In situ bioprinting of high-density cell-laden core-shell microgel bioinks enabling cellular condensation for vascularized bone tissue regeneration

The project addresses the need for innovative therapeutic approaches for craniofacial bone regeneration in military personnel and veterans, overcoming challenges of traditional scaffold-based strategies. It proposes an immediately implantable, biodegradable, and photocrosslinkable high-density hMSC-laden core-shell microgel system that enables cell condensations and functional tissue generation in vivo. This system, combined with 3D bioprinting, allows for precise engineering of osteogenic cell condensations and spatially patterned prevascular networks. The rapid degradation of the microgel shell will facilitate fusion of condensations and integration with host tissue, driven by locally delivered growth factors. The hypothesis is that multi-tissue cell condensations can be fabricated directly in vivo for patterned prevascularized bone constructs. Specific aims include: (1) examining the role of physical properties and printing parameters on resolution and shape fidelity, (2) engineering and evaluating 3D bioprinted prevasculature patterned high cell-density bone constructs, and (3) determining the preclinical potential of these constructs to heal critical-sized rat calvarial bone defects.