Metal–organic framework–injectable hydrogel hybrid scaffolds promote accelerated angiogenesis for in vivo tissue engineering

The application of nanoscale metal-organic frameworks (MOFs) in tissue engineering is receiving increased attention. As three-dimensional scaffolding materials that provide an appropriate extracellular microenvironment supporting the survival, proliferation, and organization of cells play a key role in vivo tissue engineering, hybridization of nanoscale MOFs with bulk hydrogels has led to the development of nanoscale MOF-combined hydrogels. However, development of nanoscale MOF-combined hydrogel scaffolds remains challenging. Generally, since the gelation properties of injectable hydrogels are delicate, the sol-gel transition behavior could be lost due to the influence of additives. To date, little progress has been made in the development of nanoscale MOF-combined injectable hydrogel scaffolds. Herein, we propose a novel injectable hydrogel scaffold generated by combining NU-1000 nanoscale MOFs with PLGA-PEG-PLGA/LAPONITE® nanocomposite hydrogels. The resultant PLGA-PEG-PLGA/LAPONITE®/l-Arg@NU-1000 hybrid hydrogels exhibited sustained slow release of l-arginine over 1 month. The precursor solution of PLGA-PEG-PLGA/LAPONITE®/l-Arg@NU-1000 undergoes rapid sol-gel transition upon exposure to body temperature, enabling focal administration of the hydrogel at desired locations in the body via simple injection. The sustained l-arginine-slow release capability of the hybrid hydrogels results from the functionality of NU-1000 as a primary carrier and efficiently facilitates angiogenesis in vivo. The hybrid hydrogel exhibits highly specific functionality as a scaffold that cannot be achieved using NU-1000 alone or PLGA-PEG-PLGA/LAPONITE® hydrogels alone, thus indicating that the hybrid injectable hydrogels have the potential to become a new type of scaffold for tissue engineering.