Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue-interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue.

Eph receptors and their ephrin ligands were identified in the late 1980's. Subsequently, they were linked to different physiological and pathophysiological processes like embryonic development, angiogenesis, and tumorigenesis. In this regard, recent work focused on the distribution and effects of Eph receptors and ephrins on tumor cells and tumor microenvironment. The purpose of this review is to outline the role of these molecules in physiological angiogenesis and pathophysiological tumor angiogenesis. Furthermore, novel therapeutical approaches are discussed as Eph receptors and ephrins represent attractive targets for antiangiogenic therapy.

Bone defects of critical size after compound fractures, infections, or tumor resections are a challenge in treatment. Particularly, this applies to bone defects in patients with impaired bone healing due to frequently occurring metabolic diseases (above all diabetes mellitus and osteoporosis), chronic inflammation, and cancer. Adjuvant therapeutic agents such as recombinant growth factors, lipid mediators, antibiotics, antiphlogistics, and proangiogenics as well as other promising anti-resorptive and anabolic molecules contribute to improving bone healing in these disorders, especially when they are released in a targeted and controlled manner during crucial bone healing phases. In this regard, the development of smart biocompatible and biostable polymers such as implant coatings, scaffolds, or particle-based materials for drug release is crucial. Innovative chemical, physico- and biochemical approaches for controlled tailor-made degradation or the stimulus-responsive release of substances from these materials, and more, are advantageous. In this review, we discuss current developments, progress, but also pitfalls and setbacks of such approaches in supporting or controlling bone healing. The focus is on the critical evaluation of recent preclinical studies investigating different carrier systems, dual- or co-delivery systems as well as triggered- or targeted delivery systems for release of a panoply of drugs.

Eph receptor tyrosine kinases, particularly EphA2 and EphB4, represent promising candidates for molecular imaging due to their essential role in cancer progression and therapy resistance. Xanthine derivatives were identified to be potent Eph receptor inhibitors with IC₅₀ values in the low nanomolar range (1–40 nm). These compounds occupy the hydrophobic pocket of the ATP-binding site in the kinase domain. Based on lead compound 1, we designed two fluorine-18-labelled receptor tyrosine kinase inhibitors ([¹⁸F]2/3) as potential tracers for positron emission tomography (PET). Docking into the ATP-binding site allowed us to find the best position for radiolabelling. The replacement of the methyl group at the uracil residue ([¹⁸F]3) rather than the methyl group of the phenoxy moiety ([¹⁸F]2) by a fluoropropyl group was predicted to preserve the affinity of the lead compound 1. Herein, we point out a synthesis route to [¹⁸F]2 and [¹⁸F]3 and the respective tosylate precursors as well as a labelling procedure to insert fluorine-18. After radiolabelling, both radiotracers were obtained in approximately 5% radiochemical yield with high radiochemical purity (>98%) and a molar activity of >10 GBq μmol⁻¹. In line with the docking studies, first cell experiments revealed specific, time-dependent binding and uptake of [¹⁸F]3 to EphA2 and EphB4-overexpressing A375 human melanoma cells, whereas [¹⁸F]2 did not accumulate at these cells. Since both tracers [¹⁸F]3 and [¹⁸F]2 are stable in rat blood, the novel radiotracers might be suitable for in vivo molecular imaging of Eph receptors with PET.