4D printed hydrogel scaffold with swelling-stiffening properties and programmable deformation for minimally invasive implantation.

The power of three-dimensional printing in designing personalized scaffolds with precise dimensions and properties is well-known. However, minimally invasive implantation of complex scaffolds is still challenging. Here, we develop amphiphilic dynamic thermoset polyurethanes catering for multi-material four-dimensional printing to fabricate supportive scaffolds with body temperature-triggered shape memory and water-triggered programmable deformation. Shape memory effect enables the two-dimensional printed pattern to be fixed into temporary one-dimensional shape, facilitating transcatheter delivery. Upon implantation, the body temperature triggers shape recovery of the one-dimensional shape to its original two-dimensional pattern. After swelling, the hydrated pattern undergoes programmable morphing into the desired three-dimensional structure because of swelling mismatch. The structure exhibits unusual soft-to-stiff transition due to the water-driven microphase separation formed between hydrophilic and hydrophobic chain segments. The integration of shape memory, programmable deformability, and swelling-stiffening properties makes the developed dynamic thermoset polyurethanes promising supportive void-filling scaffold materials for minimally invasive implantation.

The regulatory role of sulfated polysaccharides in facilitating rhBMP-2-induced osteogenesis.

Sulfated polysaccharides have received much attention in recent years due to their special biological activities, especially the regulation of the biological activity of growth factors such as the representative inductive growth factor recombinant human bone morphogenetic protein-2 (rhBMP-2). However, the regulatory mechanisms from the aspect of the molecular chain structure have rarely been reported. In this article, we selected three kinds of sulfonates containing different backbone structures and functional groups, 2-N,6-O-sulfated chitosan (26 SCS), sulfated dextran (DSS) and poly(sodium-p-styrenesulfonate) (PSS), to explore the interaction between them and rhBMP-2. From in vivo and in vitro osteogenesis-related experiments, 26 SCS showed the best promoting effect on rhBMP-2 induced osteogenic differentiation and the sulfated amino group in 26 SCS could specifically bind to rhBMP-2. These findings indicated that the polysaccharide chain structure was a prerequisite for the synergy effect between 26 SCS and rhBMP-2; the effective combination of -SO3- and rhBMP-2 was an important factor in protecting the bioactivity of rhBMP-2. In addition, the presence of the sulfated amino group was the key factor in the specific binding between 26 SCS and rhBMP-2 and provided the possibility of capturing factors in vivo.

Construction of cytokine reservoirs based on sulfated chitosan hydrogels for the capturing of VEGF in situ.

Nutrients and oxygen are delivered mainly by blood vessels to nourish the cells and tissues in the body. Thus, biomaterials are processed by loading cytokines, such as vascular endothelial growth factors (VEGF), to facilitate angiogenesis in order to accelerate tissue regeneration. Nevertheless, the unpredictable biosecurity of exogenous cytokines is still a controversial issue for its clinical application. In this study, we constructed a kind of cytokine reservoir utilizing the binding affinity between heparin-like sulfate polysaccharide and endogenous growth factors. Two types of sulfated chitosan hydrogels, namely 6-O-sulfated chitosan (6-O-SCS) and 2-N,6-O-sulfated chitosan (2-N,6-O-SCS) hydrogels, were formed on the surface of the gelatin sponge matrix. The microstructure of the SCS-coated scaffolds is porous and interconnected, which is beneficial for cellular infiltration. Besides, human umbilical vein endothelial cells (HUVECs) can adhere and proliferate well on the surface of the scaffolds. Notably, sulfated chitosan-coated scaffolds exhibit an ability to capture VEGF in vitro & vivo, especially for the 2-N,6-O-SCS-coated scaffold. It is also verified by mice models that sulfated chitosan-coated scaffolds result in a concentrated VEGF microenvironment in specific domains as cytokine reservoirs and induce mass microvessels after implantation into subcutaneous tissues. As such, the sulfated chitosan-coated scaffolds served as VEGF reservoirs to accelerate angiogenesis and wound healing. This beneficial strategy may be applicable to in situ tissue regeneration by capturing more cytokines and promoting healing.