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Granular hydrogels have evolved into an innovative technology for biomedicine. Unlike conventional hydrogels, granular hydrogels display dynamic properties like injectability and porosity, making them feasible for applications in 3D bioprinting and tissue engineering. High-energy electron irradiation combines sterilization and tuning of hydrogel properties without adding potentially cytotoxic chemicals. In this study, granular agarose/alginate hydrogels are prepared by electrospraying. Utilizing 10 MeV electron irradiation, the granular hydrogels are treated in a dose range of 0 kGy-30 kGy relevant for sterilization. Herein, a size reduction of the microparticles is observed. Mechanical properties of individual agarose/alginate beads are examined using AFM measurements revealing a gel softening attributed to radiation induced chain scission. Shear-thinning and self-healing characteristics of the entire granular hydrogel are studied employing rheology. Although viscoelasticity changes under irradiation, shear-thinning and self-healing prevails. These dynamic properties enable injection, which is demonstrated for 27 G needles. This study presents a mechanical characterization of high-energy electron irradiated granular agarose/alginate hydrogels that extends the diversity of available injectable hydrogels and provides a basis for biomedical applications of this scaffold.

Spatial control of mechanical properties of hydrogels such as gelatin is of high interest in order to develop highly functionalized substrates for applications in tissue engineering and biomedicine. Established methods to mechanically pattern hydrogels, including photolithography and ink-jet printing, employ additional reagents to induce changes in the network towards local differences in stiffness. Due to possible toxicity of these incorporated agents, reagent-free techniques are highly desirable for any biomedical field of application. Within the present work, we introduce a two-step process in which the focused electron beam of an electron beam lithography system is first utilized to obtain mechanical patterns in μm-range on air-dried gelatin substrates without any additional reagents. In a second step, these functionalized gelatin substrates are stabilized against gel-sol-transition for physiological conditions by global electron irradiation in the hydrated state by induction of polymer crosslinking. This work investigates precise mechanical patterning of gelatin obtained by this two-step functionalization process using first local and then global electron irradiation. Therefore, structural and mechanical characterization was performed by atomic force microscopy in the air-dried and rehydrated state. These qualitative and quantitative analyses show that excellent mechanical patterning of gelatin hydrogels can be achieved by the presented reagent-free two-step process. Keywords: Mechanical patterning, Hydrogels, Gelatin, Reagent-free, Electron irradiation

Due to their excellent biocompatibility and biodegradability, natural hydrogels are highly demanded biomaterials for biomedical applications such as wound dressing, tissue engineering, drug delivery or three dimensional cell culture. Highly energetic electron irradiation up to 10 MeV is a powerful and fast tool to sterilize and tailor the material's properties. In this study, electron radiation treatment of agarose hydrogels was investigated to evaluate radiation effects on physical, structural and chemical properties. The viscoelastic behavior, surface hydrophilicity and swelling behavior in a range of typical sterilization doses of 0 kGy to 30 kGy was analyzed. The mechanical properties were determined by rheology measurements and decreased by more than 20% compared to the initial moduli. The number average molecular weight between crosslinks was estimated based on rubber elasticity theory to judge on the radiation degradation. In this dose range, the number average molecular weight between crosslinks increased by more than 6%. Chemical structure was investigated by FTIR spectroscopy to evaluate the radiation resistance of agarose hydrogels. With increasing electron dose, an increasing amount of carbonyl containing species was observed. In addition, irradiation was accompanied by formation of gas cavities in the hydrogels. The gas products were specified for CO2, CO and H2O. Based on the radiolytic products, a radiolysis mechanism was proposed. Electron beam treatment under high pressure conditions was found to reduce gas cavity formation in the hydrogels.

Novel strategies to mimic mammalian extracellular matrix (ECM) in vitro are desirable to study cell behavior, diseases and new agents in drug delivery. Even though collagen represents the major constituent of mammalian ECM, artificial collagen hydrogels with characteristic tissue properties such as network size and stiffness are difficult to design without application of chemicals which might be even cytotoxic. In our study we investigate how high energy electron induced crosslinking can be utilized to precisely tune collagen properties for ECM model systems. Constituting a minimally invasive approach, collagen residues remain intact in the course of high energy electron treatment. Quantification of the 3D pore size of the collagen network as a function of irradiation dose shows an increase in density leading to decreased pore size. Rheological measurements indicate elevated storage and loss moduli correlating with an increase in crosslinking density. In addition, cell tests show well maintained viability of NIH 3T3 cells for irradiated collagen gels indicating excellent cellular acceptance. With this, our investigations demonstrate that electron beam crosslinked collagen matrices have a high potential as precisely tunable ECM-mimetic systems with excellent cytocompatibility. Keywords: Biomimetic collagen, Extracellular matrix model, Reagent-free crosslinking, High energy electron crosslinking

Design of functionalized biomimetic scaffolds is one of the key approaches for regenerative medicine and other biomedical applications. Development of engineered tissue should optimize organization and function of cells and tissue in vitro as well as in vivo. Surface topography is one factor controlling cellular behavior and tissue development. By topographical patterning of biocompatible materials, highly functionalized scaffolds can be developed. Gelatin is hereby a promising candidate due to its biocompatibility and biodegradability. It is low in cost and easy to handle, enabling a variety of applications in science and medicine. However, for biomedical applications at physiological conditions, gelatin has to be additionally stabilized since its gel-sol-transition temperature lies beneath the human body temperature. This is realized by a reagent-free cross-linking technique utilizing electron beam treatment. By topographical patterning, gelatin can be functionalized toward scaffolds for cell cultivation and tissue development. Thereby, customized patterns are transferred onto gelatin hydrogels via molds. Thermal stabilization of gelatin is then achieved by electron-induced cross-linking. In this study, we investigate the influence of gelatin concentration and irradiation dose on pattern transfer, long-term stability of topographically patterned gelatin hydrogels, and their impact on the cellular behavior of human umbilical vein endothelial cells as well as normal human dermal fibroblasts. We will show that contact guidance occurs for both cell types due to a concrete stripe pattern. In addition, the presented studies show a high degree of cytocompatibility, indicating a high potential of topographically patterned gelatin hydrogels as tissue development scaffold for prospective biomedical applications.

Smart materials such as stimuli responsive polymeric hydrogels offer unique possibilities for tissue engineering and regenerative medicine. As, however, most synthetic polymer systems and their degradation products lack complete biocompatibility and biodegradability, this study aims to synthesize a highly magnetic responsive hydrogel, based on the abundant natural biopolymer collagen. As the main component of vertebratal extracellular matrix, it reveals excellent biocompatibility. In combination with incorporated magnetic iron oxide nanoparticles, a novel smart nano-bio-ferrogel can be designed. While retaining its basic biophysical properties and interaction with living cells, this collagen-nanoparticle hydrogel can be compressed to 38% of its original size and recovers to 95% in suitable magnetic fields. Besides the phenomenology of this scenario, the underlying physical scenarios are also discussed within the framework of network models. The observed reversible peak strains as large as 150% open up possibilities for the fields of biomedical actuation, soft robotics and beyond.

Biomimetic materials with programmable stimuli responsiveness constitute a highly attractive material class for building bioactuators, sensors and active control elements in future biomedical applications. With this background, we demonstrate how energetic electron beams can be utilized to construct tailored stimuli responsive actuators for biomedical applications. Composed of collagen-derived gelatin, they reveal a mechanical response to hydration and changes in pH-value and ion concentration, while maintaining their excellent biocompatibility and biodegradability. While this is explicitly demonstrated by systematic characterizing an electron-beam synthesized gelatin-based actuator of cantilever geometry, the underlying materials processes are also discussed, based on the fundamental physical and chemical principles. When applied within classical electron beam lithography systems, these findings pave the way for a novel class of highly versatile integrated bioactuators from micro- to macroscales.

Zusammenfassung. Angeregt durch die Befunde der PISA-Studie und auf der Basis bisheriger Förderprogramme wurde das Lesetraining LekoLemo (Programm zur Förderung der LEseKOmpetenz und LEseMOtivation) für Schüler der 7. Jahrgangsstufe entwickelt. Das Training unterscheidet sich von bereits existierenden Lesetrainings vor allem durch zwei Aspekte: (1) Es umfasst Aufgaben zu den in der PISA-Studie verwendeten Dimensionen des Lesens Informationen ermitteln, textbezogenes Interpretieren sowie Reflektieren und Bewerten und (2) beinhaltet eine explizite Förderung der Lesemotivation. Die vorliegende Studie überprüfte das revidierte LekoLemo-Training anhand einer Stichprobe von 235 Siebtklässlern. Die Ergebnisse belegen die Wirksamkeit des Trainings und zeigen signifikante Effekte geringer bis mittlerer Größe auf die Lesekompetenz im Follow-up-Test. Demgegenüber erwiesen sich die Effekte auf die intrinsische Lesemotivation und das Selbstkonzept nicht nur als niedrig, sondern auch als nicht nachhaltig.