title: Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.
abstract: Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.
authors.affiliation: Department of Mechanical Engineering, KU Leuven, Celestijnenlaan 300 C, PB 2419, B-3001 Leuven, Belgium. Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, O&N 1, Herestraat 49, PB 813, B-3000 Leuven, Belgium.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Carlier
authors.forename: Gözde Akdeniz
authors.initials: GA
authors.lastname: Skvortsov
authors.forename: Forough
authors.initials: F
authors.lastname: Hafezi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ferraris
authors.forename: Jennifer
authors.initials: J
authors.lastname: Patterson
authors.forename: Bahattin
authors.initials: B
authors.lastname: Koç
authors.forename: Hans
authors.initials: H
authors.lastname: Van Oosterwyck
mesh_terms: D000818:Animals; D062028:Bioprinting; D001861:Bone Regeneration; D001842:Bone and Bones / Q000166:cytology* / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D019295:Computational Biology; D005347:Fibroblasts / Q000166:cytology*; D020100:Hydrogels / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020100:Hydrogels