title: Three-Dimensional Printing of Bone Extracellular Matrix for Craniofacial Regeneration.
abstract: Tissue-engineered approaches to regenerate bone in the craniomaxillofacial region utilize biomaterial scaffolds to provide structural and biological cues to stem cells to stimulate osteogenic differentiation. Bioactive scaffolds are typically comprised of natural components but often lack the manufacturability of synthetic materials. To circumvent this trade-off, we 3D printed materials comprised of decellularized bone (DCB) matrix particles combined with polycaprolactone (PCL) to create novel hybrid DCB:PCL scaffolds for bone regeneration. Hybrid scaffolds were readily printable at compositions of up to 70% bone by mass and displayed robust mechanical properties. Assessments of surface features revealed both collagenous and mineral components of bone were present. Qualitative and quantitative assessments showed increased surface roughness relative to that of pure PCL scaffolds. These findings correlated with enhanced cell adhesion on hybrid surfaces relative to that on pure surfaces. Human adipose-derived stem cells (hASCs) cultured in DCB:PCL scaffolds without soluble osteogenic cues exhibited significant upregulation of osteogenic genes in hybrid scaffolds relative to pure PCL scaffolds. In the presence of soluble phosphate, hybrid scaffolds resulted in increased calcification. The hASC-seeded scaffolds were implanted into critical-sized murine calvarial defects and yielded greater bone regeneration in DCB:PCL scaffolds compared to that in PCL-only at 1 and 3 months post-transplantation. Taken together, these results demonstrate that 3D printed DCB:PCL scaffolds might be effective for stimulating bone regeneration.
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States.
authors.forename: Ben P
authors.initials: BP
authors.lastname: Hung
authors.affiliation: Fischell Department of Biomedical Engineering, University of Maryland, College Park, Maryland 21231, United States.
authors.forename: Bilal A
authors.initials: BA
authors.lastname: Naved
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States.
authors.forename: Ethan L
authors.initials: EL
authors.lastname: Nyberg
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States.
authors.forename: Miguel
authors.initials: M
authors.lastname: Dias
authors.affiliation: Department of Neurosurgery, The Johns Hopkins Hospital, Baltimore 21231, Maryland, United States.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Holmes
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Elisseeff
authors.affiliation: Department of Plastic Surgery, The Johns Hopkins Hospital, Baltimore 21231, Maryland, United States.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Dorafshar
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States; Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore 21231, Maryland, United States.
authors.forename: Warren L
authors.initials: WL
authors.lastname: Grayson
keywords: 3D-printing; biomaterials; bone regeneration; decellularized bone; tissue engineering