Injectable, In Situ Self-cross-linking, Self-healing Poly(l-glutamic acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering.

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of -CHO/-NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the hydrogels were examined. The PLGA/PEG hydrogels cross-linked by dynamic Schiff base linkages exhibited good self-healing ability. Additionally, the PLGA/PEG hydrogels had good biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and could effectively support BMSC proliferation and deposition of glycosaminoglycans and upregulate the expression of cartilage-specific genes. In a rat cartilage defect model, PLGA/PEG hydrogels significantly promoted new cartilage formation. The results suggest the prospect of the PLGA/PEG hydrogels in cartilage tissue engineering.

Mussel-Inspired Bisphosphonated Injectable Nanocomposite Hydrogels with Adhesive, Self-Healing, and Osteogenic Properties for Bone Regeneration.

Injectable hydrogels have received much attention because of the advantages of simulation of the natural extracellular matrix, microinvasive implantation, and filling and repairing of complex shape defects. Yet, for bone repair, the current injectable hydrogels have shown significant limitations such as the lack of tissue adhesion, deficiency of self-healing ability, and absence of osteogenic activity. Herein, a strategy to construct mussel-inspired bisphosphonated injectable nanocomposite hydrogels with adhesive, self-healing, and osteogenic properties is developed. The nano-hydroxyapatite/poly(l-glutamic acid)-dextran (nHA/PLGA-Dex) dually cross-linked (DC) injectable hydrogels are fabricated via Schiff base cross-linking and noncovalent nHA-BP chelation. The chelation between bisphosphonate ligands (alendronate sodium, BP) and nHA favors the uniform dispersion of the latter. Moreover, multiple adhesion ligands based on catechol motifs, BP, and aldehyde groups endow the hydrogels with good tissue adhesion. The hydrogels possess excellent biocompatibility and the introduction of BP and nHA both can effectively promote viability, proliferation, migration, and osteogenesis differentiation of MC3T3-E1 cells. The incorporation of BP groups and HA nanoparticles could also facilitate the angiogenic property of endothelial cells. The nHA/PLGA-Dex DC hydrogels exhibited considerable biocompatibility despite the presence of a certain degree of inflammatory response in the early stage. The successful healing of a rat cranial defect further proves the bone regeneration ability of nHA/PLGA-Dex DC injectable hydrogels. The developed tissue adhesive osteogenic injectable nHA/PLGA-Dex hydrogels show significant potential for bone regeneration application.

Injectable Maltodextrin-Based Micelle/Hydrogel Composites for Simvastatin-Controlled Release.

Injectable hydrogels have shown great potential in bone tissue engineering. Simvastatin (SIM), a common hypolipidemic drug, has been suggested as a potential agent to promote bone regeneration. However, due to its hydrophobic nature, the compatibility between SIM and hydrogels is rather poor, thereby greatly affecting the drug release behavior, the mechanical properties, and dimensional stability of the hydrogels. Herein, we presented a novel design to entrap SIM in an injectable maltodextrin-based micelle/hydrogel composite system. Maltodextrin-based micelles were prepared to solubilize and encapsulate SIM. The SIM-loaded aldehyde-modified micelles were anchored to the hydrogel network and served as a cross-linker to realize improved mechanical strength of hydrogel, controlled release, and osteogenic capability of SIM. In all, this study demonstrated a strategy to incorporate drug loaded carriers into hydrogels for drug delivery and tissue engineering applications.

Preparation of mussel-inspired injectable hydrogels based on dual-functionalized alginate with improved adhesive, self-healing, and mechanical properties.

Injectable hydrogels have aroused much attention for the advantages such as minimally invasive surgery, avoidance of surgical trauma, and filling and repairing irregularly shaped tissue defects. Mussel-inspired injectable hydrogels can be immobilized on the surface of tissues, resulting in stable biomaterial-tissue integration. However, the commonly used biomimetic mussel-inspired hydrogels are prepared by the oxidation of catechol groups, which involves the introduction or production of cytotoxic substances. Moreover, mussel-inspired hydrogels generally display weak mechanical strength and poor adhesiveness because of the consumption of catechol groups during oxidation. Herein, we described a strategy to prepare mussel-inspired injectable hydrogels via the Schiff base reaction. We grafted dopamine, an adhesive motif discovered in the holdfast pads of mussels, to aldehyde-modified alginate backbones. A series of injectable mussel-inspired adhesive, self-healing hydrogels were fabricated by in situ crosslinking of hydrazide-modified poly(l-glutamic acid) (PLGA-ADH) and dual-functionalized alginate (catechol- and aldehyde-modified alginate, ALG-CHO-Catechol). Also, oxidized ALG-CHO-Catechol hydrogels and PLGA/ALG-CHO hydrogels were prepared for comparison. The effects of the crosslinking method, catechol grafting ratio and solid content on the mechanical properties, self-healing behavior, adhesive properties, and hemostatic ability were investigated. Compared with the observations for oxidized ALG-CHO-Catechol hydrogels, more reasonable gelation time and notably enhanced mechanical properties and adhesive behavior were detected in the PLGA/ALG-CHO-Catechol hydrogel system. The PLGA/ALG-CHO-Catechol hydrogels also displayed clear self-healing ability and good cytocompatibility. The strong bioadhesion endowed the PLGA/ALG-CHO-Catechol hydrogels with superior hemostatic performance. These results suggested that PLGA/ALG-CHO-Catechol hydrogel might have great potential as an antibleeding and tissue repair material.