Decellularization of extracellular matrices offers an alternative source of regenerative biomaterials that preserve biochemical structure and matrix components of native tissues. In this study, decellularized bovine spinal cord meninges (dSCM)derived extracellular matrix hydrogel (MeninGEL) is fabricated by employing a protocol that involves physical, chemical, and enzymatic processing of spinal meninges tissue and preserves the biochemical structure of meninges. The success of decellularization is characterized by measuring the contents of residual DNA, glycosaminoglycans, and hydroxyproline, while a proteomics analysis is applied to reveal the composition of MeninGEL. Frequency and temperature sweep rheometry show that dSCM forms self-supporting hydrogel at physiological temperature. The MeninGEL possesses excellent cytocompatibility. Moreover, it is evidenced with immuno/histochemistry and gene expression studies that the hydrogel induces growth-factor free differentiation of human mesenchymal stem cells into neurallineage cells. Furthermore, MeninGEL instructs human umbilical vein endothelial cells to form vascular branching. With its innate bioactivity and low batch-to-batch variation property, the MeninGEL has the potential to be an off-the-shelf product in nerve tissue regeneration and restoration.

Abstract3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio‐instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio‐instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering. Herein, 3D printable and perfusable multicomponent hydrogel constructs with high elasticity, self‐recovery properties, excellent hydrodynamic performance, and improved bioactivity are reported. The materials' design strategy integrates fast gelation kinetics of sodium alginate (Alg), in situ crosslinking of tyramine‐modified hyaluronic acid (HAT), and temperature‐dependent self‐assembly and biological functions of decellularized aorta (dAECM). Using extrusion‐based printing approach, the capability to print the multicomponent hydrogel bioinks with high precision into a well‐defined vascular constructs able to withstand flow and repetitive cyclic compressive loading, is demonstrated. Both in vitro and pre‐clinical models are used to show the pro‐angiogenic and anti‐inflammatory properties of the multicomponent vascular constructs. This study presents a strategy to create new bioink whose functional properties are greater than the sum of their components and with potential applications in vascular tissue engineering and regenerative medicine.

Extracellular nanovesicles, particularly exosomes, can deliver their diverse bioactive biomolecular content, including miRNAs, proteins, and lipids, thus providing a context for investigating the capability of exosomes to induce stem cells toward lineage‐specific cells and tissue regeneration. In this study, it is demonstrated that rat subventricular zone neural stem cell‐derived exosomes (rSVZ‐NSCExo) can control neural‐lineage specification of human mesenchymal stem cells (hMSCs). Microarray analysis shows that the miRNA content of rSVZ‐NSCExo is a faithful representation of rSVZ tissue. Through immunocytochemistry, gene expression, and multi‐omics analyses, the capability to use rSVZ‐NSCExo to induce hMSCs into a neuroglial or neural stem cell phenotype and genotype in a temporal and dose‐dependent manner via multiple signaling pathways is demonstrated. The current study presents a new and innovative strategy to modulate hMSCs fate by harnessing the molecular content of exosomes, thus suggesting future opportunities for rSVZ‐NSCExo in nerve tissue regeneration.

A supramolecular hydrogel providing a biomimetic neural microenvironment with improved mechanical properties presents a laminin-derived neuro-inductive peptide epitope that induces multipotent stem cells into neural-lineage cells.

This work presents a polysaccharide and protein-based two-component hybrid hydrogel integrating the cell-adhesive gelatin-tyramine (G-Tyr) and nonadhesive hyaluronic acid-tyramine (HA-Tyr) through enzyme-mediated oxidative coupling reaction. The resulting HA-Tyr/G-Tyr hydrogel reflects the precise chemical and mechanical features of the cancer extracellular matrix and is able to tune cancer cell adhesion upon switching the component ratio. The cells form quasi-spheroids on HA-Tyr rich hydrogels, while they tend to form an invasive monolayer culture on G-Tyr rich hydrogels. The metastatic genotype of colorectal adenocarcinoma cells (HT-29) increases on G-Tyr rich hydrogels which is driven by the material's adhesive property, and additionally confirmed by the suppressed gene expressions of apoptosis and autophagy. On the other hand, HA-Tyr rich hydrogels lead the cells to necrotic death via oxidative stress in quasi-spheroids. This work demonstrates the ideality of HA-Tyr/G-Tyr to modulate cancer cell adhesion, which also has potential in preventing primary metastasis after onco-surgery, biomaterials-based cancer research, and drug testing.