RT Journal Article SR Electronic T1 Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.19.440506 DO 10.1101/2021.04.19.440506 A1 Marley J. Dewey A1 Derek J. Milner A1 Daniel Weisgerber A1 Colleen L. Flanagan A1 Marcello Rubessa A1 Sammi Lotti A1 Kathryn M. Polkoff A1 Sarah Crotts A1 Scott J. Hollister A1 Matthew B. Wheeler A1 Brendan A.C. Harley YR 2021 UL http://biorxiv.org/content/early/2021/04/20/2021.04.19.440506.abstract AB Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.Competing Interest StatementThe authors have declared no competing interest.