IP Library › Granted Patent US 12,246,113
Granted Patent B2
US 12,246,113 · App. 17/266,807 · Granted Mar 11, 2025

Fabrication of porous scaffolds using additive manufacturing with potential applications in bone tissue engineering

Inventors: Hernan Lara Padilla (Columbus, OH); David Dean (Columbus, OH); Ciro Rodriguez (Columbus, OH)
Assignee: Ohio State Innovation Foundation
A61L27/56A61L27/16B22F10/12B22F10/14B22F10/18B22F10/25B22F10/28B22F10/36B22F10/38B22F10/85B22F12/90B29C64/165B29C64/393B33Y10/00B33Y50/02B33Y80/00C12M23/44C12M29/10A61L2430/02
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,246,113
App. No.
17/266,807
Granted
Mar 11, 2025
Kind
B2
Abstract

The present disclosure describes additive manufacturing methods, in particular methods for optimizing the manufacture of objects by three-dimensional printing processes. Also provided are bioreactors as well as methods of using thereof.

Claims (24)

1. A method for optimizing a stereolithographic additive manufacturing process for the production of a three-dimensional object using a stereolithographic additive manufacturing device, the method comprising:

(a) actuating a build plate to separate a test layer from the build plate;

(b) measuring a separation force required to separate the test layer from the build plate with a force sensor during step (a);

(c) repeating steps (a) and (b) to form one or more additional layers having one or more additional cross-sectional areas until there is a failure of interlayer binding of any two of the layers upon activation of the build plate;

(d) calculating an interlayer green strength by dividing the separation force measured for a most recent additional layer manufactured during step (c) upon failure of interlayer binding by the additional cross-sectional area of the most recent additional layer; and

(e) calculating a probability of structural failure of the test layer by comparing the separation force of the test layer with the interlayer green force;

wherein if the separation force of the test layer is greater than the interlayer green force, then a resin composition is modified, a cross-sectional overlap between the test layer and one or more adjacent layers is increased, an incident energy generated by the stereolithographic additive manufacturing device during the stereolithographic additive manufacturing process is modified, or a combination thereof.

2. The method of claim 1 , wherein the stereolithographic additive manufacturing process comprises a Vat photopolymerization.

3. The method of claim 1 , wherein the stereolithographic additive manufacturing process comprises continuous digital light processing (cDLP).

4. The method of claim 1 , wherein the stereolithographic additive manufacturing device comprises a digital micromirror device (DMD), a transparent or translucent basement plate, and the build plate operatively coupled to the force sensor.

5. The method of claim 1 , wherein the resin composition comprises a liquid light-curable material and a photoinitiator.

6. The method of claim 5 , wherein the liquid light-curable material comprises a polymer.

7. The method of claim 6 , wherein the polymer comprises poly(propylene fumarate) (PPF).

8. The method of claim 6 , wherein the polymer has a molecular weight of 4,000 Daltons or less.

9. The method of claim 1 , wherein the resin composition comprises a first liquid light-curable material and a photoinitiator, and wherein modification of the resin composition comprises selecting a different liquid light-curable material.

10. The method of claim 9 , wherein the different liquid light-curable material exhibits different rheological properties than the first liquid light-curable material.

11. The method of claim 1 , wherein the resin composition comprises a liquid light-curable material, a photoinitiator, and a dye.

12. The method of claim 11 , wherein modification of the resin composition comprises altering a ratio of the dye to the photoinitiator.

13. The method of claim 11 , wherein the dye comprises 2-hydroxy-4-methoxybenzophenone.

14. The method of claim 5 , wherein the photoinitiator is selected from the group consisting of bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (BAPO), bis[2,6-difluoro-3-(1-hydroxypyrrol-1-yl)phenyl]titanocene, or a combination thereof.

15. The method of claim 1 , wherein the resin composition further comprises a solvent.

16. The method of claim 1 , wherein the resin composition further comprises a reactive diluent.

17. The method of claim 16 , wherein the reactive diluent is selected from the group consisting of N-vinyl pyrrolidone, diethyl fumarate (DEF), or a combination thereof.

18. The method of claim 1 , wherein modification of the incident energy generated by the stereolithographic additive manufacturing device during the stereolithographic additive manufacturing process is selected from the group consisting of varying a wavelength of incident light, varying an intensity of incident light, varying a duration of incident light, or a combination thereof.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jan 12, 2022
From: OHIO UNIVERSITY
To: THE GOVERNMENT OF THE UNITED STATES AS REPRESENTED BY THE SECRETARY OF THE ARMY
Reel/Frame 058717/0807 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 8, 2021
From: PADILLA, HERNAN LARA; DEAN, DAVID; RODRIGUEZ, CIRO
To: OHIO STATE INNOVATION FOUNDATION
Reel/Frame 055182/0078 →
Continuity (2)
Provisional Application 62715596 · Aug 7, 2018
Related Publication 20210316367A1 · Oct 14, 2021
References Cited (65)
US 5182056A · Spence et al. · 1993 [cited by applicant]
US 6048954A · Barlow et al. · 2000 [cited by applicant]
US 20090256284A1 · McGuire et al. · 2009 [cited by applicant]
US 20150314039A1 · Dean et al. · 2015 [cited by applicant]
US 20170057178A1 · FrantzDale · 2017 [cited by examiner]
US 20170297097A1 · Gibson et al. · 2017 [cited by applicant]
Communication pursuant to Article 94(3) EPC dated Jul. 18, 2023, for European Application No. 19846543.7. 7 pages. [cited by applicant]
Partial Supplementary European Search Report issued for Application No. 19846543.7, dated Feb. 24, 2022. [cited by applicant]
International Preliminary Report on Patentability issued for Application No. PCT/US2019/045588, dated Feb. 18, 2021. [cited by applicant]
Abhay, Sanan, and Stephen J. Haines. “Repairing Holes in the Head: A History of Cranioplasty.” Neurosurgery, Mar. 1997, 588-603. https://doi.org/10.1097/0006123-199703000-00033. [cited by applicant]
Banic, Andrej, and Ralph Hertel. 1993. “Double Vascularized Fibulas for Reconstruction of Large Tibial Defects.” Journal of Reconstructive Microsurgery 9 (06): 421-28. https://doi.org/10.1055/s-2007-1006751. [cited by applicant]
Basu, Bikramjit. 2017. “Natural Bone and Tooth: Structure and Properties.” In Biomaterials for Musculoskeletal Regeneration, 45-85. Indian Institute of Metals Series. Springer, Singapore. https://doi.org/10.1007/978-981… [cited by applicant]
Béchet, E., J.-C. Cuilliere, and F. Trochu. 2002. “Generation of a Finite Element MESH from Stereolithography (STL) Files.” Computer-Aided Design 34 (1): 1-17. https://doi.org/10.1016/S0010-4485(00)00146-9. [cited by applicant]
Van Bochove, Bas, Gerjon Hannink, Pieter Buma, and Dirk W. Grijpma. 2016. “Preparation of Designed Poly(Trimethylene Carbonate) Meniscus Implants by Stereolithography: Challenges in Stereolithography.” Macromolecular Bi… [cited by applicant]
Burr, David B., A. G. Robling, and C. H. Turner. 2002. “Effects of Biomechanical Stress on Bones in Animals.” Bone 30 (5): 781-86. [cited by applicant]
Choi, Jae-Won, Ryan Wicker, Seok-Hee Lee, Kyung-Hyun Choi, Chang-Sik Ha, and Ildoo Chung. 2009. “Fabrication of 3D Biocompatible/Biodegradable Micro-Scaffolds Using Dynamic Mask Projection Microstereolithography.” Journ… [cited by applicant]
Cignoni, Paolo, Marco Callieri, Massimiliano Corsini, Matteo Dellepiane, Fabio Ganovelli, and Guido Ranzuglia. 2008. MeshLab: An Open-Source Mesh Processing Tool. The Eurographics Association. http://dx.doi.org/10.2312/… [cited by applicant]
Dean, David, Jonathan Wallace, Ali Siblani, Martha O. Wang, Kyobum Kim, Antonios G. Mikos, and John P. Fisher. 2012. “Continuous Digital Light Processing (CDLP): Highly Accurate Additive Manufacturing of Tissue Engineer… [cited by applicant]
DeCoster, Thomas A., Rick J. Gehlert, Elizabeth A. Mikola, and Miguel A. Pirela-Cruz. 2004. “Management of Posttraumatic Segmental Bone Defects.” The Journal of the American Academy of Orthopaedic Surgeons 12 (1): 28-38. [cited by applicant]
Gardel, Leandro S., Luís A. Serra, Rui L. Reis, and Manuela E. Gomes. 2014. “Use of Perfusion Bioreactors and Large Animal Models for Long Bone Tissue Engineering.” Tissue Engineering. Part B, Reviews 20 (2): 126-46. ht… [cited by applicant]
Geuzaine, Christophe, and Jean-François Remacle. 2009. “Gmsh: A 3-D Finite Element Mesh Generator with Built-in Pre- and Post-Processing Facilities.” International Journal for Numerical Methods in Engineering 79 (11): 1… [cited by applicant]
Giannitelli, S. M., D. Accoto, M. Trombetta, and A. Rainer. 2014. “Current Trends in the Design of Scaffolds for Computer-Aided Tissue Engineering.” Acta Biomaterialia 10 (2): 580-94. https://doi.org/10.1016/j.actbio.20… [cited by applicant]
Giannitelli, S. M., P. Mozetic, M. Trombetta, and A. Rainer. 2015a. “Combined Additive Manufacturing Approaches in Tissue Engineering.” Acta Biomaterialia 24 (Sep.): 1-11. https://doi.org/10.1016/j.actbio.2015.06.032. [cited by applicant]
Giannoudis, Peter V., Haralambos Dinopoulos, and Eleftherios Tsiridis. 2005. “Bone Substitutes: An Update.” Injury 36 Suppl 3 (Nov.): S20-27. https://doi.org/10.1016/j.injury.2005.07.029. [cited by applicant]
Griffin, Kaitlyn S., Korbin M. Davis, Todd O. McKinley, Jeffrey O. Anglen, Tien-Min G. Chu, Joel D. Boerckel, and Melissa A. Kacena. 2015. “Evolution of Bone Grafting: Bone Grafts and Tissue Engineering Strategies for V… [cited by applicant]
Haj, A. J. El, and S. H. Cartmell. 2010. “Bioreactors for Bone Tissue Engineering.” Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 224 (12): 1523-32. https://doi.org/1… [cited by applicant]
Hollister, Scott J. 2005a. “Porous Scaffold Design for Tissue Engineering.” Nature Materials 4 (7): 518-24. https://doi.org/10.1038/nmat1421. [cited by applicant]
Holzapfel, Boris Michael, Johannes Christian Reichert, Jan-Thorsten Schantz, Uwe Gbureck, Lars Rackwitz, Ulrich Nöth, Franz Jakob, Maximilian Rudert, Jürgen Groll, and Dietmar Werner Hutmacher. 2013a. “How Smart Do Biom… [cited by applicant]
Huang, You-Min, and Cho-Pei Jiang. 2005. “On-Line Force Monitoring of Platform Ascending Rapid Prototyping System.” Journal of Materials Processing Technology 159 (2): 257-64. https://doi.org/10.1016/j.jmatprotec.2004.0… [cited by applicant]
Hutmacher, D. W. 2000. “Scaffolds in Tissue Engineering Bone and Cartilage.” Biomaterials 21 (24): 2529-43. [cited by applicant]
Ibrahim, A. 2018. “13—3D Bioprinting Bone.” In 3D Bioprinting for Reconstructive Surgery, edited by Daniel J. Thomas, Zita M. Jessop, and Iain S. Whitaker, 245-75. Woodhead Publishing. https://doi.org/10.1016/B978-0-08-… [cited by applicant]
“Introduction to Reliability Engineering.” 2011. In Practical Reliability Engineering, by Patrick D. T. O'Connor and Andre Kleyner, 1-18. Chichester, UK: John Wiley & Sons, Ltd. https://doi.org/10.1002/9781119961260.ch1. [cited by applicant]
Ivanovski, S., C. Vaquette, S. Gronthos, D. W. Hutmacher, and P. M. Bartold. 2014. “Multiphasic Scaffolds for Periodontal Tissue Engineering.” Journal of Dental Research 93 (12): 1212-21. https://doi.org/10.1177/0022034… [cited by applicant]
Jariwala, Shailly H., Gregory S. Lewis, Zachary J. Bushman, James H. Adair, and Henry J. Donahue. 2015. “3D Printing of Personalized Artificial Bone Scaffolds.” 3d Printing and Additive Manufacturing 2 (2): 56-64. https… [cited by applicant]
Karageorgiou, Vassilis, and David Kaplan. 2005. “Porosity of 3D Biomaterial Scaffolds and Osteogenesis.” Biomaterials 26 (27): 5474-91. https://doi.org/10.1016/j.biomaterials.2005.02.002. [cited by applicant]
Karande, Tejas S., Joo L. Ong, and C. Mauli Agrawal. 2004. “Diffusion in Musculoskeletal Tissue Engineering Scaffolds: Design Issues Related to Porosity, Permeability, Architecture, and Nutrient Mixing.” Annals of Biome… [cited by applicant]
Kinaci, Ahmet, Valentin Neuhaus, and David C. Ring. 2014. “Trends in Bone Graft Use in the United States.” Orthopedics 37 (9): e783-788. https://doi.org/10.3928/01477447-20140825-54. [cited by applicant]
Kovalenko, Jaroslav, Sylvain Verron, Maryna Garan, Jiří Šafka, and Michal Moučka. 2017. “Implementation of Non-Destructive Evaluation and Process Monitoring in DLP-Based Additive Manufacturing.” Open Engineering 7 (1): … [cited by applicant]
Langer, R., and J. P. Vacanti. 1993. “Tissue Engineering.” Science (New York, N.Y.) 260 (5110): 920-26. [cited by applicant]
Laurencin, Cato, Yusuf Khan, and Saadiq F. El-Amin. 2006. “Bone Graft Substitutes.” Expert Review of Medical Devices 3 (1): 49-57. https://doi.org/10.1586/17434440.3.1.49. [cited by applicant]
Lian, Qin, Fei Yang, Hua Xin, and Dichen Li. 2017. “Oxygen-Controlled Bottom-up Mask-Projection Stereolithography for Ceramic 3D Printing.” Ceramics International 43 (17): 14956-61. https://doi.org/10.1016/j.ceramint.20… [cited by applicant]
Melchels, Ferry P. W., Jan Feijen, and Dirk W. Grijpma. 2009. “A Poly(D,L-Lactide) Resin for the Preparation of Tissue Engineering Scaffolds by Stereolithography.” Biomaterials 30 (23-24): 3801-9. https://doi.org/10.101… [cited by applicant]
Meyer, Ulrich. 2009. “The History of Tissue Engineering and Regenerative Medicine in Perspective.” In Fundamentals of Tissue Engineering and Regenerative Medicine, 5-12. Springer, Berlin, Heidelberg. https://doi.org/10.… [cited by applicant]
Meyer, Ulrich, Hans Peter Wiesmann, Jörg Handschel, and Norbert R. Kübler. 2009. “Bone Tissue Engineering.” In Fundamentals of Tissue Engineering and Regenerative Medicine, 211-32. Springer, Berlin, Heidelberg. https://… [cited by applicant]
Mott, Eric J., Mallory Busso, Xinyi Luo, Courtney Dolder, Martha O. Wang, John P. Fisher, and David Dean. 2016. “Digital Micromirror Device (DMD)-Based 3D Printing of Poly(Propylene Fumarate) Scaffolds.” Materials Scien… [cited by applicant]
Nerem, Robert M., and Stacey C. Schutte. 2014. “Chapter 2—The Challenge of Imitating Nature.” In Principles of Tissue Engineering (Fourth Edition), 9-24. Boston: Academic Press. https://doi.org/10.1016/B978-0-12-398358-… [cited by applicant]
Ng, Vincent Y. 2012. “Risk of Disease Transmission with Bone Allograft.” Orthopedics 35 (8): 679-81. https://doi.org/10.3928/01477447-20120725-04. [cited by applicant]
Pan, Yayue, Haiyang He, Jie Xu, and Alan Feinerman. 2017. “Study of Separation Force in Constrained Surface Projection Stereolithography.” Rapid Prototyping Journal 23 (2): 353-61. https://doi.org/10.1108/RPJ-12-2015-01… [cited by applicant]
Pangborn, Christine A., and Kyriacos A. Athanasiou. 2005. “Growth Factors and Fibrochondrocytes in Scaffolds.” Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society 23 (5): 1184-90. h… [cited by applicant]
Rodriguez, Ciro A., Hernan Lara-Padilla, and David Dean. 2018. “Bioceramics for Musculoskeletal Regenerative Medicine: Materials and Manufacturing Process Compatibility for Synthetic Bone Grafts and Medical Devices.” In… [cited by applicant]
Rosser, J., and D. J. Thomas. 2018. “10—Bioreactor Processes for Maturation of 3D Bioprinted Tissue.” In 3D Bioprinting for Reconstructive Surgery, 191-215. Woodhead Publishing. https://doi.org/10.1016/B978-0-08-101103-… [cited by applicant]
Salgado, António J., Olga P. Coutinho, and Rui L. Reis. 2004. “Bone Tissue Engineering: State of the Art and Future Trends.” Macromolecular Bioscience 4 (8): 743-65. https://doi.org/10.1002/mabi.200400026. [cited by applicant]
Schneider, Caroline A., Wayne S. Rasband, and Kevin W. Eliceiri. 2012. “NIH Image to ImageJ: 25 Years of Image Analysis.” Nature Methods 9 (7): 671-75. [cited by applicant]
Sela, Jona J., and Itai A. Bab. 2012. “Healing of Bone Fracture: General Concepts.” In Principles of Bone Regeneration, 1-8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2059-0_1. [cited by applicant]
Sipos, Wolfgang, Ursula Föger-Samwald, and Peter Pietschmann. 2014. “Supporting Apparatus of Vertebrates: Skeleton and Bones.” In Comparative Medicine, 35-44. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1559-6_… [cited by applicant]
Sladkova, Martina, and Giuseppe Maria de Peppo. 2014. “Bioreactor Systems for Human Bone Tissue Engineering.” Processes 2 (2): 494-525. https://doi.org/10.3390/pr2020494. [cited by applicant]
Sun, C., N. Fang, D. M. Wu, and X. Zhang. 2005. “Projection Micro-Stereolithography Using Digital Micro-Mirror Dynamic Mask.” Sensors and Actuators A: Physical 121 (1): 113-20. https://doi.org/10.1016/j.sna.2004.12.011. [cited by applicant]
Taubin, G. 1995. “Curve and Surface Smoothing without Shrinkage.” In Proceedings of IEEE International Conference on Computer Vision, 852-57. https://doi.org/10.1109/ICCV.1995.466848. [cited by applicant]
Walker, Jason M., Emily Bodamer, Alex Kleinfehn, Yuanyuan Luo, Matthew Becker, and David Dean. 2017. “Design and Mechanical Characterization of Solid and Highly Porous 3D Printed Poly(Propylene Fumarate) Scaffolds.” Pro… [cited by applicant]
Wendt, D., S. A. Riboldi, M. Cioffi, and I. Martin. 2009. “Bioreactors in Tissue Engineering: Scientific Challenges and Clinical Perspectives.” Advances in Biochemical Engineering/Biotechnology 112: 1-27. https://doi.or… [cited by applicant]
Wu, Xiangquan, Qin Lian, Dichen Li, and Zhongmin Jin. 2017. “Tilting Separation Analysis of Bottom-up Mask Projection Stereolithography Based on Cohesive Zone Model.” Journal of Materials Processing Technology 243 (May)… [cited by applicant]
Yeatts, Andrew B., and John P. Fisher. 2011. “Bone Tissue Engineering Bioreactors: Dynamic Culture and the Influence of Shear Stress.” Bone 48 (2): 171-81. https://doi.org/10.1016/j.bone.2010.09.138. [cited by applicant]
Zhou, Chi, Yong Chen, Zhigang Yang, and Behrokh Khoshnevis. 2013. “Digital Material Fabrication Using Mask-image-projection-based Stereolithography.” Rapid Prototyping Journal 19 (3): 153-65. https://doi.org/10.1108/135… [cited by applicant]
International Search Report and Written Opinion issued by the International Searching Authority (ISA/US) in PCT Application No. PCT/US2019/045588 on Nov. 21, 2019. 12 pages. [cited by applicant]
Extended European Search report issued for Application No. 19846543.7, dated May 30, 2022. [cited by applicant]