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Radecker, N.

Publications and source records attributed to Radecker, N..

9 recordsLinked to original sources

Residual Hair Biomaterial Particulates Improve Dermal Regeneration and Combined with Electrical Stimulation Accelerates Skin Wound Closure

ObjectiveTo evaluate the effect of residual hair (RH) biomaterial particulates, biphasic electrical stimulation (ES), and their combination (RHES) on the kinetics and quality of skin wound healing. MethodEighteen adult albino mice received bilateral, splinted 10-mm full-thickness dorsal excisional wounds and were randomly assigned to one of three animal groups producing four wound-level treatment conditions: untreated control (-) (n = 12), RH (n = 12), ES (n = 6), and combined RHES (n = 6 wounds). Daily wound images were segmented using an AI-assisted workflow: a U-Net (ResNet34 encoder, ImageNet-pretrained, trained on a parallel single-expert tracing study with held-out validation Dice = 0.906) generated initial boundary predictions, each reviewed and corrected as needed. Wound size measures (perimeter, area, equivalent diameter [D_eq], circularity, aspect ratio) were normalized to the day-0 value of each wound and analyzed by linear mixed-effects regression with mouse identity as a random intercept and mouse body weight as a covariate. On day 7, wounds were excised, fixed, processed for histology, and analyzed by Massons trichrome (collagen content in granulation tissue) and GAP-43 immunohistochemistry (a marker of regenerative cellular activity). ResultsAll three treatments significantly accelerated wound closure compared to (-) (Day x Treatment interaction {chi}2(3) = 36.4, ***p < 0.0001). The closure-rate advantages on the log-D_eq scale were ES - 0.047/day (***p < 0.0001), RHES -0.029/day (***p = 0.0005), and RH -0.022/day (**p = 0.0015). By day 7, mean D_eq had decreased to 0.58 of the day-0 value in ES, 0.69 in RHES, 0.73 in RH, and 0.79 in (-). Tissue analyses revealed treatment-specific differences in healing quality: RH and RHES wounds contained 6.1x and 8.5x more collagen in granulation tissue than (-) (both **p = 0.002 vs (-); both **p = 0.009 vs ES), and showed approximately 16x and 27x greater mean GAP-43 expression than (-), respectively; the RHES increase remained significant after Bonferroni correction (adjusted *p = 0.042), whereas the RH increase did not (adjusted p = 0.058). ES alone did not significantly increase either collagen content or GAP-43 expression. Wound shape was more circular and more stable across days in RH-containing groups. Mouse body weight did not predict closure, whereas image-derived dryness, eschar coverage, and wound contraction were significant negative predictors of measured wound size. ConclusionES, RH, and RHES each significantly improve wound closure kinetics. The improvement appears mechanistically distinct: ES principally accelerates closure rate, while RH principally enhances tissue-level regenerative markers (collagen deposition and GAP-43 expression). RHES combines both advantages. Declaration of interestDr. de Guzman is the inventor on a pending patent covering residual hair biomaterial methods and use and a provisional patent on powderized version, both owned by Hofstra University, and is the founder of a company developing wound care products based on the technology. The study was conducted independently. Data are available upon reasonable request.

bioengineering↗

Intramuscular Delivery of BMP-2 and Increasing Doses of LECT-1 Using Keratin-PEG Gels for Ectopic Tissue Differentiation

Producing bone and cartilage in a controlled and localized manner remains a significant challenge in regenerative medicine. This study investigated the ability of keratin- and polyethylene glycol (PEG)-based degradable hydrogels to deliver bone morphogenetic protein 2 (BMP-2) and leukocyte cell-derived chemotaxin 1 (LECT-1; also known as chondromodulin-1) intramuscularly to induce ectopic tissue formation. Adult male CD-1 mice received intramuscular implants of keratin-PEG gels containing a fixed dose of BMP-2 and increasing amounts of LECT-1. After two weeks, implants and surrounding muscle were analyzed using computed tomography (CT) and histology. The results showed that BMP-2 is necessary for forming new bone and cartilage, whereas LECT-1 alone appeared to trigger muscle dedifferentiation without ossification or chondrogenesis. Co-delivery of BMP-2 and LECT-1 enhanced bone and cartilage formation in a dose-dependent manner: higher LECT-1 doses led to proportionally more ectopic cartilage (linear correlation, r2 {approx} 90%), while bone formation peaked at the third LECT-1 dose at approximately twice the volume of the BMP-2-only group. These findings indicate that muscle-resident cells may be capable of reverting and switching to mesenchymal lineages, recapitulating endochondral ossification. The platform offers a promising strategy for growing bone and cartilage autografts within skeletal muscle bundles. Impact StatementThis study presents a novel strategy for inducing ectopic bone and cartilage formation by delivering BMP-2 and LECT-1 from keratin-PEG hydrogels into skeletal muscle. The findings suggest that muscle-resident cells can dedifferentiate and transdifferentiate into mesenchymal lineages, enabling controlled ectopic tissue regeneration. This approach may inform future tissue engineering therapies in which autografts are harvested from within the body, using skeletal muscle as an in vivo tissue incubator.

bioengineering↗

Chilling injury to algal symbionts induces host starvation and metabolic reorganization in a temperate cnidarian

Global temperature anomalies increasingly disrupt the cnidarian-algal symbiosis through a phenomenon termed bleaching. In contrast to heat stress, the mechanisms underlying symbiotic breakdown under cold stress remain largely unknown. Combining physiological and metabolomic measurements, we investigated the response of the photosymbiotic sea anemone holobiont Aiptasia couchii to an experiment mimicking a cold spell in the Mediterranean Sea. Within four weeks, we observed the onset of symbiotic breakdown reflected in reduced algal endosymbiont density and chlorophyll a content. While photosynthetic efficiency remained largely unaffected, no gross photosynthesis was detectable in cold-stressed anemones and decreases in glycosyldiacylglycerols and fatty acyl glycosides indicated chloroplast lipid remobilization. This breakdown of symbiotic carbon cycling was reflected in increased dipeptide and ceramide levels suggesting anemones catabolized protein reserves and induced pre-apoptotic pathways. Taken together, these responses suggest a decoupling of light and dark reactions of photosynthesis in cold-stressed endosymbionts, resembling chilling injury in higher plants and free-living microalgae. This chilling-induced collapse of symbiotic nutrient cycling eventually leads to host starvation in cold-stressed Cnidaria. Hence, while cold and heat stress may invoke contrasting physiological effects on endosymbionts, our results suggest that both stressors destabilize the symbiosis through similar mechanisms culminating in host starvation.

ecology↗

Biocompatibility of KAPs-Depleted Residual Hair

This work is an in-depth investigation of the in vitro and in vivo biocompatibility of processed and treated residual human hair samples with intact cuticle layers. The specimens included oxidized hair with no melanin (BLH) and hair with medium-(M-KAP) and low-(L-KAP) levels of keratin associated proteins (KAPs), confirmed through gel electrophoresis, electron microscopy, and trichrome histological staining, in comparison to the untreated regular hair (REG) control. All hair groups, high KAPs (H-KAPs: REG and BLH), M-KAP, and L-KAP, were found to be non-cytotoxic in the adipose fibroblast cell lines response to their extracts based on the ISO 10993-5 medical device biomaterial testing standard. In vivo mouse subcutaneous implantation (ISO 10993-6, local effects) at 2 weeks showed that the samples caused a foreign body response (FBR) with a thin fibrous encapsulation at a mean value of 28% relative skin dermis thickness; but notably, the L-KAP implant mitigated a statistically significant decrease in FBR area compared to H-KAPs (REG and/or BLH) and a lower number of cells, including immune cells of mostly macrophages and mast cells on the biomaterials surface, normalized to implant and tissue coverage. In the bulk of the capsules, blood vessels and collagen extracellular matrix densities were similar among groups. These findings suggest that small globular KAPs diffuse out of the cortex to the host-biomaterial interface which induce a slightly elevated FBR but limited to the implants surface vicinity. On-going follow-up research focuses on purer keratin-based macromolecularly organized residual hair biomaterials, those with depleted KAPs, for drug-delivery gel implants as they are deemed the most biocompatible. Statement of SignificanceHuman hair is an abundant biological product that is regularly discarded and wasted but has the potential to be a clinical implantable allograft biomaterial. There are currently just two FDA class II-510(k)-approved medical devices from hair, limited to surface / skin wound care use, and no class III-PMA or biologics-BLA implants. Also, these products and those in research and development phases are based on soluble keratin and KAPs extracts utilizing tedious processing conditions and requiring oxidation reaction for reassembly into gels and scaffolds. Here we describe that the insoluble residual hair biomaterials with organized keratin structure, higher-degree of disulfide crosslinks, and particularly those with depleted KAPs have increased biocompatibility based on pre-clinical ISO 10993 standards. This novel natural biomaterials are now being developed as drug-delivery implantable gels for clinical applications.

bioengineering↗

Symbiotic nutrient exchange enhances the long-term survival of cassiosomes, the autonomous stinging-cell structures of Cassiopea

Medusae of the widely distributed and locally invasive upside-down jellyfish Cassiopea release autonomous, mobile stinging structures. These so-called cassiosomes are a major contributor to contactless stinging incidents in (sub-)tropical shallow waters. While the presence of endosymbiotic dinoflagellates in cassiosomes has previously been observed, their potential contribution to the metabolism and long-term survival of cassiosomes is unknown. Combining stable isotope labeling and correlative SEM and NanoSIMS imaging with a long-term in vitro experiment, this study reveals a mutualistic symbiosis based on nutritional exchanges in dinoflagellate-bearing cassiosomes. We were able to show that organic carbon input from the dinoflagellates fuels the metabolism of the host tissue and enables anabolic nitrogen assimilation. Thanks to this symbiotic nutrient exchange, cassiosomes showed enhanced survival in the light compared to dark conditions for at least one month in vitro. Overall, this study demonstrates that cassiosomes, in analogy with Cassiopea medusae, are photosymbiotic holobionts. Cassiosomes thus promise to be a powerful new miniaturized model system for in-depth ultrastructural and molecular investigation of cnidarian photosymbioses.

ecology↗

Host starvation and in hospite degradation of algal symbionts shape the heat stress response of the Cassiopea-Symbiodiniaceae symbiosis

Global warming is causing large-scale disruption of cnidarian-Symbiodiniaceae symbioses fundamental to major marine ecosystems, such as coral reefs. However, the mechanisms by which heat stress perturbs these symbiotic partnerships remain poorly understood. In this context, the upside-down jellyfish Cassiopea has emerged as a powerful experimental model system. We combined a controlled heat stress experiment with isotope labeling and correlative SEM-NanoSIMS imaging to show that host starvation is a central component in the chain of events that ultimately leads to the collapse of the Cassiopea holobiont. Heat stress caused an increase in catabolic activity and a depletion of carbon reserves in the unfed host, concurrent with a reduction in the supply of photosynthates from its algal symbionts. This state of host starvation was accompanied by pronounced in hospite degradation of algal symbionts, which may be a distinct feature of the heat stress response of Cassiopea. Interestingly, this loss of symbionts by degradation was to a large extent concealed by body shrinkage of the starving animals, resulting in what could be referred to as invisible bleaching. Overall, our study highlights the importance of the nutritional status in the heat stress response of the Cassiopea holobiont. Compared with other symbiotic cnidarians, the large mesoglea of Cassiopea, with its structural sugar and protein content, may constitute an energy reservoir capable of delaying starvation. It seems plausible that this anatomical feature at least partly contributes to the relatively high stress tolerance of these animals in our warming oceans.

ecology↗

Symbiotic nutrient cycling enables the long-term survival of Aiptasia in the absence of heterotrophic food sources

Phototrophic Cnidaria are mixotrophic organisms that can complement their heterotrophic diet with nutrients assimilated by their algal endosymbionts. Metabolic models suggest that the translocation of photosynthates and their derivatives from the algae may be sufficient to cover the metabolic energy demands of the host. However, the importance of heterotrophy to the nutritional budget of these holobionts remains unclear. Here, we report on the long-term survival of the photosymbiotic anemone Aiptasia in the absence of heterotrophic food sources. Following one year of heterotrophic starvation, these anemones remained fully viable but showed an 85 % reduction in biomass compared to their regularly fed counterparts. This shrinking was accompanied by a reduction in host protein content and algal density, indicative of severe nitrogen limitation. Nonetheless, isotopic labeling experiments combined with NanoSIMS imaging revealed that the contribution of algal-derived nutrients to the host metabolism remained unaffected due to an increase in algal photosynthesis and more efficient carbon translocation. Taken together, our results suggest that, on a one- year timescale, heterotrophic feeding is not essential to fulfilling the energy requirements of the holobiont. But, while symbiotic nutrient cycling effectively retains carbon in the holobiont over long time scales, our data suggest that heterotrophic feeding is a critical source of nitrogen required for holobiont growth under oligotrophic conditions.

ecology↗

Coupled carbon and nitrogen cycling regulates the cnidarian-algal symbiosis

Efficient nutrient recycling underpins the ecological success of the cnidarian-algal symbiosis in oligotrophic waters. In a stable symbiosis, nitrogen limitation restricts the growth of algal endosymbionts and stimulates their release of photosynthates to the cnidarian animal host. However, the detailed mechanisms controlling nitrogen availability in hospite and their role in symbiosis regulation remain poorly understood. Here, we studied the metabolic regulation of symbiotic nitrogen cycling in the sea anemone Aiptasia by experimentally altering labile carbon availability in a series of experiments. Combining 13C and 15N stable isotope labeling experiments with physiological analyses and NanoSIMS imaging, we show that the competition for environmental ammonium between the host and its algal symbionts is regulated by labile carbon availability. Light regimes optimal for algal photosynthesis increased carbon availability in the holobiont and stimulated nitrogen assimilation in the host metabolism. Consequently, algal symbiont densities were lowest under optimal environmental conditions and increased toward the symbiosiss lower and upper light tolerance limits. This metabolic regulation promotes efficient carbon recycling in a stable symbiosis across a wide range of environmental conditions. At the same time, the dependence on resource competition may favor parasitic interactions explaining the instability of the symbiosis as the environmental conditions in the Anthropocene shift towards its tolerance limits.

ecology↗

Molecular insights into the Darwin paradox of coral reefs from the sea anemone Aiptasia

Symbiotic cnidarians such as corals and anemones form highly productive and biodiverse coral-reef ecosystems in nutrient-poor ocean environments, a phenomenon known as Darwins Paradox. Resolving this paradox requires elucidating the molecular bases of efficient nutrient distribution and recycling in the cnidarian-dinoflagellate symbiosis. Using the sea anemone Aiptasia, we show that during symbiosis, the increased availability of glucose and the presence of the algae jointly induce the coordinated upregulation and re-localization of glucose and ammonium transporters. These molecular responses are critical to support symbiont functioning and organism-wide nitrogen assimilation through GS/GOGAT-mediated amino-acid biosynthesis. Our results reveal crucial aspects of the molecular mechanisms underlying nitrogen conservation and recycling in these organisms that allow them to thrive in the nitrogen-poor ocean environments. One-sentence summaryWhole-organism nitrogen assimilation fueled by glucose from symbiotic algae enables corals to flourish in oligotrophic waters.

molecular biology↗