Magnesium-organic framework-based stimuli-responsive systems that optimize the bone microenvironment for enhanced bone regeneration

Biomaterials that could synchronize with complex tissue physiological healing processes would have significant potential in bioengineering applications. Inspired by the "scatter shot" pattern in the embryonal intramembranous ossification process, a multifunctionalized scaffold is proposed to provide multiple osteogenic nucleation sites for bone regeneration multicellular unit (BRMU). First, an inherently therapeutic nanoplatform was fabricated that is composed of a gallic-acid-magnesium-based metal-organic frameworks (Mg-MOF) core and a biodegradable calcium phosphate (CaP) shell. The obtained MOF@CaP can be used for efficient bioactive factor protection and can mimic the physiological inflammation resolution response through the release of the inflammatory microenvironment (low pH) stimuli-responsive IL4. In addition, the MOF@CaP nanoplatform can provide a preferable repair microenvironment, such as by supplying magnesium for angiogenesis, gallic acid for reactive oxygen species removal, and calcium and phosphate to ensure that the extracellular bone matrix is calcified. Subsequently, IL4-MOF@CaP served as the discrete core of the bone islands by BRMU, was incorporated into collagen (Col) scaffolds to fabricate a multifunctional biodegradable scaffold. Remarkable in vivo functional bone regeneration was achieved with an in situ bone island pattern formed internally. Thus, the biomaterials replicating the developmental process can be an attractive strategy for enhancing tissue regeneration.