Award Abstract # 1600118
Bioprinting of Bone Tissue into Defect Sites on Animal Models in Surgery Settings

NSF Org: CMMI
Division of Civil, Mechanical, and Manufacturing Innovation
Recipient: THE PENNSYLVANIA STATE UNIVERSITY
Initial Amendment Date: November 30, 2015
Latest Amendment Date: January 13, 2016
Award Number: 1600118
Award Instrument: Standard Grant
Program Manager: Steve Schmid
CMMI
 Division of Civil, Mechanical, and Manufacturing Innovation
ENG
 Directorate for Engineering
Start Date: August 17, 2015
End Date: December 31, 2018 (Estimated)
Total Intended Award Amount: $300,947.00
Total Awarded Amount to Date: $310,947.00
Funds Obligated to Date: FY 2015 = $300,947.00
FY 2016 = $10,000.00
History of Investigator:
  • Ibrahim Ozbolat (Principal Investigator)
Recipient Sponsored Research Office: Pennsylvania State Univ University Park
201 OLD MAIN
UNIVERSITY PARK
PA  US  16802-1503
(814)865-1372
Sponsor Congressional District: 15
Primary Place of Performance: Pennsylvania State Univ University Park
101 Hammond Building
University Park
PA  US  16802-1400
Primary Place of Performance
Congressional District:
15
Unique Entity Identifier (UEI): NPM2J7MSCF61
Parent UEI:
NSF Program(s): Manufacturing Machines & Equip
Primary Program Source: 01001516DB NSF RESEARCH & RELATED ACTIVIT
01001617DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 082E, 083E, 116E, 9146, 9150, 9178, 9231, 9251, MANU
Program Element Code(s): 146800
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

The goal of this project is to establish a new frontier in bioprinting science and technology. This will be accomplished by studying the bioprinting of bone tissue directly into a defect site on an animal model. The research in this study will have a direct impact on the first-time bioprinting of living cells and nucleic acid loaded in polymers in surgery settings for bone tissue fabrication, which will benefit society by working toward the establishment of an alternative solution for skull defects. Skull defects are devastating and affect millions of people each year; about 7%, or 227,500, of the children born each year in the United States are affected by birth defects in the skull. Bioprinting in surgery settings will eventually be applied to other organs and will considerably improve quality of life for the affected people. Broader-impact activities will include training, education, and participation of underrepresented populations in summer camps and workshops, as well as the integration of next-generation bioprinting science into both graduate and undergraduate education.

The research objectives of this project are three-fold: 1) to understand bioprinting behavior of a composite bioink, 2) to determine the effects of bioprinting and the bioink parameters on the release profile and the transfection efficiency of plasmid, and 3) to understand bioprintability of porous tissue constructs in defects and establish the relationship between the manufacturing conditions of tissue constructs and bone tissue formation. Accomplishing these objectives will allow the exploration of advanced bioprinting technologies in operating rooms. In this project, the following tasks will be performed. First, a novel composite bioink (reinforced with collagen, stem cells, a thermo-sensitive gel, and plasmid) will be processed and characterized to research its bioprinting behavior. Then, bioprinting of plasmid will be studied to understand the role of bioprinting and the bioink parameters on sequential release and transfection efficiency of plasmid. Next, in situ multi-arm bioprinting will be studied to investigate manufacturability of multiple tissue constructs in critical-size cranial defects in rat models. Finally, the regenerated bone tissue, bioprinted under various manufacturing conditions, will be characterized and quantified using tissue histology and micro-computed tomography.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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(Showing: 1 - 10 of 19)
Anh-Vu Do, Adil Akkouch, Brian Green, Ibrahim Ozbolat, Amer Debabneh, Sean Geary, Aliasger K Salem "Controlled and Sequential Delivery of Fluorophores from 3D Printed Alginate-PLGA Tubes" Annals of Biomedical Engineering , v.45 , 2017 , p.297 https://doi.org/10.1007/s10439-016-1648-9
Ashley N. Leberfinger, Dino J. Ravnic, Aman Dhawan, Ibrahim T. Ozbolat "Concise Review: Bioprinting of Stem Cells for Transplantable Tissue Fabrication" Stem Cells Translational Medicine , v.6 , 2017 , p.1940 https://doi.org/10.1002/sctm.17-0148
Dino Ravnic, Ashley N Leberfinger, Srinivas Koduru, Monika Hospodiuk, Kazim K Moncal, Pallab Datta, Madhuri Dey, Elias Rizk, Ibrahim T Ozbolat "Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives" Annals of Surgery , v.226 , 2017 , p.48 doi: 10.1097/SLA.0000000000002141
Hemanth Gudapati, Madhuri Dey, Ibrahim Ozbolat "A Comprehensive Review on Droplet-based Bioprinting: Past, Present, Future" Biomaterials , v.102 , 2016 , p.20
Ibrahim Ozbolat and Hemanth Gudapati "A Review on Design for Bioprinting" Bioprinting , v.3-4 , 2016 , p.1
Ibrahim Ozbolat and Monika Hospodiuk "Current Advances and Future Directions in Extrusion-based Bioprinting" Biomaterials , v.76 , 2016 , p.321
Ibrahim Ozbolat, Weijie Peng, Veli Ozbolat "Application Areas of 3D Bioprinting" Drug Discovery Today , v.21 , 2016 , p.1257
Ibrahim T. Ozbolat, Kazim Moncal, HemanthGudapati "Evaluation of Bioprinter Technologies" Additive Manufacturing , v.13 , 2017 , p.179
Kazim K Moncal, Dong N Heo, Kevin P Godzik, Donna M Sosnoski, Oliver D Mrowczynski, Elias Rizk, Veli Ozbolat, Scott M Tucker, Ethan M Gerhard, Madhuri Dey, Gregory S Lewis, Jian Yang, Ibrahim T Ozbolat "3D printing of poly(?-caprolactone)/poly(D,L-lactide-co-glycolide)/hydroxyapatite composite constructs for bone tissue engineering" Journal of Materials Research , 2018 , p.1 DOI: 10.1557/jmr.2018.111
Monika Hospodiuk, Madhuri Dey, Donna Sosnoski, Ibrahim Ozbolat "The Bioink: A Comprehesive Review on Bioprintable Materials" Biotechnology Advances , v.35 , 2017 , p.217
Ozbolat, I.T. "Bioprinting Scale-up Tissue and Organ Constructs for Transplantation" Trends in Biotechnology , v.33 , 2015 , p.395 10.1016/j.tibtech.2015.04.005
(Showing: 1 - 10 of 19)

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

With this project, three-dimensional (3D) bioprinting of cells, proteins and genes in surgical settings has been demonstrated for cranial tissue repair, which enabled the successful regeneration of bone tissue. A new bioink formulation has been introduced and the rheological, biological and mechanical properties of that bioink were tuned to facilitate its extrusion into critical-size rat calvarial defects in aseptic conditions. It has been demonstrated that the addition of osteogenic particles, including plasmid deoxyribonucleic acid (DNA), micro ribonucleic acid (miRNA), bone morphogenetic protein-2 (BMP-2), or hydroxyapatite nano-particles, at increasing concentrations enhanced bone tissue regeneration in six weeks post implantation. Moreover, 3D Laser scanning has been integrated into bioprinting process planning in order to generate toolpath for in situ bioprinting into calvarial defects. In addition, bioprinting of composite tissues, including cranium and bi-layered skin tissue, has been demonstrated in a stratified arrangement on rats in surgical settings for the first time in the literature. 

 

During the project, three PhD students and three REU students have been trained on various aspects of 3D bioprinting such as synthesis and preparation of bioink materials, extrusion- and droplet-based bioprinting process development, 3D cell culture, animal handling and maintenance, and tissue characterization techniques. One of the PhD students already graduated and the other two have passed their comprehensive exams and are in the last year of their PhD studies. The PI has delivered more than 40 invited talks or seminars and the key results have been shared with the public and tissue engineering and bioprinting communities. In addition, one of the PhD students in the PI's laboratory has delivered more than 10 oral and poster presentations at local, national and international conferences.

 


Last Modified: 03/08/2019
Modified by: Ibrahim T Ozbolat

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