Advances and Future Perspectives in 4D Bioprinting

Three‐dimensionally printed constructs are static and do not recapitulate the dynamic nature of tissues. Four‐dimensional (4D) bioprinting has emerged to include conformational changes in printed structures in a predetermined fashion using stimuli‐responsive biomaterials and/or cells. The ability to make such dynamic constructs would enable an individual to fabricate tissue structures that can undergo morphological changes. Furthermore, other fields (bioactuation, biorobotics, and biosensing) will benefit from developments in 4D bioprinting. Here, the authors discuss stimuli‐responsive biomaterials as potential bioinks for 4D bioprinting. Natural cell forces can also be incorporated into 4D bioprinted structures. The authors introduce mathematical modeling to predict the transition and final state of 4D printed constructs. Different potential applications of 4D bioprinting are also described. Finally, the authors highlight future perspectives for this emerging technology in biomedicine.

[1]  Dandan Zhang,et al.  Design and preparation of matrine surface-imprinted material and studies on its molecule recognition selectivity , 2016, Journal of biomaterials science. Polymer edition.

[2]  Ali Khademhosseini,et al.  A Bioactive Carbon Nanotube‐Based Ink for Printing 2D and 3D Flexible Electronics , 2016, Advanced materials.

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

[4]  Jianping Fu,et al.  Fluorescent porous carbon nanocapsules for two-photon imaging, NIR/pH dual-responsive drug carrier, and photothermal therapy. , 2015, Biomaterials.

[5]  Yanzhong Zhang,et al.  Regulating drug release from pH- and temperature-responsive electrospun CTS-g-PNIPAAm/poly(ethylene oxide) hydrogel nanofibers , 2014, Biomedical materials.

[6]  Jeong-Woo Choi,et al.  Phototactic guidance of a tissue-engineered soft-robotic ray , 2016, Science.

[7]  Ali Khademhosseini,et al.  Three‐dimensional co‐culture of C2C12/PC12 cells improves skeletal muscle tissue formation and function , 2017, Journal of tissue engineering and regenerative medicine.

[8]  Ramalingam Murugan,et al.  Carbon Nanotubes and Graphene-Based Nanomaterials for Stem Cell Differentiation and Tissue Regeneration , 2016 .

[9]  Ben L. Feringa,et al.  Chiroptical Molecular Switches. , 2000, Chemical reviews.

[10]  Ali Khademhosseini,et al.  Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs , 2019, Materials today. Bio.

[11]  Ali Khademhosseini,et al.  Development of hydrogels for regenerative engineering , 2017, Biotechnology journal.

[12]  Kishor Sarkar,et al.  pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin delivery. , 2014, Carbohydrate polymers.

[13]  Hua Wei,et al.  Thermo-sensitive polymeric micelles based on poly(N-isopropylacrylamide) as drug carriers , 2009 .

[14]  A. Kasko,et al.  Photodegradable macromers and hydrogels for live cell encapsulation and release. , 2012, Journal of the American Chemical Society.

[15]  P. Gatenholm,et al.  3D Bioprinting Human Chondrocytes with Nanocellulose-Alginate Bioink for Cartilage Tissue Engineering Applications. , 2015, Biomacromolecules.

[16]  Elisabetta A. Matsumoto,et al.  Biomimetic 4D printing. , 2016, Nature materials.

[17]  A. Schenning,et al.  Humidity-responsive liquid crystalline polymer actuators with an asymmetry in the molecular trigger that bend, fold, and curl. , 2014, Journal of the American Chemical Society.

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

[19]  Kai Yang,et al.  Stimuli responsive drug delivery systems based on nano-graphene for cancer therapy. , 2016, Advanced drug delivery reviews.

[20]  Shannon E Bakarich,et al.  4D Printing with Mechanically Robust, Thermally Actuating Hydrogels. , 2015, Macromolecular rapid communications.

[21]  Ali Khademhosseini,et al.  Coaxial extrusion bioprinting of 3D microfibrous constructs with cell-favorable gelatin methacryloyl microenvironments , 2018, Biofabrication.

[22]  Ali Khademhosseini,et al.  Interdigitated array of Pt electrodes for electrical stimulation and engineering of aligned muscle tissue. , 2012, Lab on a chip.

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

[24]  Karen Abrinia,et al.  Surface acoustic waves induced micropatterning of cells in gelatin methacryloyl (GelMA) hydrogels , 2017, Biofabrication.

[25]  Zhengguo Zhang,et al.  A multi-controlled drug delivery system based on magnetic mesoporous Fe3O4 nanopaticles and a phase change material for cancer thermo-chemotherapy , 2017, Nanotechnology.

[26]  J. F. Poyatos,et al.  On the search for design principles in biological systems. , 2012, Advances in experimental medicine and biology.

[27]  Bing Chen,et al.  3D bioprinting of BMSC-laden methacrylamide gelatin scaffolds with CBD-BMP2-collagen microfibers , 2015, Biofabrication.

[28]  Yang Yang,et al.  Multi-stimuli responsive and multi-functional oligoaniline-modified vitrimers† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc02855a Click here for additional data file. , 2016, Chemical science.

[29]  Hajime Shigemitsu,et al.  Design Strategies of Stimuli-Responsive Supramolecular Hydrogels Relying on Structural Analyses and Cell-Mimicking Approaches. , 2017, Accounts of chemical research.

[30]  Yan Zhang,et al.  3D Printed Graphene Based Energy Storage Devices , 2017, Scientific Reports.

[31]  Guifang Gao,et al.  Accelerated myotube formation using bioprinting technology for biosensor applications , 2012, Biotechnology Letters.

[32]  Peter Pivonka,et al.  Handheld Co-Axial Bioprinting: Application to in situ surgical cartilage repair , 2017, Scientific Reports.

[33]  María López-Valdeolivas,et al.  4D Printed Actuators with Soft-Robotic Functions. , 2018, Macromolecular rapid communications.

[34]  Ali Khademhosseini,et al.  Electrical stimulation as a biomimicry tool for regulating muscle cell behavior , 2013, Organogenesis.

[35]  Elbadawy A. Kamoun,et al.  L-Arginine grafted alginate hydrogel beads: A novel pH-sensitive system for specific protein delivery , 2015 .

[36]  V. Khutoryanskiy,et al.  Designing temperature-responsive biocompatible copolymers and hydrogels based on 2-hydroxyethyl(meth)acrylates. , 2008, Biomacromolecules.

[37]  L. Poole-Warren,et al.  Conducting polymer-hydrogels for medical electrode applications , 2010, Science and technology of advanced materials.

[38]  Akhilesh K. Gaharwar,et al.  Nanoengineered thermoresponsive magnetic hydrogels for biomedical applications , 2016, Bioengineering & translational medicine.

[39]  Joong Tark Han,et al.  3D Printing of Reduced Graphene Oxide Nanowires , 2015, Advanced materials.

[40]  Yanju Liu,et al.  Direct-Write Fabrication of 4D Active Shape-Changing Structures Based on a Shape Memory Polymer and Its Nanocomposite. , 2017, ACS applied materials & interfaces.

[41]  Shir Shapira,et al.  4D Printing of Shape Memory-Based Personalized Endoluminal Medical Devices. , 2017, Macromolecular rapid communications.

[42]  Jun Ni,et al.  A review of 4D printing , 2017 .

[43]  U. Demirci,et al.  Guided and magnetic self-assembly of tunable magnetoceptive gels , 2014, Nature Communications.

[44]  Xue Li,et al.  Stimuli-responsive polymers and their applications , 2017 .

[45]  Martin Möller,et al.  In‐Gel Direct Laser Writing for 3D‐Designed Hydrogel Composites That Undergo Complex Self‐Shaping , 2017, Advanced science.

[46]  Y. S. Zhang,et al.  Electrically Driven Microengineered Bioinspired Soft Robots , 2018, Advanced materials.

[47]  Savas Tasoglu,et al.  Paramagnetic Levitational Assembly of Hydrogels , 2013, Advanced materials.

[48]  S Sánchez,et al.  Applications of three-dimensional (3D) printing for microswimmers and bio-hybrid robotics. , 2015, Lab on a chip.

[49]  Gordon G Wallace,et al.  Inkjet printable polyaniline nanoformulations. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[50]  Edgar Yong Sheng Tan,et al.  A Mathematical Model on the Resolution of Extrusion Bioprinting for the Development of New Bioinks , 2016, Materials.

[51]  Boyang Zhang,et al.  Organ‐On‐A‐Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies , 2018, Advanced healthcare materials.

[52]  Y. S. Zhang,et al.  Microfluidics‐Enabled Multimaterial Maskless Stereolithographic Bioprinting , 2018, Advanced materials.

[53]  D. Kelly,et al.  Tuning Alginate Bioink Stiffness and Composition for Controlled Growth Factor Delivery and to Spatially Direct MSC Fate within Bioprinted Tissues , 2017, Scientific Reports.

[54]  N. Gallant,et al.  Protein-surface interactions on stimuli-responsive polymeric biomaterials , 2016, Biomedical materials.

[55]  L. Ionov,et al.  Temperature controlled encapsulation and release using partially biodegradable thermo-magneto-sensitive self-rolling tubes , 2010 .

[56]  Cansel Tuncer,et al.  pH-Responsive polymers , 2017 .

[57]  P. F. Vasconcelos,et al.  In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus , 2018, Scientific Reports.

[58]  R L Reis,et al.  Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering. , 2006, Journal of nanoscience and nanotechnology.

[59]  Shoji Takeuchi,et al.  Cell Origami: Self-Folding of Three-Dimensional Cell-Laden Microstructures Driven by Cell Traction Force , 2012, PloS one.

[60]  Kostas Kostarelos,et al.  Electroresponsive Polymer–Carbon Nanotube Hydrogel Hybrids for Pulsatile Drug Delivery In Vivo , 2013, Advanced healthcare materials.

[61]  A. Studart,et al.  Multimaterial magnetically assisted 3D printing of composite materials , 2015, Nature Communications.

[62]  Philippe Menasché,et al.  A 3D magnetic tissue stretcher for remote mechanical control of embryonic stem cell differentiation , 2017, Nature Communications.

[63]  Jong-Oh Park,et al.  Magnetic actuated pH-responsive hydrogel-based soft micro-robot for targeted drug delivery , 2016 .

[64]  Amir Hosein Sakhaei,et al.  Multimaterial 4D Printing with Tailorable Shape Memory Polymers , 2016, Scientific Reports.

[65]  Nureddin Ashammakhi,et al.  Stimuli-Responsive Biomaterials: Next Wave. , 2017, The Journal of craniofacial surgery.

[66]  Leonid Ionov,et al.  4D Biofabrication Using Shape‐Morphing Hydrogels , 2017, Advanced materials.

[67]  P. Ajayan,et al.  Three-Dimensional Printed Graphene Foams. , 2017, ACS nano.

[68]  Hamidreza Arandiyan,et al.  Lanthanide‐Doped Upconversion Nanoparticles: Emerging Intelligent Light‐Activated Drug Delivery Systems , 2016, Advanced science.

[69]  Stephen Beirne,et al.  Three dimensional (3D) printed electrodes for interdigitated supercapacitors , 2014 .

[70]  Atsushi Harada,et al.  Preparation of dual-stimuli-responsive liposomes using methacrylate-based copolymers with pH and temperature sensitivities for precisely controlled release. , 2017, Colloids and surfaces. B, Biointerfaces.

[71]  James A Bankson,et al.  Three-dimensional tissue culture based on magnetic cell levitation. , 2010, Nature nanotechnology.

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

[73]  Skylar Tibbits,et al.  4D Printing: Multi‐Material Shape Change , 2014 .

[74]  Murugan Ramalingam,et al.  Applications of carbon nanotubes in stem cell research. , 2014, Journal of biomedical nanotechnology.

[75]  Jun Yang,et al.  3D Printing/Interfacial Polymerization Coupling for the Fabrication of Conductive Hydrogel , 2018 .

[76]  Ali Khademhosseini,et al.  3D biofabrication strategies for tissue engineering and regenerative medicine. , 2014, Annual review of biomedical engineering.

[77]  M. Radisic,et al.  Moldable elastomeric polyester-carbon nanotube scaffolds for cardiac tissue engineering. , 2017, Acta biomaterialia.

[78]  Karsten Haupt,et al.  Rapid Prototyping of Chemical Microsensors Based on Molecularly Imprinted Polymers Synthesized by Two‐Photon Stereolithography , 2016, Advanced materials.

[79]  Xin Qian,et al.  A 3D Self‐Shaping Strategy for Nanoresolution Multicomponent Architectures , 2018, Advanced materials.

[80]  Nicholas A Peppas,et al.  Multi-responsive hydrogels for drug delivery and tissue engineering applications , 2014, Regenerative biomaterials.

[81]  A. Ravindran,et al.  Novel Electrically Conductive Porous PDMS/Carbon Nanofiber Composites for Deformable Strain Sensors and Conductors. , 2017, ACS applied materials & interfaces.

[82]  Zhigang Suo,et al.  Ultrasound-triggered disruption and self-healing of reversibly cross-linked hydrogels for drug delivery and enhanced chemotherapy , 2014, Proceedings of the National Academy of Sciences.

[83]  Ritu Raman,et al.  Optogenetic skeletal muscle-powered adaptive biological machines , 2016, Proceedings of the National Academy of Sciences.

[84]  Ramesh Raskar,et al.  Active Printed Materials for Complex Self-Evolving Deformations , 2014, Scientific Reports.

[85]  Geoffrey M. Spinks,et al.  Microstructures of conducting polymers: Patterning and actuation study , 2013 .

[86]  Murugan Ramalingam,et al.  The use of microtechnology and nanotechnology in fabricating vascularized tissues. , 2014, Journal of nanoscience and nanotechnology.

[87]  Milica Radisic,et al.  Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment. , 2016, Tissue engineering. Part B, Reviews.

[88]  Ali Khademhosseini,et al.  Smart scaffolds in tissue regeneration , 2018, Regenerative biomaterials.

[89]  Ali Khademhosseini,et al.  Electrically regulated differentiation of skeletal muscle cells on ultrathin graphene-based films , 2014 .

[90]  Mehmet Remzi Dokmeci,et al.  Three-Dimensional Bioprinting of Functional Skeletal Muscle Tissue Using Gelatin Methacryloyl-Alginate Bioinks , 2019, Micromachines.

[91]  Qingzhen Yang,et al.  Perspective: Fabrication of integrated organ-on-a-chip via bioprinting. , 2017, Biomicrofluidics.

[92]  M. Zrínyi,et al.  Magnetic Field-Responsive Smart Polymer Composites , 2007 .

[93]  B. Jeong,et al.  Temperature-responsive compounds as in situ gelling biomedical materials. , 2012, Chemical Society reviews.

[94]  J Cheeke Fundamentals and Applications of Ultrasonic Waves, Second Edition , 2012 .

[95]  Manish K Jaiswal,et al.  Injectable nanoengineered stimuli-responsive hydrogels for on-demand and localized therapeutic delivery. , 2017, Nanoscale.

[96]  Caterina Credi,et al.  3D Printing of Cantilever-Type Microstructures by Stereolithography of Ferromagnetic Photopolymers. , 2016, ACS applied materials & interfaces.

[97]  Atsushi Harada,et al.  Dual-stimuli responsive liposomes using pH- and temperature-sensitive polymers for controlled transdermal delivery , 2017 .

[98]  Tobin E. Brown,et al.  Spatiotemporal hydrogel biomaterials for regenerative medicine. , 2017, Chemical Society reviews.

[99]  Christopher G. Langhammer,et al.  Skeletal myotube integration with planar microelectrode arrays in vitro for spatially selective recording and stimulation: A comparison of neuronal and myotube extracellular action potentials , 2011, Biotechnology progress.

[100]  Christopher S. Chen,et al.  Cells lying on a bed of microneedles: An approach to isolate mechanical force , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[101]  Patricia Limousin,et al.  Graphene‐Based Electroresponsive Scaffolds as Polymeric Implants for On‐Demand Drug Delivery , 2014, Advanced healthcare materials.

[102]  Feng Xu,et al.  Bioprinting 3D cell-laden hydrogel microarray for screening human periodontal ligament stem cell response to extracellular matrix , 2015, Biofabrication.

[103]  Charlie C. L. Wang,et al.  Four-Dimensional Printing for Freeform Surfaces: Design Optimization of Origami and Kirigami Structures , 2015 .

[104]  Rashid Bashir,et al.  In Situ Self‐Folding Assembly of a Multi‐Walled Hydrogel Tube for Uniaxial Sustained Molecular Release , 2013, Advanced materials.

[105]  Qingzhen Yang,et al.  Bioprinting-Based PDLSC-ECM Screening for in Vivo Repair of Alveolar Bone Defect Using Cell-Laden, Injectable and Photocrosslinkable Hydrogels. , 2017, ACS biomaterials science & engineering.

[106]  Charles M Lieber,et al.  Advances in nanowire bioelectronics , 2017, Reports on progress in physics. Physical Society.

[107]  Jason A Burdick,et al.  Three-dimensional extrusion bioprinting of single- and double-network hydrogels containing dynamic covalent crosslinks. , 2018, Journal of biomedical materials research. Part A.

[108]  Jinsong Leng,et al.  Mechanisms of multi-shape memory effects and associated energy release in shape memory polymers , 2012 .

[109]  Milica Radisic,et al.  Flexible shape-memory scaffold for minimally invasive delivery of functional tissues. , 2017, Nature materials.

[110]  Jaroslav Stejskal,et al.  Conducting polyaniline based cell culture substrate for embryonic stem cells and embryoid bodies , 2015 .

[111]  Pinar Zorlutuna,et al.  Enabling personalized implant and controllable biosystem development through 3D printing. , 2018, Biotechnology advances.

[112]  Feng Xu,et al.  4D Bioprinting for Biomedical Applications. , 2016, Trends in biotechnology.

[113]  George John,et al.  A renewable resource-derived thixotropic self-assembled supramolecular gel: magnetic stimuli responsive and real-time self-healing behaviour , 2015 .

[114]  ChoiJin,et al.  4D Printing Technology: A Review , 2015 .

[115]  N. Ashammakhi,et al.  Nanosize, mega-impact, potential for medical applications of nanotechnology. , 2006, The Journal of craniofacial surgery.