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Implant-associated infections remain a challenge in biomedical engineering and prevention of such complications is a topical subject. For that, local drug delivery is associated with a number of advantages over systemic antibiosis. In this context, incorporation of antibiotic drugs into fibrous nonwovens is a promising approach for the generation of antiinfective implant envelopes or wrappings. Such materials can be manufactured in large scale and electrospinning process is suitable for a wide range of drugs to be incorporated. With regard to increasing numbers of pacemaker implantations and associated risk factors for infections, biodegradable ceftriaxone loaded poly(L-lactide)-co-poly(ethylene glycol) (PLLA-co-PEG) nonwovens have been characterised concerning the influence of the drug on morphology, thermal and mechanical properties and drug release behaviour. Our results show that the chosen material combination is promising for further approaches towards an antiinfective nonwoven pacemaker envelope.

Various manufacturing techniques are available for polymer stent fabrication. Polymer semi-finished products can be prepared using solvent based methods, e.g. dip coating, as well as thermal processes, e.g. extrusion. These different methods may lead to an altered polymer crystal structure, resulting in a different deformation mechanism during mechanical stress. For the material property characterization needed for implant development, the test specimens usually are prepared using laser-cut or die-cut methods. Due to these different preparation protocols, a change in polymer microstructure, causing a material property variation, may also result. For this purpose, comparison of laser-cut versus die-cut of PLLA films has been performed. PLLA films have been prepared by dip-coating and were evaluated with respect to structural, thermal, and mechanical properties. In this study, a combination of uniaxial tensile tests, SEM and DSC studies was used. The results of the mechanical tests showed drastic differences in the elongations at break of die-cut specimens compared to laser-cut ones. The results point out formation of complex crystal structures during the manufacturing process. By the use of SEM imaging and DSC measurements, we were able to attribute these changes to the different plastic deformation mechanisms.

The regeneration of the osteochondral unit represents a challenge due to the distinct cartilage and bone phases. Current strategies focus on the development of multiphasic scaffolds that recapitulate features of this complex unit and promote the differentiation of implanted bone-marrow derived stem cells (BMSCs). In doing so, challenges remain from the loss of stemness during in vitro expansion of the cells and the low control over stem cell activity at the interface with scaffolds in vitro and in vivo. Here, this work scaffolds inspired by the bone marrow niche that can recapitulate the natural healing process after injury. The construct comprises an internal depot of quiescent BMSCs, mimicking the bone marrow cavity, and an electrospun (ESP) capsule that "activates" the cells to migrate into an outer "differentiation-inducing" 3D printed unit functionalized with TGF-β and BMP-2 peptides. In vitro, niche-inspired scaffolds retained a depot of nonproliferative cells capable of migrating and proliferating through the ESP capsule. Invasion of the 3D printed cavity results in location-specific cell differentiation, mineralization, secretion of alkaline phosphatase (ALP) and glycosaminoglycans (GAGs), and genetic upregulation of collagen II and collagen I. In vivo, niche-inspired scaffolds are biocompatible, promoted tissue formation in rat subcutaneous models, and regeneration of the osteochondral unit in rabbit models., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Minimally invasive surgery procedures are of utmost relevance in clinical practice. However, the associated mechanical stress on the material poses a challenge for new implant developments. In particular PLLA, one of the most widely used polymeric biomaterials, is limited in its application due to its high brittleness and low elasticity. In this context, blending is a conventional method of improving the performance of polymer materials. However, in implant applications and development, material selection is usually limited to the use of medical grade polymers. The focus of this work was to investigate the extent to which blending poly-l-lactide (PLLA) with low contents of a selection of five commercially available medical grade polyurethanes leads to enhanced material properties. The materials obtained by melt blending were characterized in terms of their morphology and thermal properties, and the mechanical performance of the blends was evaluated taking into account physiological conditions. From these data, we found that mixing PLLA with Pellethane 80A is a promising approach to improve the material's performance, particularly for stent applications. It was found that PLLA/Pellethane blend with 10% polyurethane exhibits considerable plastic deformation before fracture, while pure PLLA fractures with almost no deformation. Furthermore, the addition of Pellethane only leads to a moderate reduction in elongation at yield and yield stress. In addition, dynamic mechanical analysis for three different PLLA/Pellethane ratios was performed to investigate thermally induced shape retention and shape recovery of the blends., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

In the biomedical field, nanofiber materials are gaining increasing application. For material characterization of nanofiber fabrics, tensile testing and scanning electron microscopy (SEM) are established standards. However, tensile tests provide information about the entire sample without information about single fibers. Conversely, SEM images examine individual fibers, but cover only a small section near the surface of the sample. To gain information on failure at the fiber level under tensile stress, recording of acoustic emission (AE) is a promising method, but challenging due to weak signal intensity. Using AE recording, beneficial findings can be obtained even on "invisible" material failure without affecting tensile tests. In this work, a technology for recording weak ultrasonic AE of tearing nanofiber nonwovens is presented, which uses a highly sensitive sensor. Functional proof of the method using biodegradable PLLA nonwoven fabrics is provided. The potential benefit is demonstrated by unmasking significant AE intensity in an almost imperceptible bend in the stress-strain curve of a nonwoven fabric. AE recording has not yet been performed on standard tensile tests of unembedded nanofiber material intended for safety-related medical applications. The technology has the potential to enrich the spectrum of testing methods, even those not confined to medical field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Novel 3D printing techniques enable the development of medical devices with drug delivery systems that are tailored to the patient in terms of scaffold shape and the desired pharmaceutically active substance release. Gentle curing methods such as photopolymerization are also relevant for the incorporation of potent and sensitive drugs including proteins. However, retaining the pharmaceutical functions of proteins remains challenging due to the possible crosslinking between the functional groups of proteins, and the used photopolymers such as acrylates. In this work, the in vitro release of the model protein drug, albumin-fluorescein isothiocyanate conjugate (BSA-FITC) from differently composed, photopolymerized poly(ethylene) glycol diacrylate (PEGDA), an often employed, nontoxic, easily curable resin, was investigated. Different PEGDA concentrations in water (20, 30, and 40 wt %) and their different molecular masses (4000, 10,000, and 20,000 g/mol) were used to prepare a protein carrier with photopolymerization and molding. The viscosity measurements of photomonomer solutions revealed exponentially increasing values with increasing PEGDA concentration and molecular mass. Polymerized samples showed increasing medium uptake with an increasing molecular mass and decreasing uptake with increasing PEGDA content. Therefore, the modification of the inner network resulted in the most swollen samples (20 wt %) also releasing the highest amount of incorporated BSA-FITC for all PEGDA molecular masses.

Background: Evidence regarding clinically relevant effects of interventions aiming at reducing polypharmacy is weak, especially for the primary care setting. This study was initiated with the objective to achieve clinical benefits for older patients (aged 75+) by means of evidence-based reduction of polypharmacy (defined as ≥8 prescribed drugs) and inappropriate prescribing in general practice., Methods: The cluster-randomised controlled trial involved general practitioners and patients in a northern-Italian region. The intervention consisted of a review of patient's medication regimens by three experts who gave specific recommendations for drug discontinuation. Main outcome measures were non-elective hospital admissions or death within 24 months (composite primary endpoint). Secondary outcomes were drug numbers, hospital admissions, mortality, falls, fractures, quality of life, affective status, cognitive function., Results: Twenty-two GPs/307 patients participated in the intervention group, 21 GPs/272 patients in the control group. One hundred twenty-five patients (40.7%) experienced the primary outcome in the intervention group, 87 patients (32.0%) in the control group. The adjusted rates of occurrence of the primary outcome did not differ significantly between the study groups (intention-to-treat analysis: adjusted odds ratio 1.46, 95%CI 0.99-2.18, p = 0.06; per-protocol analysis: adjusted OR 1.33, 95%CI 0.87-2.04, p = 0.2). Hospitalisations as single endpoint occurred more frequently in the intervention group according to the unadjusted analysis (OR 1.61, 95%CI 1.03-2.51, p = 0.04) but not in the adjusted analysis (OR 1.39, 95%CI 0.95-2.03, p = 0.09). Falls occurred less frequently in the intervention group (adjusted OR 0.55, 95%CI 0.31-0.98; p = 0.04). No significant differences were found regarding the other outcomes. Definitive discontinuation was obtained for 67 (16.0%) of 419 drugs rated as inappropriate. About 6% of the prescribed drugs were PIMs., Conclusions: No conclusive effects were found regarding mortality and non-elective hospitalisations as composite respectively single endpoints. Falls were significantly reduced in the intervention group, although definitive discontinuation was achieved for only one out of six inappropriate drugs. These results indicate that (1) even a modest reduction of inappropriate medications may entail positive clinical effects, and that (2) focusing on evidence-based new drug prescriptions and prevention of polypharmacy may be more effective than deprescribing., Trial Registration: Current Controlled Trials (ID ISRCTN: 38449870), date: 11/09/2013., (© 2021. The Author(s).)

Large skull bone defects of the cranial vault can result from various reasons. Reconstruction of these defects is performed for protective and aesthetic reasons but is also required for adequate intracranial homeostasis. Computer-aided-design/computer-aided-manufacturing (CAD/CAM) patient-specific skull implants have become the most valuable alternative to the traditional methods of reconstruction and a growing number of publications is dealing with this topic in adults. Literature related to the application of these implants in pediatric cranioplasty is, however, still scarce.The authors present a case of a 9-year-old boy, where cranioplasty using a CAD/CAM additive manufactured titanium implant led to improvement of symptoms attributed to cerebrospinal fluid circulation problems and intracranial homeostasis disbalance. The authors further reflect on what the role of cranioplasty should be in the therapeutic treatment plan.

Both transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) have been proven to effectively correct von Willebrand Factor (vWF) pathologies, however there is limited data simultaneously comparing outcomes of both approaches. We prospectively enrolled patients with severe aortic stenosis referred for TAVI (n = 52) or SAVR (n = 48). In each case, vWF antigen (vWF:Ag), vWF activity (vWF:Ac) and activity-to-antigen (vWF:Ac/Ag) ratio were assessed at baseline, 24 h and 72 h after procedure. VWF abnormalities were defined as reduced vWF:Ac/Ag ratio (< 0.8). Bleeding events in both arms were classified according to Valve Academic Research Consortium (VARC-2) definitions. Overall, there was no difference between patients referred for TAVI and SAVR in vWF:Ac (1.62 ± 0.52 vs 1.71 ± 0.64; p = 0.593), vWF:Ag (1.99 ± 0.81 vs 2.04 ± 0.81; p = 0.942) or vWF:Ac/Ag ratio (0.84 ± 0.16 vs 0.85 ± 0.12; p = 0.950). Pathological vWF:Ac/Ag ratio was found in 20 (38%) TAVI and 15 (31%) SAVR patients (p = 0.407). Normalization of vWF:Ac/Ag ratio at day 3 after procedure was achieved in 19 (95%) TAVI and 13 (87%) SAVR patients (p = 0.439). Similar prevalence of major or life-threatening bleedings (MLTB) after TAVI and SAVR in entire groups was observed (19% vs. 23%, p = 0.652). VWF abnormalities were associated with higher incidence of MLTB in SAVR (53% vs 9%, p < 0.001), but not TAVI (15% vs. 22%, p = 0.132). Accordingly, in receiver-operating characteristic curve analysis vWF:Ac/Ag ratio < 0.8 showed significant sensitivity and specificity for predicting MLTB in SAVR group (AUC 0.735, 95% CI 0.538-0.931, p = 0.019). We proved that abnormal function of vWF is corrected successfully after both TAVI and SAVR, but vWF abnormalities are predictive of MLTB only in surgical patients.

Objective: Cranioplasty is indicated to restore form and function of bone defects of the neurocranium. Autografts are the gold standard, alloplastic materials are used when autologous bone is unavailable or unsuitable, and increasing evidence supports the use of patient-specific implants (PSIs) for reconstruction. We reviewed our own patient data to assess pre- and intraoperative aspects, complications and costs in patients that were treated with PSIs from titanium or polyetheretherketone (PEEK) for skull bone reconstruction., Methods: We retrospectively evaluated all patients receiving a PSI as at least a secondary reconstruction between 2004 and 2016 at Maastricht University Medical Center. These cases were analyzed for demographics, perioperative surgical and medical aspects, as well as costs., Results: In total 30 patients received PSIs, of which 20 were included in this study. Duration of PSI placement was not statistically different between group I, where previously placed reconstruction material was still in situ, and group II, where no remaining previously placed reconstruction material was present (group I: 104 ± 27 mins, group II: 86 ± 36 mins; p = 0.27). Postoperatively, 2 patients experienced complications (10%). Costs of obtaining the PSIs were not significantly different between group I and group II (group I: mean EUR 7536 ± 2759, group II: mean EUR 8351 ± 2087, p = 0.51)., Conclusion: Treatment of skull bone defects in repeated reconstruction requires an optimal preoperative planning and intraoperative procedure. In this retrospective study comparing repeatedly reconstructed cases with and without remaining previously placed reconstruction material present at the surgical site, we could not find significant differences in the duration of the surgical procedure nor costs of obtaining the PSIs. The protocol followed at MUMC for preoperative planning, manufacturing, and surgery, represents the current state-of-the-art treatment., (Copyright © 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Patient specific implants have been used for the reconstruction of large skull bone defects. Several therapeutic effects have been suggested in current literature but were never objectified. The aim of the current study was to evaluate the change in quality of life, pain, aesthetics, and the surgical and medical outcomes after reconstruction of large skull bone defects with titanium or polyetheretherketone (PEEK) implants., Methods: We retrospectively evaluated 29 consecutive patients receiving a patient specific skull implant between November 2004 and December 2015. Twenty-one patients received PEEK implants and eight received titanium implants. Data was acquired regarding quality of life, aesthetics, pain, demographics and complications. Quality of life was measured using the Glasgow Benefit Inventory (GBI). Additional questions were asked concerning pain, satisfaction and aesthetics., Results: The mean total GBI-score was +26.1 (95%CI 16.8-35.4, p < 0.001). Headache complaints or pain in the operation site improved in 75.0% and 77.8% of these patients, respectively. In 8.0% an increase was seen with regard to both variables., Conclusion: Reconstruction of skull bone defects with PEEK and titanium patient specific implants gave a statistically significant improvement in quality of life. Furthermore, it decreased pain and headaches and gave aesthetically good results., (Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Different options exist for the reconstruction of craniectomy defects following interval cranioplasty. The standard procedure is still based on the re-implantation of autogenous bone specimen which can be stored in the abdominal wall or be cryopreserved. Alternatively patient-specific implants (PSIs) can be used. We conducted a retrospective study based on 50 consecutive patients with skull bone defects of 100 cm(2) or more being operated on by the same team of surgeons. Thirty-three patients agreed to take part in the study. Seventeen patients who underwent reconstruction with PSIs (titanium and polyether ether ketone, PEEK) (follow-up, 43 months [range, 3-93]) were compared with 16 control subjects who had autogenous bone grafts re-implanted (follow-up, 32 months [range, 5-92]). Criteria analyzed were the success and complication rates, operation time, duration of hospitalization and the treatment costs. Complication rate and the rate of reoperation were significantly lower, and the hospital stay was shorter in the PSI group. The treatment costs for reconstruction with autogenous bone were considerably lower than skull bone reconstruction based on PSIs (average costs: 10849.91 €/patient versus 15532.08 €/patient with PSI). Due to biological reasons some of the autogenous bone implants fail due to infection and resorption and the patients have to undergo another operation with implantation of a PSI in a secondary attempt. For those patients the highest overall treatment costs must be calculated (average costs: 26086.06 €/patient with secondary stage PSI versus 15532.08 €/patient with primary stage PSI)., Conclusion: High success rates and reliability of PSIs may change the treatment strategy in patients undergoing interval cranioplasty., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic diseases affect more than half of the population ≥75 years of age in developed countries. Prescription medication use increases with age. Depending on definition, 25-80% of elderly are exposed to polypharmacy. Polypharmacy increases the risk of hospitalization, interactions and adverse drug reactions., Objective: To examine the frequency of medication errors in patients with polypharmacy treated in general practice., Methods: The medications of 169 patients with polypharmacy treated in 22 GP surgeries in Austria were analysed. The analysis identified (i) medication errors, including non-evidence-based medications, dosing errors and potentially dangerous interactions in all patients and (ii) potentially inappropriate medications (PIMs) in the subgroup of elderly patients (≥65 years)., Results: The patients took on average 9.1±3.0 medications per day. The maximum, in one patient, was 20 medications per day. Some 93.5% had at least one non-evidence-based medication. On average, 2.7±1.66 medications per patient were found to be not indicated. At least one dosing error was found in 56.2% of all patients. One potential interaction of the most severe degree (category X interaction) was detected in 1.8% (n = 3) and two such interactions in 0.6% (n = 1). These combinations should have been avoided. Of the 169 patients, 158 were elderly (≥65 years). Of these seniors, 37.3% (n = 59) had at least one PIM according to the PRISCUS list for the elderly., Conclusion: The frequency of medication errors is high in patients with polypharmacy in primary care. Development of strategies (e.g. external medication review) is required to counteract medication errors.

Large skull bone defects resulting from craniotomies due to cerebral insults, trauma or tumours create functional and aesthetic disturbances to the patient. The reconstruction of large osseous defects is still challenging. A treatment algorithm is presented based on the close interaction of radiologists, computer engineers and cranio-maxillofacial surgeons. From 2004 until today twelve consecutive patients have been operated on successfully according to this treatment plan. Titanium and polyetheretherketone (PEEK) were used to manufacture the implants. The treatment algorithm is proved to be reliable. No corrections had to be performed either to the skull bone or to the implant. Short operations and hospitalization periods are essential prerequisites for treatment success and justify the high expenses., (Copyright © 2010 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

7S RNA sequences from the hagfish (Myxiniformes) and lamprey (Petromyzontiformes) were cloned and analyzed. In both species, 7S L RNA (also designated SRP RNA, since it represents the RNA constituent of the signal recognition particle) was clearly detectable. The sequence similarity between the two species was 86%, compared with about 75% similarity between either of these species and mammals. 7S K RNA was also cloned from the lamprey. The similarity between the 7S K RNA of the lamprey and that of mammals was 68%. Interestingly, several interspersed elements were found with nearly 100% similarity compared with mammals. In contrast to the lamprey, no 7S K RNA-related sequences were detectable among hagfish RNA, neither in northern blots nor with the PCR assay. In view of the significant conservation between the 7S K RNA of lamprey and that of mammals (human), this unexpected result clearly separates lamprey and hagfish. In addition, the lack of detectable 7S K RNA sequences in an outgroup, such as amphioxus, indicates that these results do not reflect an autapomorphy of hagfish. Therefore, our data provide additional support to the notion of a sister group relationship between Petromyzontiformes and gnathostomous vertebrates to the exclusion of Myxiniformes.

The diagnosis, pathogenesis and etiology of myocarditis are often difficult to establish with certainty. Consequently, we investigated cellular regulator and effector mechanisms in patients with viral heart disease (Coxsackie B3, influenza, EBV, mumps) as well as other inflammatory heart diseases which could not be classified etiologically. In acute myocarditis there was an elevation of B- and activated T-lymphocytes (OKIa 1-positive) but, in contrast, no significant changes in the activity of peripheral suppressor T-cells (OKT 8-positive). The activity of cell-specific lymphocytic effector mechanisms against vital cardiocytes was unchanged or slightly elevated in myocarditis, while the activity of the less target cell specific natural killer cells, which were measured in vitro against K562 tumor cells, was diminished. These findings are indicative of increased activity of target specific cytotoxic effector mechanisms and a reduction in the activity of nonspecific cellular effector mechanisms in peripheral blood.