Thermoresponsive and Photocrosslinkable Poly(2-alkyl-2-oxazoline) Toolbox - Customizable Ultralow-Fouling Hydrogel Coatings for Blood Plasma Environments.

This study focuses on developing surface coatings with excellent antifouling properties, crucial for applications in the medical, biological, and technical fields, for materials and devices in direct contact with living tissues and bodily fluids such as blood. This approach combines thermoresponsive poly(2-alkyl-2-oxazoline)s, known for their inherent protein-repellent characteristics, with established antifouling motifs based on betaines. The polymer framework is constructed from various monomer types, including a novel benzophenone-modified 2-oxazoline for photocrosslinking and an azide-functionalized 2-oxazoline, allowing subsequent modification with alkyne-substituted antifouling motifs through copper(I)-catalyzed azide-alkyne cycloaddition. From these polymers surface-attached networks are created on benzophenone-modified gold substrates via photocrosslinking, resulting in hydrogel coatings with several micrometers thickness when swollen with aqueous media. Given that poly(2-alkyl-2-oxazoline)s can exhibit a lower critical solution temperature in water, their temperature-dependent solubility is compared to the swelling behavior of the surface-attached hydrogels upon thermal stimulation. The antifouling performance of these hydrogel coatings in contact with human blood plasma is further evaluated by surface plasmon resonance and optical waveguide spectroscopy. All surfaces demonstrate extremely low retention of blood plasma components, even with undiluted plasma. Notably, hydrogel layers with sulfobetaine moieties allow efficient penetration by plasma components, which can then be easily removed by rinsing with buffer.

Photocrosslinkable polysaccharide hydrogel composites based on dextran or pullulan-amylose blends with cytokines for a human co-culture model of human osteoblasts and endothelial cells.

Although a large body of research has been devoted to biomaterial development for bone tissue engineering and related medical disciplines in the last few years, novel and optimized materials especially for bone fractures of critical sizes demand continued development. In this respect, polysaccharide-based hydrogels demonstrate beneficial properties and fulfill the main requirements for a bone tissue scaffold as they are hydrophilic, biocompatible, and biodegradable. The aim of the present study was the development of a natural polysaccharide-based scaffold material that can integrate with the host tissue and support bone regeneration. For this purpose, we prepared and investigated two polymer hydrogel composites of photocrosslinkable derivatives of either pure dextran or a mixture of amylose and pullulan with varying composition. In order to increase their biological activity the swollen hydrogel matrices were compounded with stromal derived growth factor (SDF-1) and bone morphogenic protein (BMP-2). As skeletal development is known to depend on angiogenesis, these hydrogel systems were subjected to mono- and co-culture models of human primary osteoblasts (hOBs) with human endothelial cells (HUVEC - as precursors for blood vessel development). The effect of cytokines on hydrogel-dependent cell behavior was analyzed in the presence and absence of the growth factors SDF-1 and BMP-2. Both the employed cell types grew on all cytokine-modified hydrogel composites, which was assessed by optical microscopy and proliferation assays. Migration assays indicated enhanced HUVEC migration under the influence of SDF-1 and real-time PCR demonstrated an enhanced expression of cell-specific markers for growth factor-modified hydrogels, thus demonstrating their functional bioactivity. Our results demonstrate the fundamental potential of such multi-component polysaccharide hydrogel composites as biomaterials for bone regeneration.