Large segmental defects of the facial skeleton represent a series of operative and restorative challenges. Current reconstructive techniques, whether autologous bone, allogeneic bone, or prosthetic implant, are often limited by bone supply, infection, extrusion, and donor site morbidity. Adam Terella, MD, and colleagues investigated the in vivo osteogenic capabilities of a protease-sensitive polyethylene glycol scaffold in the healing of critical-size calvarial defects in the rat model. The authors use microcomputed tomography at intervals of 1, 4, and 8 weeks after implantation and assess bone formation across various implant types and control groups. A statistically significant reduction in calvarial wound size, from 50% (in the control group) to 77% (in the polyethylene glycol–matrix metalloproteinase–treated group), was observed in this animal series.