A novel biodegradable self-healing hydrogel to induce blood capillary formation

Abstract

A major challenge in tissue engineering is to generate a functional microvasculature that ensures proper blood perfusion and connection with surrounding tissues. Strategies such as the incorporation of growth factors have been proposed to induce the growth of new blood vessels into engineered tissue, but limitations remain. Herein a novel chitosan-fibrin (CF)-based self-healing hydrogel with a modulus of~1.2 kPa was developed. The self-healing hydrogel was found to be injectable and to degradẽ 70% in 2 weeks. Vascular endothelial cells seeded in the CF hydrogel were able to form capillary-like structures. Moreover, the injection of the CF hydrogel alone promoted angiogenesis in the perivitelline space of zebrafish and rescued the blood circulation in ischemic hindlimbs of mice. The excellent self-healing and angiogenic capacities of the hydrogel may be associated with the formation of an interpenetrating polymer network structure between chitosan and fibrin. This unique self-healing hydrogel offers new possibilities for future applications to vascular repair.

Biomaterial Substrate‐Mediated Multicellular Spheroid Formation and Their Applications in Tissue Engineering

“…For example, they could be transplanted with biomaterials into patients with limb ischemia or coronary artery disease to repair the damaged blood circulation system. A very recent study has explored that single dispersed ECs seeded in the chitosan‐fibrin‐based (CF) self‐healing hydrogel could grow into spheroids and form capillary‐like structures . In addition, the injection of the CF hydrogel alone could rescue the blood circulation in limb ischemic mice.…”

“…A very recent study has explored that single dispersed ECs seeded in the chitosan-fibrin-based (CF) self-healing hydrogel could grow into spheroids and form capillary-like structures. [61] In addition, the injection of the CF hydrogel alone could rescue the blood circulation in limb ischemic mice. Thus, the hydrogel which promotes the spheroid formation of ECs and tube formation may offer new possibilities for future applications to vascular repair.…”

A self-healing hydrogel as an injectable instructive carrier for cellular morphogenesis

“…These outcomes may be attributed to the lack of bio-functionality in the networks of current self-healing hydrogels, which is critical in cell-material interactions, cell responses and morphogenesis [44–48]. Most recently, Hsu’s group developed a composite self-healing hydrogel cross-linked by chitosan and formylbenzoic-functioned poly (ethylene glycol) [76]. The fibrin was introduced into the network to provide bio-functional sites for inducing blood capillary formation.…”

One-pot solvent exchange preparation of non-swellable, thermoplastic, stretchable and adhesive supramolecular hydrogels based on dual synergistic physical crosslinking

“…To improve the mechanical properties of chemically crosslinked hydrogels, researchers have developed ingenious strategies, including nanocomposite hydrogels, double-network hydrogels, hybrid crosslinking hydrogels and tetra-polyethylene glycol hydrogels. [14][15][16][17][18][19][20][21][22] Recently, increasing research attention has been dedicated to enhancing the mechanical performance of physically crosslinked supramolecular hydrogels. One recent study demonstrated very tough physical hydrogels composed of polyampholytes.…”