Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu

Type II diabetes mellitus (TIIDM) remains a challenging clinical issue for both dentists and orthopedists. By virtue of persistent hyperglycemia and altered host metabolism, the pathologic diabetic micromilieu with chronic inflammation, advanced glycation end products accumulation, and attenuated biomineralization severely impairs bone regeneration efficiency. Aiming to remodel the pathologic diabetic micromilieu, we 3D-printed bioscaffolds composed of Sr-containing mesoporous bioactive glass nanoparticles (Sr-MBGNs) and gelatin methacrylate (GelMA). Sr-MBGNs act as a biomineralization precursor embedded in the GelMA-simulated extracellular matrix and release Sr, Ca, and Si ions enhancing osteogenic, angiogenic, and immunomodulatory properties. In addition to angiogenic and anti-inflammatory outcomes, this innovative design reveals that the nanocomposites can modulate extracellular matrix reconstruction and simulate biomineralization by activating lysyl oxidase to form healthy enzymatic crosslinked collagen, promoting cell focal adhesion, modulating oste-oblast differentiation, and boosting the release of OCN, the noncollagenous proteins (intrafibrillar mineralization dependent), and thus orchestrating osteogenesis through the Kindlin-2/PTH1R/OCN axis. This 3D-printed bio-scaffold provides a multifunctional biomineralization-inspired system that remodels the barren diabetic microenvironment and sheds light on the new bone regeneration approaches for TIIDM.

Automated summary

Type II diabetes mellitus (TIIDM) poses challenges for dentists and orthopedists, but 3D-printed bioscaffolds containing Sr-MBGNs and GelMA can remodel the diabetic microenvironment, enhance bone regeneration, and promote osteogenic, angiogenic, and immunomodulatory properties through the release of Sr, Ca, and Si ions.