Advances in additive manufacturing of polycaprolactone based scaffolds for bone regeneration.

Critical sized bone defects are difficult to manage and currently available clinical/surgical strategies for treatment are not completely successful. Polycaprolactone (PCL) which is a biodegradable and biocompatible thermoplastic can be 3D printed using medical images into patient specific bone implants. The excellent mechanical properties and low immunogenicity of PCL makes it an ideal biomaterial candidate for 3D printing of bone implants. Though PCL suffers from the limitation of being bio-inert. Here we describe the use of PCL as a biomaterial for 3D printing for bone regeneration, and advances made in the field. The specific focus is on the different 3D printing techniques used for this purpose and various modification that can enhance bone regeneration following the development pathways. We further describe the effect of various scaffold characteristics on bone regeneration both in vitro and the translational assessment of these 3D printed PCL scaffolds in animal studies. The generated knowledge will help understand cell-material interactions of 3D printed PCL scaffolds, to further improve scaffold chemistry and design that can replicate bone developmental processes and can be translated clinically.

Increasing Rates of Herpes Zoster Ophthalmicus and the COVID-19 Pandemic.

Purpose: This epidemiologic study evaluates the variance in incidence of Herpes Zoster (HZ) and Herpes Zoster Ophthalmicus (HZO) within a single healthcare system with an aim to analyze their relationship to the COVID-19 pandemic. Methods: All patients attending the Duke University Health System (DUHS) from January 1, 2018, to December 31, 2021, were included. General and COVID-related trends of HZO and HZ were analyzed based on new ICD-9 or ICD-10 diagnosis codes, compared with the total number of patients seen at DUHS during this period, and the number of reported COVID-19 cases in North Carolina obtained using the CDC data tracker. Results: This study included 16,287 cases of HZ of whom 1,294 (7.94%) presented with HZO. The overall incidence of HZO showed an average yearly increase of 5.6%, however HZ incidence decreased by 5.3% per year. When comparing incidence rates of HZO in the 12-months before and after the COVID-19 pandemic onset in the United States (March 2020), the average incidence from March 2020 to February 2021 was 27.6 ± 11.6 compared to 18.0 ± 2.7 from March 2019 to February 2020 (p = 0.01). Moreover, 10/12 (83.3%) of the months had a higher incidence rate of HZO in the post-COVID onset year compared to their corresponding month in the pre-COVID year. Conclusion: The results show HZO incidence may be increasing, despite an overall lower HZ incidence. This could suggest a distinct mechanism for HZO appearance. The COVID pandemic, directly or indirectly, may have accelerated the already increasing HZO incidence.

Effect of Pore Defects on Uniaxial Mechanical Properties of Bulk Hexagonal Hydroxyapatite: A Molecular Dynamics Study.

Hydroxyapatite (HAP) is a calcium apatite bioceramic used in various naturally-derived and synthetic forms for bone repair and regeneration. While useful for the regrowth of osseus tissue, the poor load-bearing capacity of this material relative to other biomaterials is worsened by the propensity for pore formation during the synthetic processing of scaffolds, blocks, and granules. Here we use molecular dynamics (MD) simulations to improve the current understanding of the defect-altered uniaxial mechanical response in hexagonal HAP single crystals relative to defect-free structures. The inclusion of a central spherical pore within a repeated lattice was found to reduce both the failure stress and failure strain in uniaxial tension and compression, with up to a 30% reduction in maximum stress at the point of failure compared to a perfect crystalline structure observed when a 30 Å diameter pore was included. The Z axis ([0 0 0 1] crystalline direction) was found to be the least susceptible to pore defects in tension but the most sensitive to pore inclusion in compression. The deformation mechanisms are discussed to explain the observed mechanical responses, for which charge imbalances and geometric stress concentration factor effects caused by pore inclusion play a significant role.

Polymer-derived SiOC reinforced with core-shell nanophase structure of ZrB2/ZrO2 for excellent and stable high-temperature microwave absorption (up to 900 °C).

Microwave absorbing materials for high-temperature harsh environments are highly desirable for aerodynamically heated parts and engine combustion induced hot spots of aircrafts. This study reports ceramic composites with excellent and stable high-temperature microwave absorption in air, which are made of polymer-derived SiOC reinforced with core-shell nanophase structure of ZrB2/ZrO2. The fabricated ceramic composites have a crystallized t-ZrO2 interface between ZrB2 and SiOC domains. The ceramic composites exhibit stable dielectric properties, which are relatively insensitive to temperature change from room temperature to 900 °C. The return loss exceeds - 10 dB, especially between 28 and 40 GHz, at the elevated temperatures. The stable high-temperature electromagnetic (EM) absorption properties are attributed to the stable dielectric and electrical properties induced by the core-shell nanophase structure of ZrB2/ZrO2. Crystallized t-ZrO2 serve as nanoscale dielectric interfaces between ZrB2 and SiOC, which are favorable for EM wave introduction for enhancing polarization loss and absorption. Existence of t-ZrO2 interface also changes the temperature-dependent DC conductivity of ZrB2/SiOC ceramic composites when compared to that of ZrB2 and SiOC alone. Experimental results from thermomechanical, jet flow, thermal shock, and water vapor tests demonstrate that the developed ceramic composites have high stability in harsh environments, and can be used as high-temperature wide-band microwave absorbing structural materials.

Prolonged in situ self-healing in structural composites via thermo-reversible entanglement.

Natural processes continuously degrade a material's performance throughout its life cycle. An emerging class of synthetic self-healing polymers and composites possess property-retaining functions with the promise of longer lifetimes. But sustained in-service repair of structural fiber-reinforced composites remains unfulfilled due to material heterogeneity and thermodynamic barriers in commonly cross-linked polymer-matrix constituents. Overcoming these inherent challenges for mechanical self-recovery is vital to extend in-service operation and attain widespread adoption of such bioinspired structural materials. Here we transcend existing obstacles and report a fiber-composite capable of minute-scale and prolonged in situ healing - 100 cycles: an order of magnitude higher than prior studies. By 3D printing a mendable thermoplastic onto woven glass/carbon fiber reinforcement and co-laminating with electrically resistive heater interlayers, we achieve in situ thermal remending of internal delamination via dynamic bond re-association. Full fracture recovery occurs below the glass-transition temperature of the thermoset epoxy-matrix composite, thus preserving stiffness during and after repair. A discovery of chemically driven improvement in thermal remending of glass- over carbon-fiber composites is also revealed. The marked lifetime extension offered by this self-healing strategy mitigates costly maintenance, facilitates repair of difficult-to-access structures (e.g., wind-turbine blades), and reduces part replacement, thereby benefiting economy and environment.

Diverse tsunamigenesis triggered by the Hunga Tonga-Hunga Ha'apai eruption.

On the evening of 15 January 2022, the Hunga Tonga-Hunga Ha'apai volcano1 unleashed a violent underwater eruption, blanketing the surrounding land masses in ash and debris2,3. The eruption generated tsunamis observed around the world. An event of this type last occurred in 1883 during the eruption of Krakatau4, and thus we have the first observations of a tsunami from a large emergent volcanic eruption captured with modern instrumentation. Here we show that the explosive eruption generated waves through multiple mechanisms, including: (1) air-sea coupling with the initial and powerful shock wave radiating out from the explosion in the immediate vicinity of the eruption; (2) collapse of the water cavity created by the underwater explosion; and (3) air-sea coupling with the air-pressure pulse that circled the Earth several times, leading to a global tsunami. In the near field, tsunami impacts are strongly controlled by the water-cavity source whereas the far-field tsunami, which was unusually persistent, can be largely described by the air-pressure pulse mechanism. Catastrophic damage in some harbours in the far field was averted by just tens of centimetres, implying that a modest sea level rise combined with a future, similar event would lead to a step-function increase in impacts on infrastructure. Piecing together the complexity of this event has broad implications for coastal hazards in similar geophysical settings, suggesting a currently neglected source of global tsunamis.

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head.

Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose significant activity limitations and the need for multiple revision surgeries with increasing risk of complication. Early detection of AVN requires a high level of suspicion as diagnostic techniques such as X-rays are not sensitive in the early stages of the disease. There are multiple etiologies that can lead to this disease. In the pediatric and adolescent population, trauma is a commonly recognized cause of AVN. The understanding of the pathophysiology of the disease is limited, adding to the challenge of devising a clinically effective treatment strategy. Surgical techniques to prevent progression of the disease and avoid total hip replacement include core decompression, vascular grafts, and use of bone-marrow derived stem cells with or without adjuncts, such as bisphosphonates and bone morphogenetic protein (BMP), all of which are partially effective only in the very early stages of the disease. Further, these strategies often only improve pain and range of motion in the short-term in some patients and do not predictably prevent progression of the disease. Tissue engineering strategies with the combined use of biomaterials, stem cells and growth factors offer a potential strategy to avoid metallic implants and surgery. Structural, bioactive biomaterial platforms could help in stabilizing the femoral head while inducing osteogenic differentiation to regenerate bone and provide angiogenic cues to concomitantly recover vasculature in the femoral head. Moreover, injectable systems that can be delivered using a minimal invasive procedure and provide mechanical support the collapsing femoral head could potentially alleviate the need for surgical interventions in the future. The present review describes the limitations of existing surgical methods and the recent advances in tissue engineering that are leading in the direction of a clinically effective, translational solution for AVN in future.

Study of nanoscale deformation mechanisms in bulk hexagonal hydroxyapatite under uniaxial loading using molecular dynamics.

Hydroxyapatite (HAP) is a natural bioceramic which is currently used in scaffolds and coatings for the regrowth of osseous tissue but offers poor load-bearing capacity compared to other biomaterials. The deformation mechanisms responsible for the mechanical behavior of HAP are not well understood, although the advent of multiscale modeling offers the promise of improvements in many materials through computational materials science. This work utilizes molecular dynamics to study the nanoscale deformation mechanisms of HAP in uniaxial tension and compression. It was found that deformation mechanisms vary with loading direction in tension and compression leading to significant compression/tension asymmetry and crystal anisotropy. Bond orientation and geometry relative to the loading direction was found to be an indicator of whether a specific bond was involved in the deformation of HAP in each loading case. Tensile failure mechanisms were attributed to stretching and failure in loading case-specific ionic bond groups. The compressive failure mechanisms were attributed to coulombic repulsion in each case, although loading case-specific bond group rotation and displacement were found to affect specific failure modes. The elastic modulus was the highest for both tension and compression along the Z direction (i.e. normal to the basal plane), followed by Y and X.

Lumbar Spine Paraspinal Muscle and Intervertebral Disc Height Changes in Astronauts After Long-Duration Spaceflight on the International Space Station.

STUDY DESIGN: Prospective case series. OBJECTIVE: Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station. The long-term objective of this project is to promote spine health and prevent spinal injury during space missions and here on Earth. SUMMARY OF BACKGROUND DATA: National Aeronautics and Space Administration (NASA) crewmembers have a 4.3 times higher risk of herniated IVDs, compared with the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in approximately 5 cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described. METHODS: Six NASA crewmembers were imaged supine with a 3 Tesla magnetic resonance imaging. Imaging was conducted preflight, immediately postflight, and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle, and posterior sections of all lumbar levels. Repeated measures analysis of variance was used to determine significance at P < 0.05, followed by post-hoc testing. RESULTS: Paraspinal lean muscle mass, as indicated by the FCSA, decreased from 86% of the total PSM cross-sectional area down to 72%, immediately after the mission. Recovery of 68% of the postflight loss occurred during the next 6 weeks, still leaving a significantly lower lean muscle fractional content compared with preflight values. In contrast, lumbar IVD heights were not appreciably different at any time point. CONCLUSION: The data reveal lumbar spine PSM atrophy after long-duration spaceflight. Some FCSA recovery was seen with 46 days postflight in a terrestrial environment, but it remained incomplete compared with preflight levels. LEVEL OF EVIDENCE: 4.

Caste-specific tyramides from Myrmicine ants.

Analysis of the extracts of male ants of Monomorium minimum and Monomorium ebeninum by GC-MS and GC-FTIR revealed the presence of tyramides 2 and 4c, for which the structures were established by comparison with synthetic samples. These compounds and their analogues 1 and 3 were also found in males of other Monomorium species, males of Myrmicaria opaciventris, and males of several Solenopsis (Diplorhoptrum) species. Vapor-phase FTIR spectra revealed critically important structural clues to two of the tyramides, which had methyl branching in the tyramide acyl moiety. Tyramide 4c exhibited a strong intramolecular amide NH hydrogen bond where an alpha-keto group was deduced to be present in the acyl moiety and also showed the overlap of this ketone group frequency with that of the amide nu(C horizontal lineO). The biological function of these compounds is uncertain; however, their role in ant-mating behavior may be suggested by a large body of evidence.

HIV-1 Vpr activates the DNA damage response in renal tubule epithelial cells.

HIV-associated nephropathy (HIVAN) is a major cause of HIV-related morbidity and mortality. Pathogenesis involves direct infection of the glomerular and tubular epithelial cells leading to characteristic disorder. Recently, we have shown that HIV-1 Vpr causes hypertrophy, hyperploidy, and apoptosis. Here, we report that Vpr activates the DNA damage response resulting in the observed renal phenotype. Renal sections from the HIVAN transgenic mouse model and human biopsies both show an abundant DNA damage response.