3D-Printed Demineralized Bone Matrix Hydrogels for Craniofacial Bone Tissue Regeneration.

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Project Summary/Abstract There is a clinical need for craniofacial bone augmentation in cases of trauma, tumor resection, congenital malformations, or bone resorption as a result of tooth extraction or periodontal disease. Currently, bone autograft, which is associated with increased risk of donor site morbidity and infection, and non-resorbable barrier membranes, which required additional procedures for removal, are the standard of treatment. Therefore, the objective of this research is to develop 3D printed scaffolds for craniofacial bone augmentation using a clinically relevant material, demineralized bone matrix, for guided bone regeneration. The fundamental hypothesis for this research project is that the endogenous biochemical cues for bone regeneration found within demineralized bone matrix combined with the ability to tune scaffold microarchitecture and crosslinking via 3D printing will result in improved bone augmentation. Two specific aims will be investigated to accomplish the goals of this project. In the first specific aim, we will fabricate 3D-printed scaffolds composed of demineralized bone matrix nanoparticles with varied pore sizes and UV crosslinking times. The mechanical properties and degradation kinetics of these scaffolds will then be characterized via compressive testing, bulk swelling, and mass loss studies. Additionally, the in vitro osteogenic potential of the demineralized bone matrix scaffolds will be evaluated using mesenchymal stem cells and measured by alkaline phosphatase expression, calcium content, and markers of osteogenic differentiation. The results of this specific aim will elucidate the role of pore size and UV crosslinking in determining the osteogenic potential of demineralized bone matrix scaffolds and determine which groups are appropriate for in vivo translation. In the second specific aim, we will investigate the in vivo osteoinductive and osteoconductive capacity of 3D-printed demineralized bone matrix scaffolds. The scaffolds will be implanted in a rat parietal bone augmentation model for 12 weeks and assessed via micro-CT and histology for newly formed bone volume, maximum bone height, and bone quality. Upon completion of the proposed work, we will have determined the in vitro and in vivo bone regeneration efficacy of an acellular, 3D-printed demineralized bone matrix scaffold and demonstrated tunability of scaffold mechanical properties and degradation. Additionally, the proposed work provide new insights into rational 3D- printed scaffold design and fabrication for craniofacial applications.