Transplantation of Bioprinted Tissues and Organs nges and Future Perspectives Technical and Clinical Challe

Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, costeffective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

[1]  Ibrahim T. Ozbolat,et al.  Characterization of printable cellular micro-fluidic channels for tissue engineering , 2013, Biofabrication.

[2]  Anthony Atala,et al.  Smart biomaterials design for tissue engineering and regenerative medicine. , 2007, Biomaterials.

[3]  Yimin Zhao,et al.  Clinical transplantation of a tissue-engineered airway , 2009, The Lancet.

[4]  James J. Yoo,et al.  Tissue-engineered autologous bladders for patients needing cystoplasty , 2006, The Lancet.

[5]  J. Barkin,et al.  Stomach , 2015, The American Journal of Gastroenterology.

[6]  James J. Yoo,et al.  A 3D bioprinting system to produce human-scale tissue constructs with structural integrity , 2016, Nature Biotechnology.

[7]  Kartik V. Bulusu,et al.  A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair , 2016, Nanotechnology.

[8]  R. Bracci,et al.  Bioresorbable Airway Splint Created with a Three-Dimensional Printer , 2013 .

[9]  A. Israni,et al.  OPTN/SRTR 2013 Annual Data Report: Economics , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  Philip Tack,et al.  3D-printing techniques in a medical setting: a systematic literature review , 2016, BioMedical Engineering OnLine.

[11]  J. J. Sáez,et al.  Transplant Tolerance: New Insights and Strategies for Long-Term Allograft Acceptance , 2013, Clinical & developmental immunology.

[12]  A. Khojasteh,et al.  Polymeric vs hydroxyapatite-based scaffolds on dental pulp stem cell proliferation and differentiation. , 2015, World journal of stem cells.

[13]  Antoni Bayes-Genis,et al.  Neoinnervation and neovascularization of acellular pericardial-derived scaffolds in myocardial infarcts , 2015, Stem Cell Research & Therapy.

[14]  Ibrahim T. Ozbolat,et al.  Bioprinting Technology: A Current State-of-the-Art Review , 2014 .

[15]  A. Dua,et al.  Changing paradigms in organ preservation and resuscitation , 2015, Current opinion in organ transplantation.

[16]  J. Simon,et al.  Immune responses to implants - a review of the implications for the design of immunomodulatory biomaterials. , 2011, Biomaterials.

[17]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[18]  David T Corr,et al.  Gelatin-based laser direct-write technique for the precise spatial patterning of cells. , 2011, Tissue engineering. Part C, Methods.

[19]  R. Shivdasani,et al.  Stomach development, stem cells and disease , 2016, Development.

[20]  Michael T. Longaker,et al.  Organogenesis Particularly Relevant to Fetal Surgery , 2003, World Journal of Surgery.

[21]  T. Evans,et al.  Orchestrating liver development , 2015, Development.

[22]  Xuan Zhou,et al.  3D Bioprinting a Cell-Laden Bone Matrix for Breast Cancer Metastasis Study. , 2016, ACS applied materials & interfaces.

[23]  L. Niklason,et al.  Scaffold-free vascular tissue engineering using bioprinting. , 2009, Biomaterials.

[24]  Ibrahim T. Ozbolat,et al.  Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink , 2016, Scientific Reports.

[25]  Mark W. Tibbitt,et al.  Hydrogels as extracellular matrix mimics for 3D cell culture. , 2009, Biotechnology and bioengineering.

[26]  Seung-Schik Yoo,et al.  Generation of Multi-scale Vascular Network System Within 3D Hydrogel Using 3D Bio-printing Technology , 2014, Cellular and molecular bioengineering.

[27]  Gabor Forgacs,et al.  Biofabrication and testing of a fully cellular nerve graft , 2013, Biofabrication.

[28]  Chuck Zhang,et al.  Bioprinting: an assessment based on manufacturing readiness levels. , 2017, Critical reviews in biotechnology.

[29]  Byung-Soo Kim,et al.  Nanothin Coculture Membranes with Tunable Pore Architecture and Thermoresponsive Functionality for Transfer-Printable Stem Cell-Derived Cardiac Sheets. , 2015, ACS nano.

[30]  Ibrahim T. Ozbolat,et al.  Current advances and future perspectives in extrusion-based bioprinting. , 2016, Biomaterials.

[31]  Deok‐Ho Kim,et al.  Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink , 2014, Nature Communications.

[32]  H. Mizuno,et al.  REGENERATIVE MEDICINE Concise Review: Adipose-Derived Stem Cells as a Novel Tool for Future Regenerative Medicine , 2012 .

[33]  H. Lorenz,et al.  Multilineage cells from human adipose tissue: implications for cell-based therapies. , 2001, Tissue engineering.

[34]  Ibrahim T. Ozbolat,et al.  A Hybrid Bioprinting Approach for Scale-Up Tissue Fabrication , 2014 .

[35]  E. Dzierzak,et al.  Hypoxia and HIFs in regulating the development of the hematopoietic system. , 2013, Blood cells, molecules & diseases.

[36]  C. L. Ventola Medical Applications for 3D Printing: Current and Projected Uses. , 2014, P & T : a peer-reviewed journal for formulary management.

[37]  A. Mccarthy Development , 1996, Current Opinion in Neurobiology.

[38]  Ali Khademhosseini,et al.  Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design , 2016, Advanced healthcare materials.

[39]  Alan Faulkner-Jones,et al.  Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D , 2015, Biofabrication.

[40]  Kirsten Borchers,et al.  Methacrylated gelatin and mature adipocytes are promising components for adipose tissue engineering , 2016, Journal of biomaterials applications.

[41]  H. Geiger,et al.  Adipose-Derived Mesenchymal Stromal/Stem Cells: Tissue Localization, Characterization, and Heterogeneity , 2012, Stem cells international.

[42]  Z. Alfonso,et al.  Adipose-derived stem cells. , 2008, Methods in molecular biology.

[43]  N. Jasiak,et al.  Immunosuppression in Solid-Organ Transplantation: Essentials and Practical Tips , 2016, Critical care nursing quarterly.

[44]  L. Martínez-Dolz,et al.  Sympathetic reinnervation 1 year after heart transplantation, assessed using iodine-123 metaiodobenzylguanidine imaging. , 2011, Transplantation proceedings.

[45]  J. T. Harbaugh Do You Own Your 3D Bioprinted Body? , 2015, American Journal of Law & Medicine.

[46]  E. Benrashid,et al.  Tissue engineered vascular grafts: Origins, development, and current strategies for clinical application. , 2016, Methods.

[47]  Christopher J. Duffy,et al.  The role of macropores and multi-resolution soil survey datasets for distributed surface–subsurface flow modeling , 2014 .

[48]  E. Rodriguez,et al.  The Face Transplantation Update: 2016 , 2016, Plastic and reconstructive surgery.

[49]  B. Brown,et al.  Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. , 2012, Biomaterials.

[50]  D. Orgill,et al.  Tissue-engineered skin substitutes. , 1999, Expert opinion on investigational drugs.

[51]  Gordon G Wallace,et al.  Functional 3D Neural Mini‐Tissues from Printed Gel‐Based Bioink and Human Neural Stem Cells , 2016, Advanced healthcare materials.

[52]  Vladimir Mironov,et al.  Tissue spheroid fusion‐based in vitro screening assays for analysis of tissue maturation , 2010, Journal of tissue engineering and regenerative medicine.

[53]  C. V. van Blitterswijk,et al.  Spheroid culture as a tool for creating 3D complex tissues. , 2013, Trends in biotechnology.

[54]  Pankaj Karande,et al.  Design and fabrication of human skin by three-dimensional bioprinting. , 2014, Tissue engineering. Part C, Methods.

[55]  Ibrahim T. Ozbolat,et al.  Direct Bioprinting of Vessel-Like Tubular Microfluidic Channels , 2013 .

[56]  P. Gaspar,et al.  Probing the diversity of serotonin neurons , 2012, Philosophical Transactions of the Royal Society B: Biological Sciences.

[57]  R. Cancedda,et al.  Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds. , 2009, Carcinogenesis.

[58]  C. Simmons,et al.  Interaction of a block-co-polymeric biomaterial with immunoglobulin G modulates human monocytes towards a non-inflammatory phenotype. , 2015, Acta biomaterialia.

[59]  C. Simmons,et al.  Immunomodulatory polymeric scaffold enhances extracellular matrix production in cell co-cultures under dynamic mechanical stimulation. , 2015, Acta biomaterialia.

[60]  Lei Zhang,et al.  A Single B-Repeat of Staphylococcus epidermidis Accumulation-Associated Protein Induces Protective Immune Responses in an Experimental Biomaterial-Associated Infection Mouse Model , 2014, Clinical and Vaccine Immunology.

[61]  T. Okano,et al.  Controlling shape and position of vascular formation in engineered tissues by arbitrary assembly of endothelial cells , 2015, Biofabrication.

[62]  D. Mackey,et al.  Participant understanding and recall of informed consent for induced pluripotent stem cell biobanking , 2016, Cell and Tissue Banking.

[63]  Tingfei Xi,et al.  Regulation challenge of tissue engineering and regenerative medicine in China , 2013, Burns & Trauma.

[64]  M. Lanzettà,et al.  Human hand allograft: report on first 6 months , 1999, The Lancet.

[65]  Ibrahim T. Ozbolat,et al.  Bioprinting scale-up tissue and organ constructs for transplantation. , 2015, Trends in biotechnology.

[66]  D. Wilson A Troubled Past? Reassessing Ethics in the History of Tissue Culture , 2015, Health Care Analysis.

[67]  María Vallet-Regí,et al.  In-vivo behavior of Si-hydroxyapatite/polycaprolactone/DMB scaffolds fabricated by 3D printing. , 2013, Journal of biomedical materials research. Part A.

[68]  Manolis Kellis,et al.  Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells , 2014, Science.