Light-based 3D printing of oxygen-generating nanocomposite scaffolds accelerates bone regeneration

3D printed bone substitute scaffolds have emerged as a promising alternative to allografts and autografts which represent the current clinical gold standard for healing of critical size bone defects. However, the number one challenge that prevents them from being able to fully regenerate large scale bone tissue fragments is insufficient supply of oxygen within the defect site that creates localized regions of hypoxia which block sufficient cell migration and proliferation. This paper proposes the use of a Digital Light Processing 3D printed GelMA-PEGDA hydrogel scaffold, functionalized with oxygen-generating, CaO2 loaded, Hollow Silica nanoparticles, as an implantable bone substitute platform, for short term delivery of oxygen during the early stages of the bone regeneration process. The CaO2-Silica nP Platform for Osteogenic Development, COSnPPOD, are mechanically characterized and assessed using both an in vitro pre-osteoblast cell seeding and transwell coculture model, and an in vivo albino mouse calvarial model. The COSnPPOD system proved capable of short-term gradual oxygen release, supported by the synergistic effect of the porous geometry and the nP encapsulation, was determined to be biocompatible and non-cytotoxic through the in vitro model, and shown to promote osteogenesis with a significantly larger amount of new bone formation compared to free-healing defects and non-functionalized GelMA-PEGDA control scaffolds.