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

Abstract

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.