Triggered metabolism of adenosine triphosphate as an explanation for the chemical heterogeneity of heterotopic ossification.

Heterotopic ossification (HO), the pathological formation of bone in soft tissues, is a debilitating condition, as well as one of the few instances of de novo bone formation in adults. Chemical mapping of HO tissue showed distinct islands of calcium phosphate within phosphate-deficient, calcium-rich regions, suggesting a transition to apatitic bone mineral from a non-phosphatic precursor. The transition of amorphous calcium carbonate (ACC), a generally suggested bone-mineral precursor, in physiological conditions was thus investigated.

Bioengineering extracellular vesicles: smart nanomaterials for bone regeneration.

In the past decade, extracellular vesicles (EVs) have emerged as key regulators of bone development, homeostasis and repair. EV-based therapies have the potential to circumnavigate key issues hindering the translation of cell-based therapies including functional tissue engraftment, uncontrolled differentiation and immunogenicity issues. Due to EVs' innate biocompatibility, low immunogenicity, and high physiochemical stability, these naturally-derived nanoparticles have garnered growing interest as potential acellular nanoscale therapeutics for a variety of diseases.

Space habitats for bioengineering and surgical repair: addressing the requirement for reconstructive and research tissues during deep-space missions.

Numerous technical scenarios have been developed to facilitate a human return to the Moon, and as a testbed for a subsequent mission to Mars. Crews appointed with constructing and establishing planetary bases will require a superior level of physical ability to cope with the operational demands. However, the challenging environments of nearby planets (e.

Spectroscopic detection of traumatic brain injury severity and biochemistry from the retina.

Traumatic brain injury (TBI) is a major burden on healthcare services worldwide, where scientific and clinical innovation is needed to provide better understanding of biochemical damage to improve both pre-hospital assessment and intensive care monitoring. Here, we present an unconventional concept of using Raman spectroscopy to measure the biochemical response to the retina in an murine model of TBI. Through comparison to spectra from the brain and retina following injury, we elicit subtle spectral changes through the use of multivariate analysis, linked to a decrease in cardiolipin and indicating metabolic disruption.

Local injection of a hexametaphosphate formulation reduces heterotopic ossification .

Heterotopic ossification (HO), the pathological formation of ectopic bone, is a debilitating condition which can cause chronic pain, limit joint movement, and prevent prosthetic limb fitting. The prevalence of this condition has risen in the military population, due to increased survivorship following blast injuries. Current prophylaxes, which aim to target the complex upstream biological pathways, are inconsistently effective ​and have a range of side-effects that make them unsuitable for combat-injured personnel.

The Quantification of Injectability by Mechanical Testing.

Injectable biomaterials are becoming increasingly popular for the minimally invasive delivery of drugs and cells. These materials are typically more viscous than traditional aqueous injections and may be semi-solid, therefore, their injectability cannot be assumed. This protocol describes a method to objectively assess the injectability of these materials using a standard mechanical tester.

Filling the Gap: A Correlation between Objective and Subjective Measures of Injectability.

Various injectable biomaterials are developed for the minimally invasive delivery of therapeutics. Typically, a mechanical tester is used to ascertain the force required to inject these biomaterials through a given syringe-needle system. However, currently there is no method to correlate the force measured in the laboratory to the perceived effort required to perform that injection by the end user.

Development of the Self Optimising Kohonen Index Network (SKiNET) for Raman Spectroscopy Based Detection of Anatomical Eye Tissue.

Raman spectroscopy shows promise as a tool for timely diagnostics via in-vivo spectroscopy of the eye, for a number of ophthalmic diseases. By measuring the inelastic scattering of light, Raman spectroscopy is able to reveal detailed chemical characteristics, but is an inherently weak effect resulting in noisy complex signal, which is often difficult to analyse. Here, we embraced that noise to develop the self-optimising Kohonen index network (SKiNET), and provide a generic framework for multivariate analysis that simultaneously provides dimensionality reduction, feature extraction and multi-class classification as part of a seamless interface.

Physical Structuring of Injectable Polymeric Systems to Controllably Deliver Nanosized Extracellular Vesicles.

Extracellular vesicles (EVs) are emerging as a promising alternative approach to cell-therapies. However, to realize the potential of these nanoparticles as new regenerative tools, healthcare materials that address the current limitations of systemic administration need to be developed. Here, two technologies for controlling the structure of alginate based microgel suspensions are used to develop sustained local release of EVs, in vitro.

The role of subchondral bone, and its histomorphology, on the dynamic viscoelasticity of cartilage, bone and osteochondral cores.

Objective: Viscoelastic properties of articular cartilage have been characterised at physiological frequencies. However, studies investigating the interaction between cartilage and subchondral bone and the influence of underlying bone histomorphometry on the viscoelasticity of cartilage are lacking.

Method: Dynamic Mechanical Analysis (DMA) has been used to quantify the dynamic viscoelasticity of bovine tibial plateau osteochondral cores, over a frequency sweep from 1 to 88 Hz.

The design of additively manufactured lattices to increase the functionality of medical implants.

The rise of antibiotic resistant bacterial species is driving the requirement for medical devices that minimise infection risks. Antimicrobial functionality may be achieved by modifying the implant design to incorporate a reservoir that locally releases a therapeutic. For this approach to be successful it is critical that mechanical functionality of the implant is maintained.

Post-Traumatic Heterotopic Ossification: An Old Problem in Need of New Solutions.

Heterotopic ossification (HO) is the formation of pathological bone in ectopic sites and it can have serious consequences for functional outcomes. For many years, its main clinical relevance was as a rare complication of elective joint arthroplasty or CNS injury and a number of prophylaxes were developed to mitigate against it in these settings. As a consequence of changes in patterns of wounding and survival in conflicts since the turn of the century, post-traumatic HO has become much more common and case severity has increased.

Left Of Bang Interventions in Trauma: ethical implications for military medical prophylaxis.

Advances in medical capability should be accompanied by discussion of their ethical implications. In the military medical context there is a growing interest in developing prophylactic interventions that will mitigate the effects of trauma and improve survival. The ethics of this novel capability are currently unexplored.

Surface Finish has a Critical Influence on Biofilm Formation and Mammalian Cell Attachment to Additively Manufactured Prosthetics.

Additive manufacturing (AM) technologies enable greater geometrical design freedom compared with subtractive processes. This flexibility has been used to manufacture patient-matched implants. Although the advantages of AM are clear, the optimization at each process stage is often understated.

Towards research combat readiness: prepared, prospective and preapproved.

Research drives the advancement of medical knowledge during war, but planning and execution are too slow to enable early data acquisition. Future conflicts are likely to be shorter and more dispersed, requiring innovation to avoid missing out on the crucial early stages. To seize the initiative, we suggest that a collection of preapproved research studies be designed, stored and maintained within the medical command structure so that they are ready for immediate implementation at the onset of future conflicts, even during the most kinetic early phases of deployment.

Incidence and medical management of bisphosphonate-associated atypical femoral fractures in a major trauma centre: a retrospective observational study.

Background: Atypical femoral fractures (AFFs) are rare events associated with increased duration of bisphosphonate exposure. Recommended management of AFFs include cessation of bisphosphonates and imaging of the contralateral femur. The aims of this study were to identify the local incidence of AFFs in bisphosphonate users and to audit the medical management of AFFs against published recommendations.

Enzymatically regulated demineralisation of pathological bone using sodium hexametaphosphate.

The pathological formation of bone in soft tissue can result in significant disability, prevent prosthetic limbs from fitting, and limit joint movement. A range of conditions exist, which are characterised by this local tissue ossification. The awareness of one such condition, heterotopic ossification, has increased recently due to the extraordinarily high incidence of the condition in military amputees (64.

Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir.

Bedside, Benchtop, and Bioengineering: Physicochemical Imaging Techniques in Biomineralization.

The need to quantify physicochemical properties of mineralization spans many fields. Clinicians, mineralization researchers, and bone tissue bioengineers need to be able to measure the distribution, quantity, and the mechanical and chemical properties of mineralization within a wide variety of substrates from injured muscle to electrospun polymer scaffolds and everything in between. The techniques available to measure these properties are highly diverse in terms of their complexity and utility.

Identifying the Cellular Mechanisms Leading to Heterotopic Ossification.

Heterotopic ossification (HO) is a debilitating condition defined by the de novo development of bone within non-osseous soft tissues, and can be either hereditary or acquired. The hereditary condition, fibrodysplasia ossificans progressiva is rare but life threatening. Acquired HO is more common and results from a severe trauma that produces an environment conducive for the formation of ectopic endochondral bone.

Disassociation at the head-trunnion interface: an unseen complication of modular hip hemiarthroplasty.

A woman in her mid-90s underwent a left uncemented bipolar hemiarthroplasty for an intracapsular femoral neck fracture. Postoperative radiographs at 48h showed a disassociation of the left femoral prosthesis at the head-trunnion interface, with the bipolar head remaining in the acetabulum. There was no preceding trauma and the patient had mobilised postoperatively.