The main subjects of research in the Hibino lab are “Tissue Engineering X 3D Printing”, for application in cardiovascular surgery and medicine. As our research spans many fields, we collaborate extensively with different labs (in brackets below), providing a unique research environment.
Scaffold-free 3D cardiac tissue creation using 3D bioprinting
One of the main focus of the Hibino lab is to 3D bioprint cardiac patches without biomaterials, and characterize them using a variety of techniques, such as histology, immunohistochemistry, electrophysiology (Dr Leslie Tung, Biomedical Engineering, Johns Hopkins), biomechanics (Dr Yun Chen, Mechanical Engineering, Johns Hopkins). While we are currently working with human induced pluripotent stem cells (hiPSC) derived cardiomyocytes (Dr Gordon Tomaselli, Cardiology, Johns Hopkins), we are expanding to work with cardiac progenitor cells (Dr Chulan Kwon, Cardiology, Johns Hopkins), early vascular cells (Dr Sharon Gerecht, Johns Hopkins Institute for NanoBioTechnology), and adipose derived stem cells (Dr. Warren Grayson, Biomedical Engineering, Johns Hopkins). We also work on improving the maturity of these patches and strengthening their mechanical properties. As a surgical lab, we also implant these patches into animals. We are also working on genetic engineering and genome editing using CRISPR technologies (Dr Gordon Tomaselli, Cardiology, Johns Hopkins).
- Ong CS, Yesantharao P, Huang CY, Mattson G, Boktor J, Fukunishi T, Zhang H, Hibino N. 3D bioprinting using stem cells.Pediatr Res. 2017 Oct 6. doi: 10.1038/pr.2017.252. [Epub ahead of print] Review. PMID: 28985202
- Ong CS, Fukunishi T, Nashed A, Blazeski A, Zhang H, Hardy S, DiSilvestre D, Vricella L, Conte J, Tung L, Tomaselli G, Hibino N.Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting. J Vis Exp. 2017 Jul 2;(125). doi: 10.3791/55438. PMID: 28715377
- Ong CS, Fukunishi T, Zhang H, Huang CY, Nashed A, Blazeski A, DiSilvestre D, Vricella L, Conte J, Tung L, Tomaselli GF, Hibino N. Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. Sci Rep. 2017 Jul 4;7(1):4566. doi: 10.1038/s41598-017-05018-4. PMID: 28676704
- Moldovan NI, Hibino N, Nakayama K. Principles of the Kenzan Method for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting. Tissue Eng Part B Rev. 2017 Jan 3. doi: 10.1089/ten.TEB.2016.0322. [Epub ahead of print] PMID: 27917703
Tissue Engineered Vascular Grafts using 3D printing technology
Another focus of the Hibino lab is tissue-engineered vascular graft (TEVG) research. TEVGs offer the potential to overcome thrombogenicity, immune responses causing functional deterioration, and lack of growth potential by providing a biodegradable scaffold on which a patient’s own cells can proliferate and provide physiologic functionality. We investigate the conditions necessary to create the ideal TEVG, using a combination of cutting edge fabrication tools and polymers/biomaterials, as well as the mechanism of neotissue formation. Recently, by combining axial imaging technology, computer aided design, computational flow dynamics and artificial intelligence, with advanced 3D printing and biomaterials, we have created preoperatively designed, patient-specific TEVGs, that have the potential to improve surgical outcomes. These projects are multi-institutional collaboration (Dr. Dan Berkowitz/Lakshmi Santhanam, Anesthesiology, Johns Hopkins, Dr Sharon Gerecht and Dr. Hai- Quan Mao, Johns Hopkins Institute for NanoBioTechnology, Dr. Laura Olivieri, Children’s National Health System, Washington DC, Dr. Axel Krieger, Dr. John Fisher, University of Maryland, Nanofibersolutions, Secant Inc.).
- Siallagan D, Loke YH, Olivieri L, Opfermann J, Ong CS, de Zélicourt D, Petrou A, Daners MS, Kurtcuoglu V, Meboldt M, Nelson K, Vricella L, Johnson J, Hibino N, Krieger A. Virtual surgical planning, flow simulation and 3D electro-spinning of patient-specific grafts to optimize Fontan hemodynamics. JTCVS (Accepted).
- Liu RH, Ong CS, Fukunishi T, Ong K, Hibino N. Review of Vascular Graft Studies in Large Animal Models.Tissue Eng Part B Rev. 2017 Oct 5. doi: 10.1089/ten.TEB.2017.0350. [Epub ahead of print]PMID:2897826
- Ong CS, Fukunishi T, Liu RH, Nelson K, Zhang H, Wieczorek E, Palmieri M, Ueyama Y, Ferris E, Geist GE, Youngblood B, Johnson J, Hibino N. Bilateral Arteriovenous Shunts as a Method for Evaluating Tissue-Engineered Vascular Grafts in Large Animal Models. Tissue Eng Part C Methods. 2017 Sep 28. doi: 10.1089/ten.TEC.2017.0217. [Epub ahead of print] PMID: 28741438
- Fukunishi T, Best CA, Ong CS, Groehl T, Reinhardt J, Yi T, Miyachi H, Zhang H, Shinoka T, Breuer CK, Johnson J, Hibino N. Role of Bone Marrow Mononuclear Cell Seeding for Nanofiber Vascular Grafts. Tissue Eng Part A. 2017 May 9. doi: 10.1089/ten.TEA.2017.0044. [Epub ahead of print] PMID: 28486019
- Ong CS, Zhou X, Huang CY, Fukunishi T, Zhang H, Hibino N. Tissue engineered vascular grafts current state of the field. Expert Rev Med Devices. 2017 May;14(5):383-392. doi: 10.1080/17434440.2017.1324293. Epub 2017 May 9. PMID: 28447487
- Fukunishi T, Best CA, Sugiura T, Opfermann J, Ong CS, Shinoka T, Breuer CK, Krieger A, Johnson J, Hibino N. Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model. J Thorac Cardiovasc Surg. 2017 Apr;153(4):924-932. doi: 10.1016/j.jtcvs.2016.10.066. Epub 2016 Nov 14. PMID: 27938900
- Fukunishi T, Best CA, Sugiura T, Shoji T, Yi T, Udelsman B, Ohst D, Ong CS, Zhang H, Shinoka T, Breuer CK, Johnson J, Hibino N. Tissue-Engineered Small Diameter Arterial Vascular Grafts from Cell-Free Nanofiber PCL Chitosan Scaffolds in a Sheep Model. PLoS One. 2016 Jul 28;11(7):e0158555. doi: 10.1371/journal.pone.0158555. eCollection 2016. PMID: 27467821
Drug releasing surgical suture / TEVG
- We are trying to create a biodegradable drug-releasing suture and graft that will help to improve the quality and potency of sutures / grafts that are currently used in the clinical setting (Dr. Justin Hanes, Dr. Laura Ensign, Dr. Jung Soo Suk, Center for Nanomedicine, Johns Hopkins). By doing so, we can reduce stenosis, and induce native tissue regeneration with the newly developed technology.
Development of other methods to improve cardiac function and create 3D cardiac tissues