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Background To clinically evaluate 3D print-formed implant process, using cranioplasty as a proof of concept, to examine its effectiveness and utility as a method of intraoperative implant fabrication. Methods Twelve patients had a 3D print-formed template created for patient-specific implant manufacture. Of these patients, 10 received intraoperatively formed polymethylmethacrylate cranioplasty implants between 2013 and 2019. The 3D print-formed implant templates produced to manufacture these patient-specific implants were generated using patient computed tomography scans and 3D printed using fused deposition modelling technology. Cosmetic and functional results were determined by participating surgeons, in conjunction with a patient questionnaire. Results The functional results and stability of the implants were deemed to be favourable by participating surgeons. Three of the 10 patients completed a post-cranioplasty survey, all of whom judged their cosmetic results as good or excellent. At time of writing, the rate of surgical revision was zero and without clinically adverse outcomes. Conclusions 3D print-formed implants are an effective method of patient-specific implant formation.

Kidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury.A novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation.In both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants.Protection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.

A variety of assessment tools are currently available to help clinicians assess Sports Related Concussion (SRC). Currently, the most widely available tools are neither objective nor portable, and are therefore not ideal for assessment at the site and time of a suspected injury. A portable system was developed to deliver a measurement of the steady-state visual-evoked potential (SSVEP). This system involved a smartphone housed in a Google Cardboard frame, which delivered a 15-Hz flicker visual stimulus while an electroencephalography (EEG) headset recorded EEG signals. Sixty-five rugby union players were tested during their regular season and were stratified into healthy, concussed, and recovered groups based on clinical examination. Their SSVEP response was quantified into a signal-to-noise ratio (SNR). The SNRs of players in each study group were summarized. Additionally, the SNRs of individual players who had baseline, post-injury, and post-recovery readings were analyzed. Sixty-five participants completed a baseline evaluation to measure their SSVEP. Twelve of these participants sustained a medically diagnosed concussion and completed SSVEP re-testing within 72 h. Eight concussed players received follow-up SSVEP testing after recovery. Concussed participants had a lower SNR [2.20 (2.04–2.38)] when compared to their baseline [4.54 (3.79–5.10)]. When clinically recovered, participant SNR was not significantly different to their baseline [4.82 (4.13–5.18)]. The baseline SNRs of the players who experienced a concussion during the season were not different to those of players who did not experience a concussion [4.80 (4.07–5.68)]. This is the first study to identify differences in SSVEP responses in male amateur rugby union players with and without concussion. It is also the first SSVEP demonstration for concussion evaluation at point-of-care. SSVEPs are significantly attenuated in the presence of concussion in these male athletes. Individuals returned to their baseline SSVEP following clinical recovery from the concussive injury. The use of SSVEPs has the potential to be a supplemental aid for the assessment and management of concussion.

The clinical use of photodynamic therapy (PDT) with rose bengal (RB) is emerging as an effective t reatment for a range of applications given its non-invasive and localised mode of delivery. In particular, rose bengal PDT has shown promising antifungal action in vitro. While focus has largely been on the physical and chemical impacts of PDT on the cell, an understanding of the role of genetics underpinning the cellular response is still limited. We have, therefore, reported a screen of the entire non-essential gene library of the model organism, Saccharomyces cerevisiae, using rose bengal PDT to ascertain the key genetic pathways affecting fungal tolerance to PDT. We also investigated the dosage of PDT required to eradicate Trichophyton rubrum spores, the main causative organism of onychomycosis infection. Following this, we conducted a pilot patient study of six patients (seven toenails) for the treatment of onychomycosis using rose bengal PDT (140 μM RB and ~763 J/cm2 green light), where the clinical treatment protocol was developed on the basis of the in vitro outcomes. The key biochemical pathways identified by the genetic screen as having altered tolerance to PDT included ergosterol biosynthesis, vacuolar acidification, and purine/S-adenosyl-L-methionine biosynthesis. The subsequent pilot patient study saw the complete cure of onychomycosis for all patients within three to five treatment sessions in the absence of pain or other local side effects. The outcome of the genetic screen for tolerance may thus inform the development of efficient clinical treatments using rose bengal PDT.

ObjectiveThis study aims to utilize a portable system capable of measuring steady-state visual evoked potentials (SSVEP) to investigate their use as an objective electrophysiologic biomarker for concussion.BackgroundThe most pressing issues in relation to sports related concussion (SRC) involves accurate and timely diagnosis, for a safe return to play criteria. Despite the vast range of tools available to help clinicians assess concussion, most are subjective, non-portable, and therefore non-ideal for unbiased application at the site and time of a suspected injury.Design/MethodsThis system applied a smartphone housed in a VR-frame delivering a 15-Hz flickering stimulus while a wireless electroencephalography (EEG) headset recorded EEG signals. Sixty-five male amateur rugby athletes (20.9 ± 2.3 years-old) were tested throughout a season and were stratified into healthy, concussed, and recovered groups based on clinical examinations pre- and post-competitive games. Players SSVEP responses was quantified into a signal-to-noise ratio (SNR) and summarized into respective study-groups for comparison of medians with 25th–75th interquartile range.ResultsAll sixty-five participants completed a baseline evaluation preseason. Twelve participants sustained a diagnosed concussion during the season and were retested within 72 h of injury. Eight concussed players received additional SSVEP testing following a 2-week recovery period. Concussed participants had a significantly lower SNR [2.20 (2.04–2.38)] when compared to their baseline [4.54 (3.79–5.10)]. When clinically recovered, participant SNR [4.82 (4.13–5.18)] was not significantly different to their baseline. Baseline SNR of concussed and non-concussed participants [4.80 (4.07–5.68)] did not significantly differ.ConclusionsThis is the first study to show that SSVEPs are significantly attenuated in the presence of concussion in male athletes. Concussed individuals' ability to generate SSVEP appear to recover following clinical recovery. The observations of this study indicate SSVEP have the potential to be a supplemental aid for the assessment and management of concussion at point-of-care.

Analysis of current literature highlights a wide variation in reported infection risk for different materials in cranial repair. The purpose of these composite materials are to mimic natural bone and assist in restoring function (structurally and aesthetically) to the human skull. This review aims to examine the meta-data in order to provide an amalgamated overview of potential trends between implant material, manufacturing method and infection risk, in order to provide a core reference point for future studies surrounding emerging biomedical materials in the fields of cranioplasty by providing base point for understanding the capabilities and limitations of current technologies. Methods: A search for articles was conducted, with the following criteria seen as fundamental in providing an accurate picture of the current landscape: publication in the last decade, provision of a numerical value for both number of implants and infection cases, patient sample of 10+, adult patients, and cranioplasty/cranial repair. Results: A total of 41 articles were seen to meet the author’s inclusion criteria. Average infection rates per material ranged between 2.04% and 10.98%. The results indicate that there is variation between materials in regards to total infection risk, however, depending on the materials compared, this value may be insignificant. Alternative risk factors associated with infection, including surgical time, revisions and previous infection, have a greater impact on infection potential than material variation. Comparison of fabrication methods did highlight a notable effect on average infection rate. Trends can be observed showing that materials with greater levels of surface interaction and active support of tissue ingrowth presented greater infection resistance. Such characteristics are due to the physical structures of the implants. Conclusions: It can be said that the manufacturing methods can influence biomedical materials to assist in minimizing implant infection risk.

Intramedullary (IM) nails are routinely used to stabilize long bone fractures. They can however lead to stress shielding, pain, migration, obstruct hematopoietic tissue, become a loci for infection, and require subsequent surgical retrieval. Novel intra-osseous scaffold (IOS™) prototypes for fracture healing have been developed to function as a regenerative scaffold to enhance callous formation under mechanically stabilized conditions then resorb. Prototype fixation pins and rod systems were formed from glass-reinforced-glass. Flexion, torsion and shear tests were performed to evaluate the composite pins and rods. A modular rod design was successfully deployed and dilated while in a deformable state. When fitted and gripping the intramedullary canal then set in a rigid state. An obliquely sectioned ovine femur was used as a long bone fracture model for deployment and mechanical verification. Flexural support provided by the intramedullary scaffold was superior to multiple k-wire fixation, while the k-wire approach was more stabilizing under torsional loads. Glass reinforced glass samples were mechanically tested after soaking for up to 4 weeks in saline. Strength and modulus of the composite was reduced to approximately 25% of initial values after 2 weeks.

Chronic non-healing wounds are a common complication of diabetes. Prolonged inflammation and decreased matrix accumulation may contribute. Connective tissue growth factor (CTGF) is induced during normal wound healing, but its regulation in diabetic wounds is unknown. We developed a primate model for the study of in vivo wound healing in baboons with long diabetes duration.Drum implants were placed subcutaneously into thighs of diabetic and non-diabetic control baboons. After 2 and 4 weeks the skin incision sites were removed for measurement of breaking strength and epithelial thickness. Drum implants were removed for analysis of granulation tissue and inflammatory cells, CTGF and tissue inhibitor of matrix metalloproteinase (TIMP-1). Degradation of added CTGF by wound fluid was also examined.Healed incision site skin was stiffer (less elastic) in diabetic baboons and epithelial remodelling was slower compared with controls. Granulation tissue from diabetic baboons was reduced at 2 and 4 weeks, with increased vessel lumen areas at 4 weeks. Macrophages were reduced while neutrophils persisted in diabetic tissue. In diabetic wound tissue at 4 weeks there was less CTGF induced, as shown by immunohistochemistry, compared with controls. In contrast, immunoreactive fragments of CTGF were significantly increased in whole tissue lysate in diabetic baboons, suggesting that CTGF is redistributed in diabetes from granulation tissue into wound fluid. When recombinant human CTGF was co-incubated with wound fluid, increased CTGF degradation products were observed in both control and diabetic samples.This baboon model of wound healing reflects the abnormal microenvironment seen in human diabetic wounds and provides insights into the dysregulation of CTGF in diabetic wounds.

Nail fungal infections are notoriously persistent and difficult to treat which can lead to severe health impacts, particularly in the immunocompromized. Current antifungal treatments, including systemic and topical drugs, are prolonged and do not effectively provide a complete cure. Severe side effects are also associated with systemic antifungals, such as hepatotoxicity. Light treatments of onychomycosis are an emerging therapy that has localized photodynamic, photothermal or photoablative action. These treatments have shown to be an effective alternative to traditional antifungal remedies with comparable or better cure rates achieved in shorter times and without systemic side effects. This report reviews significant clinical and experimental studies in the field, highlighting mechanisms of action and major effects related to light therapy; in particular, the impact of light on fungal genetics.

Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken.Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid.Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Woundα-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r=0.406;P<0.001).Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

Hydrogels are currently applied in the treatment of numerous degenerative diseases because of their three dimensional (3D) nature, high water content and wide range of polymers that can be used for their fabrication. Hydrogels have been investigated and commercialized, for example, as soft contact lens-based ophthalmic drug delivery systems. These novel devices improved the bioavailability of ophthalmic drugs and their residence time. Hydrogels are also being investigated to facilitate and augment targeted delivery of chemotherapeutic agents. This approach minimizes significantly the side effects associated with conventional administration of anti-cancer therapeutics. The application of hydrogels as 3D scaffold has recently gained momentum because they can mimic key features of the extracellular matrix. For this reason, hydrogels are representing a viable alternative to traditional tumor xenograft in cancer biology studies. This review highlights recent advances in the development of hydrogels that are applied in degenerative diseases such as ocular, cancer, spine and cartilage degenerative pathologies.

Background Context Discectomy is a common procedure for treating sciatica. However, both the operation and preceding herniated disc alter the biomechanical properties of the spinal segment. The disc mechanics are also altered in patients with chronic contained herniation. The biomechanical properties of the disc can potentially be restored with an elastomeric nucleus replacement implanted via minimally invasive surgery. Purpose The purpose of this study was to determine whether the compressive characteristics of the intervertebral disc after a nucleotomy can be restored with an elastomeric nucleus replacement. Study Design A finite element model of the L4–L5 intervertebral disc was created to investigate the effect of the implantation of an elastomeric nucleus replacement on the biomechanical properties of the disc under axial loading. Method A L4–L5 physiologic intervertebral disc model was constructed and then modified to contain a range by volume of nucleotomies and nucleus replacements. The material properties of the nucleus replacement were based on experimental data for an elastomeric implant. The compressive stiffness, radial annular bulge, and stress distribution of the nucleotomy and nucleus replacement models were investigated under displacement-controlled loading. Results Removal of nucleus pulposus from the physiologic disc reduced the force necessary to compress the disc 2 mm by 50%, altered the von Mises stress distribution, and reduced the outward radial annular bulge. Replacing the natural nucleus pulposus of the physiologic disc with an artificial nucleus reduced the force required to compress the disc 2 mm by 10%, indicating a restoration of disc compressive stiffness. The von Mises stress distribution and annular bulge observed in the disc with an artificial nucleus were similar to that observed in the physiologic disc. Conclusion This study demonstrates that despite having different material properties, a nucleus replacement implant can restore the axial compressive mechanical properties of a disc after a discectomy. The implant carries compressive load and transfers the load into annular hoop stress.