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Poly(ethylene glycol)-peptide- and glycosaminoglycan-peptide conjugates obtained by a regio-selective amino acid protection strategy are converted into cell-instructive hydrogel matrices capable of inducing morphogenesis in embedded human vascular endothelial cells and dorsal root ganglia.

Angiogenesis, the outgrowth of blood vessels, is crucial in development, disease and regeneration. Studying angiogenesis in vitro remains challenging because the capillary morphogenesis of endothelial cells (ECs) is controlled by multiple exogenous signals. Therefore, a set of in situ-forming starPEG-heparin hydrogels was used to identify matrix parameters and cellular interactions that best support EC morphogenesis. We showed that a particular type of soft, matrix metalloproteinase-degradable hydrogel containing covalently bound integrin ligands and reversibly conjugated pro-angiogenic growth factors could boost the development of highly branched, interconnected, and lumenized endothelial capillary networks. Using these effective matrix conditions, 3D heterocellular interactions of ECs with different mural cells were demonstrated that enabled EC network modulation and maintenance of stable vascular capillaries over periods of about one month in vitro. The approach was also shown to permit in vitro tumor vascularization experiments with unprecedented levels of control over both ECs and tumor cells. In total, the introduced 3D hydrogel co-culture system could offer unique options for dissecting and adjusting biochemical, biophysical, and cell-cell triggers in tissue-related vascularization models.A ngiogenesis describes the outgrowth of new blood vessels and is a research 'hot spot' as emerging therapeutic opportunities for various different pathologic conditions directly relate to this widespread phenomenon. The formation of vascular sprouts is a complex multistep process including: (1) growth factor (GF) gradient formation, (2) endothelial cell (EC) activation, migration, and proliferation, (3) capillary development, and (4) stabilization by mural cells 1 . Studying the process of vascular sprout formation in vitro requires 3D models, which recapitulate the consecutive steps of capillary formation. Most angiogenesis research focuses on the biology of ECs, which are the core component of vascular structures. However, their activity in vivo is tightly regulated by supporting cell types such as pericytes and smooth muscle cells (SMCs) 2 indicating the importance of the often-neglected heterocellular interactions in in vitro models of angiogenesis. Isolated ECs preserve their vasculogenic and angiogenic characteristics in culture. When embedded in a suitable 3D scaffold, ECs temporarily form inter-connected tubular networks resembling vascular capillaries 3 , thus enabling in vitro vascular sprouting studies. Tissue-derived biopolymer matrices such as collagen 4-6 and fibrin 7,8 were shown to induce EC vascular morphogenesis successfully, and significantly contributed to our knowledge about angiogenesis, but their poor stability limits the development of defined, long term, in vitro assays. In search for improvement, synthetic polymer materials were systematically tested and studies using poly(ethylene glycol) (PEG) 9 and hyaluronic acid (HA) 10,11 based hydrogels demonstrated that EC capillary formation is str...

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Sponges are probably the earliest branching animals, and their fossil record dates back to the Precambrian. Identifying their skeletal structure and composition is thus a crucial step in improving our understanding of the early evolution of metazoans. Here, we present the discovery of 505–million-year-old chitin, found in exceptionally well preserved Vauxia gracilenta sponges from the Middle Cambrian Burgess Shale. Our new findings indicate that, given the right fossilization conditions, chitin is stable for much longer than previously suspected. The preservation of chitin in these fossils opens new avenues for research into other ancient fossil groups.

Bio-responsive polymer architectures can empower medical therapies by engaging molecular feedback-response mechanisms resembling the homeostatic adaptation of living tissues to varying environmental constraints. Here we show that a blood coagulation-responsive hydrogel system can deliver heparin in amounts triggered by the environmental levels of thrombin, the key enzyme of the coagulation cascade, which—in turn—becomes inactivated due to released heparin. The bio-responsive hydrogel quantitatively quenches blood coagulation over several hours in the presence of pro-coagulant stimuli and during repeated incubation with fresh, non-anticoagulated blood. These features enable the introduced material to provide sustainable, autoregulated anticoagulation, addressing a key challenge of many medical therapies. Beyond that, the explored concept may facilitate the development of materials that allow the effective and controlled application of drugs and biomolecules.

Reduction of complexity of the extracellular matrix (ECM) to a non-covalent structure with minimal chemically defined components represents an attractive avenue for understanding the biology of the ECM. The resulting system could lead to the design of tailor-made biomaterials that incorporate varying functionalities. Negatively charged glycos­amino­glycans are the major components of the ECM. Their interaction with positively charged proteins is important for dynamic three-dimensional scaffold formation and function. We designed and screened minimal peptide motifs whose conjugates with polyethylene glycol interact with heparin to form non-covalent hydrogels. Here we show the structure/function relationship of the (RA) n and (KA) n motifs and determined that both basic residues and the heparin-induced α-helix formation are important for the assembly process. Simple rules allowed us to tune various aspects of the matrix system such as the gelation rates, biodegradability, rheological properties, and biofunctionality. The hydrogels can encapsulate cells and support cell survival.

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