Biology subjects

Baumgartner, C.

Publications and source records attributed to Baumgartner, C..

7 recordsLinked to original sources

bioRxiv2026

Reconstruction of critical-sized mandibular defects in a sheep model using a PLLA-PGA-CC scaffold

IntroductionCritical-sized bone defects cannot heal spontaneously, requiring additional, often burdensome, treatment. Thus, various synthetic substitute materials have been investigated regarding their treatment capacity. Poly-L-lactic acid (PLLA) and polyglycolic acid (PGA) have emerged as promising biodegradable scaffold materials. The addition of inorganic materials such as calcium carbonate (CC) has also been shown to be advantageous. This study investigates the effect on bone regeneration of PLLA-PGA-CC scaffolds in critical-sized bone defects over a two-year observation period using sheep as an animal model. MethodsCritical-sized mandible angle defects were created in twelve female merino sheep. Mandibular defects were reconstructed with PLLA-PGA-CC scaffolds in four sheep, while the remaining eight served as negative control (defects left empty). The scaffolds were manufactured using computer-aided design and manufacturing, incorporating an interconnected porous structure and fixated with polyether ether ketone cages. Bone regeneration was evaluated using computed tomography (CT) imaging at 3, 12, and 24 months postoperatively. Bone volume was assessed quantitatively. Additionally, a histological analysis was performed. ResultsSurgical procedures were successful and without major complications. CT assessment showed more bone regeneration in the scaffold group (mean volume: 7,472 mm3) than in the control group (4,168 mm3, p = 0.1) at 24 months postoperatively. Resorption of the scaffolds and formation of compact lamellar bone tissue were confirmed by histological analysis. However, the osteoconductive properties of the scaffolds were limited, with only minimal ingrowth of bone tissue into the porous structure. In both groups, fibrous tissue infiltration and the formation of cyst-like cavities in the defect region were observed. ConclusionPLLA-PGA-CC scaffolds were found to be biocompatible and enhanced bone regeneration compared to the control group. Due to fibrous tissue infiltration and the lack of osteoconductivity, the suitability of the material for critical-sized bone defect reconstruction is limited.

bioengineering↗

bioRxiv2025

Beyond the Resection: Surgical White Matter Disruption alters Non-Resected Brain Anatomy

Resective neurosurgery is a cornerstone treatment for many neurological conditions. Although traditionally viewed as localised procedure, increasing evidence from advanced magnetic resonance imaging (MRI) shows that also non-resected anatomy can degenerate following surgery. The relationship between local tissue removal and these postoperative changes remains thus far speculative. Here, we investigate the hypothesis that degenerative changes to surgically preserved grey and white matter are mediated by transneuronal degeneration, a deterioration of intact neuronal populations due to lost axonal input. Using a robust structural and diffusion MRI framework, we first identify widespread postoperative atrophy: pronounced cortical thickness decreases near the resection, and extensive white matter impairments across the ipsilateral hemisphere. Importantly, we then link these alterations to surgical white matter disruption, revealing a sequential network atrophy following neurosurgery. Beyond degenerative effects, we also demonstrate often reported structural network reorganisations as an artefact of image processing, indicating limited capacity for macroscale plasticity post-resection. Key PointsO_LIResective neurosurgery can lead to postoperative atrophy of non-resected grey and white matter. Utilising a robust longitudinal neuroimaging framework, we evaluate these changes as consequences of transneuronal degeneration, demonstrating a sequential atrophy of brain anatomy following the loss of surgically disrupted white matter. C_LIO_LIThe majority of severed connections projected to atrophic cortices near the resection, indicating them to be short association fibers. Consecutive white matter atrophy however affected extensive ipsilateral pathways, highlighting a cascading network effect of resective brain surgery. C_LIO_LIWe did not find evidence to support often reported structural reorganisations of large-scale brain networks post-resection. Yet, we demonstrate that evidence typically interpreted as such can be replicated when using non-robust reconstruction methods. C_LI

neuroscience↗

bioRxiv2023

Gene Therapy for Cardiomyopathy associated with Duchenne Muscular Dystrophy in a Pig Model

BackgroundGenetic cardiomyopathies caused by mutations in the dystrophin gene (DMD) are only partially responsive to current pharmacological heart failure treatments, although dilated and arrhythomogenic phenotypes of cardiomyopathy are frequent. ObjectiveIn this study, we tested whether a normalization of Ca2+-handling by forced expression of SERCA2a in cardiomyocytes mitigates heart failure and arrhythmogenesis in a pig model for Duchenne muscular dystrophy (DMD). Methods and resultsMale offspring of pigs lacking DMD exon 52 are characterized by heart failure with reduced ejection fraction (HFrEF, EF 34.5{+/-}1.8% vs. 49.2{+/-}1.0% in control hearts), arrhythmogenesis due to large apical regions of reduced voltage amplitude and sudden cardiac death with a lifespan of usually less than 4 months. Slow antegrade intracoronary infusion of AAV1.SERCA2a (3x1013 virus genomes (vg) per pig) improved left ventricular ejection fraction (EF 47.3{+/-}2.0%, p<0.05) to a similar extent as germline editing of DMD{Delta}52 to DMD{Delta}51-52, inducing a Becker dystrophy (BMD) genotype (EF 46.7{+/-}3.8%). Moreover, AAV.SERCA2a significantly reduced myocardial inflammation and fibrosis and areas of reduced AP amplitude. ConclusionsIn DMD pigs, 3x1013vg/heart of GMP-grade AAV1.SERCA2a sufficed to normalize left ventricular function and improved electrical vulnerability of the heart. Hence, AAV.SERCA2a may serve as a treatment option for DMD cardiomyopathy.

physiology↗

bioRxiv2023

Nociception in chicken embryos, Part III: Analysis of movements before and after application of a noxious stimulus

Many potentially noxious interventions are performed on chicken embryos in research and in the poultry industry. It is therefore in the interest of animal welfare to define the point at which a chicken embryo is capable of nociception. The present part III of a comprehensive study examined the movements of developing chicken embryos with the aim of identifying behavioral responses to aww noxious stimulus. For this purpose, a noxious mechanical stimulus and a control stimulus were applied. The recorded movements of the embryos were evaluated using the markerless pose estimation software DeepLabCut and manual observations. After the application of the noxious stimulus, a significant increase in beak movement was identified in 15- to 18-day-old embryos. In younger embryos, no behavioral changes related to the noxious stimulus were observed. The results indicate that noxious stimuli at the beak base evoke a nocifensive reaction in chicken embryos starting at embryonic day 15.

animal behavior and cognition↗

bioRxiv2023

Nociception in chicken embryos, Part I: Analysis of cardiovascular responses to a mechanical noxious stimulus

While it is assumed that chicken embryos acquire the ability for nociception during the developmental period in the egg, an exact time point has not yet been specified. This study aimed to determine the onset of nociception during embryonic development in chicken. Changes in blood pressure and heart rate (HR) in response to a mechanical noxious stimulus at the base of the beak versus a light touch on the beak in chicken embryos between embryonic days (EDs) 7 and 18 were examined. Mean arterial pressure (MAP) was the most sensitive parameter for assessing cardiovascular responses. Significant changes in MAP in response to a noxious stimulus were detected in embryos at ED16 to ED18, while significant changes in HR were observed on ED17 and ED18. Infiltration anesthesia with the local anesthetic lidocaine significantly reduced reactions in MAP on ED18, so the cardiovascular changes can be assumed to be nociceptive responses.

physiology↗

bioRxiv2023

Nociception in chicken embryos, Part II: Embryonal development of electroencephalic neuronal activity in ovo as a prerequisite for nociception

Chicken culling is forbidden in Germany since 2022, male/female selection and male elimination must be brought to an embryonic status prior to the onset of nociception. The present study evaluated the ontogenetic point when noxious stimuli potentially could be perceived/processed in the brain in ovo. EEG-recordings from randomized hyperpallial brain sites were recorded in ovo and noxious stimuli were applied. Temporal and spectral analyses of the EEG were performed. The onset of physiological neuronal signals could be determined at developmental day 13. ERP/ERSP/ITC analysis did not reveal phase-locked nociceptive responses. Although no central nociceptive responses were documented, adequate EEG-responses to noxious stimuli from other brain areas cannot be excluded. The extreme stress impact on the embryo during the recording may overwrite the perception of noniceptive stimuli. The results suggest developmental day 13 as the earliest embryonal stage being able to receive and process nociceptive stimuli.

neuroscience↗

bioRxiv2020

Under-the-radar dengue virus infections in natural populations of Aedes aegypti mosquitoes

The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort on the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the metavirome of four populations of Ae. aegypti mosquitoes collected in 2016-2017 from Manatee County, Florida. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a two-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, as well as explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of these DENV4 infections in Ae. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. ImportanceSince 1999, dengue outbreaks in the continental United States (U.S.) involving local transmission have occurred episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from endemic countries. To date, the U.S. public health response to dengue outbreaks is largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of non-outbreak DENV4 transmission and maintenance within a local mosquito vector population in the continental U.S.in the absence of a human case during a two-year time period. Our data suggest that molecular surveillance of mosquito populations in high-risk, high tourism areas of the U.S., may allow for proactive, targeted vector control before potential arbovirus outbreaks.

ecology↗