A tissue engineering approach to address craniofacial defects requires a biomaterial that balances macro-scale mechanical stiffness and strength with the micron-scale features that promote cell expansion and tissue biosynthesis. Such criteria are often in opposition, leading to suboptimal mechanical competence or bioactivity. We report the use of a multiscale composite biomaterial that integrates a polycaprolactone (PCL) reinforcement structure with a mineralized collagen-glycosaminoglycan scaffold to circumvent conventional tradeoffs between mechanics and bioactivity. The composite promotes activation of the canonical bone morphogenetic protein 2 (BMP-2) pathway and subsequent mineralization of adipose-derived stem cells in the absence of supplemental BMP-2 or osteogenic media. We subsequently examined new bone infill in the acellular composite, scaffold alone, or PCL support in 10 mm dia. ramus mandibular defects in Yorkshire pigs. We report an analytical approach to quantify radial, angular, and depth bone infill from micro-computed tomography data. The collagen-PCL composite showed improved overall infill, and significantly increased radial and angular bone infill versus the PCL cage alone. Bone infill was further enhanced in the composite for defects that penetrated the medullary cavity, suggesting recruitment of marrow-derived cells. These results indicate a multiscale mineralized collagen-PCL composite offers strategic advantages for regenerative repair of craniofacial bone defects.
Bibliographical noteFunding Information:
The authors would like to acknowledge the Carl R. Woese Institute for Genomic Biology for assistance with western blot analysis. Research reported in this publication was supported by the AO Foundation (Switzerland) as Project S-14-54H. The authors would like to thank Dr. Marcello Rubessa as well as Mr. Jonathon Mosley and the staff at the Imported Swine Research Laboratory (ISRL) for assistance with surgical procedures and animal care. This research was carried out in part at the Imaging Technology Group within the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign and the University of Illinois at Urbana-Champaign Veterinary Teaching Hospital. The authors would also like to thank Ms. Susan Hartman and Dr. Leilei Yin for assistance with live computed tomography and micro-computed tomography scans, respectively.
© Copyright 2018, Mary Ann Liebert, Inc.