3D Printing in Tissue Engineering

Three-dimensional (3D) printing was developed in the early 1990s at MIT by by Sachs, Haggerty, Cima, and Williams.1 It is a freeform fabrication method that uses regular inkjet printheads to fabricate objects by printing binders onto loose powders in a powder bed.2 What can be made in 3D printing depends on what is used as the material which is either simply deposited or fused, and can include such things as plastics, metal, ceramics, or even living cells, which are applied in layers to produce a 3D object.3

The 3D printing process uses 3D computer models from CAD data sets to produce a physical object. The process is also referred to as rapid prototyping (RP), solid free-form technology (SFF), layered manufacturing (LM), additive manufacturing (AM), or computer aided manufacturing (CAM), depending on the kind of production method used.3,4 The primary advantage of this type of rapid prototyping and additive fabrication is that these layers, which correspond to the cross-sections from the CAD model, can create nearly any complex shape.4 This manufacturing of specific parts is done layer-by-layer without any part-specific tooling or dies, which offers unique advantages for part fabrication of small volumes or one of a kind product manufacturing.2 In general, a wide variety of ceramics, metals, polymers, and composites can be processed using 3D printing, though the keys to successful fabrication are binder selection and temperature parameters.2

3D printing has three primary biological applications: its use in prototyping models for surgery; its potential use in custom implants; and its use in bioprinting human tissues and tissue scaffolds.

The usefulness of 3D printing to create rapid prototypes has been utilized in the surgical arena as a tool to aid in presurgical planning using prototype models to simulate complicated surgeries. 3D models of the pelvis, brain, maxillofacial area, spine, heart, and other organs have all been created to aid in diagnosis and treatment planning. The use of this type of custom 3D models can potentially reduce operating time and complications.4

With 3D printing also comes the potential ability to make custom medical devices that are tailored to individual patients and specific clinical needs, though further process optimization is needed to truly accomplish this goal.2 In February of 2012, a woman received the “world’s first 3D printed jaw transplant,” a custom implant made from a scan of her jaw and produced with titanium powder in just a few hours. Coated in ceramic, the implant was heavier than a natural jaw, but otherwise identical in shape and size to her own, though unlike bioprinted tissue it did not have osteogenic properties.5

Bioprinting, the 3D printing of human cells, is on the forefront of 3D printing technology. In the same way that traditional 3D printing uses binders printed onto loose powders, bioprinting uses “bioinks” printed onto powdered extracellular matrix, in a layer-to-layer manner to create a tissue construct with or without scaffold support. Bioinks are defined as any ink formulation useful for printing human cells.6 The most common bioinks are cell-laden hydrogels, decellularized extracellular matrix-based solutions, and cell suspensions. Inorganic binders can sometimes be used for printing on demineralized bone matrixes.

Direct ink writing (DIW) is the primary commercial bioprinting method. It is an extrusion-based printing that, like all additive manufacturing methods, builds the 3D printed model using cross sections. It is capable of handling high viscosity solutions, colloidal suspensions, and hydrogels.6 Inkjet 3D printing is also be suitable for bioprinting, but it has not yet been commercially adopted.6

Current bioprinting techniques allow printing of structures with similar composition to that of human tissue, but we are still a long way from printing truly functional organs. However, simple tissues like bone and cartilage are closer to being able to being able to be successfully printed, and 3D printed demineralized bone products are already in commercial use.2

The advantages of 3D printing for bone engineering comes from the fine control of features including interconnected porosity, lack of contamination from secondary materials, and direct printing abilities with both metallic and ceramic biomaterials.2 Overall, it is a popular and versatile tool that can fabricate scaffolds for bone tissue engineering with defined shapes and controlled, interconnected porous surfaces.2

Unfortunately, low mechanical strength is a major challenge in building porous scaffolds for tissue engineering, and so far 3D printed bone scaffolds have been limited in use to only no- and low-load bearing applications.2 However, studies attempting to build artificial cartilage have been more succesful, and human-derived induced pluripotent stem cells (iPSCs) have been successfully bioprinted into cartilage mimics using a nanofibrillated cellulose (NFC) composite bioink co-printed with human chondrocytes in the lab.7

Adding growth factors or drugs and personalizing implants to individual patients are all possible outcomes of 3D printing technologies. Although much work remains to be done to make 3D printed tissues clinically applicable,2  progress has been rapid and the future potential is very exciting.

You can read more about the emerging applications of bioprinting here: 3D Printed Tissues from Bench to Bedside.


1 Sachs, E. M., Haggerty, J. S., Cima, M. J., Williams, P. A. (1993). Patent Identifier No. 5,204,055. Cambridge, MA: Massachusetts Institute of Technology. Retrieved from: http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN/5204055

2 Bose, S., Vahabzadeh, S., Bandyopadhyay, A. (2013). Bone tissue engineering using 3D printing. Materials Today, 16(12): 496-504. https://doi.org/10.1016/j.mattod.2013.11.017

3 Ventola, C. L. (2014). Medical applications for 3D printing: Current and projected uses. Pharmacy and Therapeutics, 39(10): 704-711. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189697/

4 Rengier, F. Mehndiratta, A., von Tengg-Kobligk, H., Zechmann, C. M., Unterhinninghofen, R., Kauczor, H.-U., & Giesel, F. L. (2010). 3D printing based on imaging data: Review of medical applications. International Journal of Computer Assisted Radiology and Surgery, 5: 335-341.https://doi.org/10.1007/s11548-010-0476-x

5 Dybuncio, M. (2012, February 6). Woman gets world’s first 3D printed jaw transplant. CBS News. Retrieved from https://www.cbsnews.com/news/woman-gets-worlds-first-3d-printed-jaw-transplant/

6 Ji, S. & Guvendiren, M. (2017). Recent advances in bioink design for 3D bioprinting of tissues and organs. Frontiers in Bioengineering and Biotechnology, 5(23). https://dx.doi.org/10.3389%2Ffbioe.2017.00023

7 Nguyen, D., Gagg, D. A., Forsman, A., Ekholm, J., Nimkingratana, P., Brantsing, C., … Simonsson, S. (2017). Cartilage tissue engineering by the 3D bioprinting of iPS cells in a nanocellulose/alginate bioink. Scientific Reports, 7(658). Retrieved from https://www.nature.com/articles/s41598-017-00690-y