Mechanical properties of hydrogels can be modified by the variation of structure and concentration of reactive building blocks. One promising biological source for the synthesis of biocompatible hydrogels is fibrinogen. Fibrinogen is a glycoprotein in blood, which can be transformed enzymatically to fibrin playing an important role in wound healing and clot formation. In the present work, it is demonstrated that hybrid hydrogels with their improved mechanical properties, tunable internal structure, and enhanced resistance to degradation can be synthesized by a combination of fibrinogen and reactive amphiphilic copolymers. Water‐soluble amphiphilic copolymers with tunable molecular weight and controlled amounts of reactive epoxy side groups are used as reactive crosslinkers to reinforce fibrin hydrogels. In the present work, copolymers that can influence the mechanical properties of fibrin‐based hydrogels are used. The reactive copolymers increase the storage modulus of the hydrogels from 600 Pa to 30 kPa. The thickness of fibrin fibers is regulated by the copolymer concentration. It could be demonstrated that the fibrin‐based hydrogels are biocompatible and support cell proliferation. Their degradation rate is considerably slower than that of native fibrin gels. In conclusion, fibrin‐based hydrogels with tunable elasticity and fiber thickness useful to direct cell responses like proliferation and differentiation are produced.

Angiogenesis, the formation of new blood vessels, is a fundamental process in both physiological repair mechanisms and pathological conditions, including cancer and chronic inflammation. Hydrogels are commonly used as in vitro models to mimic the extracellular matrix (ECM) and support endothelial cell behavior during angiogenesis. Mesenchymal stem cells further augment cell and tissue growth and are therefore widely used in regenerative medicine. Here we examined the combination of distinct hydrogel types—fibrin, collagen, and human platelet lysate (HPL)—on the formation of capillaries in a co-culture system containing human umbilical vein endothelial cells (HUVECs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The mechanical properties and structural changes of the hydrogels were characterized through scanning electron microscopy (SEM) and nanoindentation over 10 days. Fibrin and HPL gels sustained complex network formations, with HPL gels promoting even vascular tube formation of up to 10-fold capillary caliber. Collagen gels supported negligible angiogenesis. Our results suggest that HPL gels in combination with MSC-EC co-culture may be employed to obtain robust vascularization in tissue engineering. This study provides a comparative analysis of fibrin, collagen, and HPL hydrogels, focusing on their ability to support angiogenesis under identical conditions. Our findings demonstrate the superior performance of HPL gels in promoting robust vascular structures, highlighting their potential as a versatile tool for in vitro angiogenesis modeling.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of Hepatocyte Growth Factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF’s regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF’s long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold–cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF’s bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche, thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improved the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial’s suitability for in vitro pre-vascularization of biohybrid implants.

Cytocompatibility and hemocompatibility are essential features for tissue- and blood-contacting implants such as artificial heart valves, vascular grafts and stents. Platelet activation as the main trigger of thrombosis results in implant failures. The purpose of this study results from the demands on anti-coagulant and non-corrosive innovative biomaterials for cardiovascular implants. Therefore, hemocompatibility and cytocompatibility of various high-strength ceramics, such as alumina, zirconia, silicon nitride and silicon carbide, were examined to identify the most appropriate ceramic for cardiovascular implants. In addition to the material species, different crystallographic structures (single- and poly-crystalline) and surface terminations (Si and C faces) of silicon carbide were used in order to reveal the interactions between blood and material surface. Three cell types, i.e. human umbilical vein endothelial cells, mesenchymal stem cells and blood cells, were cultured on the substrates and their interactions with material surfaces were analyzed. Cytotoxicity of the materials was tested by live/dead staining. Hemocompatibility in terms of platelet and white blood cell activation was examined via scanning electron microscopy and indirect ELISA. To mimic physiological conditions in vitro, the hemocompatibility of the materials was additionally analyzed in a bioreactor under dynamic flow conditions in comparison to static incubation. All ceramics were found to be cytocompatible for mesenchymal stem cells, human umbilical vein endothelial cells and blood cells. The highest number of resting, non-activated platelets was observed on the monocrystalline silicon carbide demonstrating that this material triggers the platelet activation less compared to the other materials. It is found to be the most appropriate ceramic for blood-contacting implants in terms of cell adhesion, cell viability, and hemocompatibility.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improve the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical-dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.