Research

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, biomechanics. While we are currently working with human induced pluripotent stem cells (hiPSC) derived cardiomyocytes, we are expanding to work for thick vascularized tissue creation and mass production. As a surgical lab, we also implant these patches into animals to explore the potential of future clinical application. We are also working on genetic engineering and genome editing.

• Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. Ong CS, Fukunishi T, Zhang H, Huang CY, Nashed A, Blazeski A, DiSilvestre D, Vricella L, Conte J, Tung L, Tomaselli GF, Hibino N.  Sci Rep. 2017 Jul 4;7(1):4566. doi: 10.1038/s41598-017-05018-4. PMID: 28676704
• Mechanical stimulation enhances development of scaffold-free, 3D-printed, engineered heart tissue grafts.
  Lui C, Chin AF, Park S, Yeung E, Kwon C, Tomaselli G, Chen Y, Hibino N.J Tissue Eng Regen Med. 2021 Mar 21. doi: 10.1002/term.3188. Online ahead of print. PMID: 33749089
• Early Vascular Cells Improve Microvascularization Within 3D Cardiac Spheroids.
  Pitaktong I, Lui C, Lowenthal J, Mattson G, Jung WH, Bai Y, Yeung E, Ong CS, Chen Y, Gerecht S, Hibino N.Tissue Eng Part C Methods. 2020 Feb;26(2):80-90.
• Cardiac regeneration using human-induced pluripotent stem cell-derived biomaterial-free 3D-bioprinted cardiac patch in vivo.
  Yeung E, Fukunishi T, Bai Y, Bedja D, Pitaktong I, Mattson G, Jeyaram A, Lui C, Ong CS, Inoue T, Matsushita H, Abdollahi S, Jay SM, Hibino N.J Tissue Eng Regen Med. 2019 Nov;13(11):2031-2039. 
• 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

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. 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, Johns Hopkins Mechanical Engineering, Dr. John Fisher, University of Maryland, Nanofibersolutions, Secant Inc.).

• In vivo implantation of 3-dimensional printed customized branched tissue engineered vascular graft in a porcine model. Yeung E, Inoue T, Matsushita H, Opfermann J, Mass P, Aslan S, Johnson J, Nelson K, Kim B, Olivieri L, Krieger A, Hibino N.J Thorac Cardiovasc Surg. 2020 May;159(5):1971-1981.e1. 
• Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model. Fukunishi T, Best CA, Sugiura T, Opfermann J, Ong CS, Shinoka T, Breuer CK, Krieger A, Johnson J, Hibino N. J Thorac Cardiovasc Surg. 2017 Apr;153(4):924-932. doi: 10.1016/j.jtcvs.2016.10.066. Epub 2016 Nov 14. PMID: 27938900
• Role of surgeon intuition and computer-aided design in Fontan optimization: A computational fluid dynamics simulation study. Loke YH, Kim B, Mass P, Opfermann JD, Hibino N, Krieger A, Olivieri L.J Thorac Cardiovasc Surg. 2020 Jul;160(1):203-212.e2. 
• Virtual surgical planning, flow simulation, and 3-dimensional electrospinning of patient-specific grafts to optimize Fontan hemodynamics. 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.J Thorac Cardiovasc Surg. 2018 Apr;155(4):1734-1742.

• 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
• 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

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. Kunal Parikh 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