotal role against bacterial adhesion to abiotic surfaces and subsequent biofilm formation; furthermore, D-AAs have substantial efficacy in promoting biofilm disassembly. This presents D-AAs as promising and novel targets for future therapeutic approaches. Despite their emerging antibacterial efficacy, their role in disrupting PJI biofilm formation, the disassembly of established TJA biofilm, and the host bone tissue response remains largely unexplored. This review aims to examine the role of D-AAs in the context of TJAs. Data to date suggest that D-AA bioengineering may serve as a promising future strategy in the prevention and treatment of PJI.

Nanotechnology enabled radioprotectants to reduce space radiation-induced reactive oxidative species.

Interest in space exploration has seen substantial growth following recent launch and operation of modern space technologies. In particular, the possibility of travel beyond low earth orbit is seeing sustained support. However, future deep space travel requires addressing health concerns for crews under continuous, longer-term exposure to adverse environmental conditions. Among these challenges, radiation-induced health issues are a major concern. Their potential to induce chronic illness is further potentiated by the microgravity environment. While investigations into the physiological effects of space radiation are still under investigation, studies on model ionizing radiation conditions, in earth and micro-gravity conditions, can provide needed insight into relevant processes. Substantial formation of high, sustained reactive oxygen species (ROS) evolution during radiation exposure is a clear threat to physiological health of space travelers, producing indirect damage to various cell structures and requiring therapeutic address. Radioprotection toward the skeletal system components is essential to astronaut health, due to the high radio-absorption cross-section of bone mineral and local hematopoiesis. Nanotechnology can potentially function as radioprotectant and radiomitigating agents toward ROS and direct radiation damage. Nanoparticle compositions such as gold, silver, platinum, carbon-based materials, silica, transition metal dichalcogenides, and ceria have all shown potential as viable radioprotectants to mitigate space radiation effects with nanoceria further showing the ability to protect genetic material from oxidative damage in several studies. As research into space radiation-induced health problems develops, this review intends to provide insights into the nanomaterial design to ameliorate pathological effects from ionizing radiation exposure. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Nanotechnology Approaches to Biology > Cells at the Nanoscale Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Inorganic Nanoparticles as Radiosensitizers for Cancer Treatment.

Nanotechnology has expanded what can be achieved in our approach to cancer treatment. The ability to produce and engineer functional nanoparticle formulations to elicit higher incidences of tumor cell radiolysis has resulted in substantial improvements in cancer cell eradication while also permitting multi-modal biomedical functionalities. These radiosensitive nanomaterials utilize material characteristics, such as radio-blocking/absorbing high-Z atomic number elements, to mediate localized effects from therapeutic irradiation. These materials thereby allow subsequent scattered or emitted radiation to produce direct (e.g., damage to genetic materials) or indirect (e.g., protein oxidation, reactive oxygen species formation) damage to tumor cells. Using nanomaterials that activate under certain physiologic conditions, such as the tumor microenvironment, can selectively target tumor cells. These characteristics, combined with biological interactions that can target the tumor environment, allow for localized radio-sensitization while mitigating damage to healthy cells. This review explores the various nanomaterial formulations utilized in cancer radiosensitivity research. Emphasis on inorganic nanomaterials showcases the specific material characteristics that enable higher incidences of radiation while ensuring localized cancer targeting based on tumor microenvironment activation. The aim of this review is to guide future research in cancer radiosensitization using nanomaterial formulations and to detail common approaches to its treatment, as well as their relations to commonly implemented radiotherapy techniques.

Improving disease prevention, diagnosis, and treatment using novel bionic technologies.

Increased human life expectancy, due in part to improvements in infant and childhood survival, more active lifestyles, in combination with higher patient expectations for better health outcomes, is leading to an extensive change in the number, type and manner in which health conditions are treated. Over the next decades as the global population rapidly progresses toward a super-aging society, meeting the long-term quality of care needs is forecast to present a major healthcare challenge. The goal is to ensure longer periods of good health, a sustained sense of well-being, with extended periods of activity, social engagement, and productivity. To accomplish these goals, multifunctionalized interfaces are an indispensable component of next generation medical technologies. The development of more sophisticated materials and devices as well as an improved understanding of human disease is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer's disease and will impact disease prevention. This review examines emerging cutting-edge bionic materials, devices and technologies developed to advance disease prevention, and medical care and treatment in our elderly population including developments in smart bandages, cochlear implants, and the increasing role of artificial intelligence and nanorobotics in medicine.

Ultrasound-Responsive Nanobubbles for Combined siRNA-Cerium Oxide Nanoparticle Delivery to Bone Cells.

This study aims to present an ultrasound-mediated nanobubble (NB)-based gene delivery system that could potentially be applied in the future to treat bone disorders such as osteoporosis. NBs are sensitive to ultrasound (US) and serve as a controlled-released carrier to deliver a mixture of Cathepsin K (CTSK) siRNA and cerium oxide nanoparticles (CeNPs). This platform aimed to reduce bone resorption via downregulating CTSK expression in osteoclasts and enhance bone formation via the antioxidant and osteogenic properties of CeNPs. CeNPs were synthesized and characterized using transmission electron microscopy and X-ray photoelectron spectroscopy. The mixture of CTSK siRNA and CeNPs was adsorbed to the surface of NBs using a sonication method. The release profiles of CTSK siRNA and CeNPs labeled with a fluorescent tag molecule were measured after low-intensity pulsed ultrasound (LIPUS) stimulation using fluorescent spectroscopy. The maximum release of CTSK siRNA and the CeNPs for 1 mg/mL of NB-(CTSK siRNA + CeNPs) was obtained at 2.5 nM and 1 µg/mL, respectively, 3 days after LIPUS stimulation. Then, Alizarin Red Staining (ARS) was applied to human bone marrow-derived mesenchymal stem cells (hMSC) and tartrate-resistant acid phosphatase (TRAP) staining was applied to human osteoclast precursors (OCP) to evaluate osteogenic promotion and osteoclastogenic inhibition effects. A higher mineralization and a lower number of osteoclasts were quantified for NB-(CTSK siRNA + CeNPs) versus control +RANKL with ARS (p < 0.001) and TRAP-positive staining (p < 0.01). This study provides a method for the delivery of gene silencing siRNA and CeNPs using a US-sensitive NB system that could potentially be used in vivo and in the treatment of bone fractures and disorders such as osteoporosis.