3D printing: Innovations shaping the future of biotech

3D printing, or additive manufacturing, is the automated layering of materials, based on computerised models, to build up a three-dimensional structure. There are several well established industrial and commercial applications, ranging from aerospace parts manufacture to making simple jewellery. In biotech, this technology hit the headlines in early 2012 when a printed titanium jaw bone was successfully implanted into an elderly patient. Printing of organic materials, and even living cells, is a new and advancing technology, which is being used for organ bio-engineering, and the quest to create functional organs for transplantation.

Replacement bones

Hailed as a first of its kind, February saw an announcement from the University of Hasselt, Belgium, and 3D printing company LayerWise, describing an 83 year old Belgian woman with a chronic lower jaw infection who successfully received a custom-printed complete titanium replacement.  Previously, only a partial jaw replacement had been achieved. The exact geometric match, achieved through an MRI scan of the woman’s infected jaw, enabled surgeons to more quickly undertake the operation and without complications compared with traditional reconstructive surgery. Once designed, the implant was printed in a matter of hours and allowed for normal chewing, talking, and swallowing.

More sophisticated implants are already on the horizon. Announced last year, and published in February 2012, a team from Washington State University created a porous ceramic scaffold by 3D printing, designed to promote de novo production of bone growth within the framework. They found that addition of silica and zinc oxide to the ceramic scaffold—natural components of bone—provided increased strength and promoted improved cell proliferation compared to normal ceramic scaffolds. This technology allows an implant with a more natural weight and density to be used, although animal testing is yet to be carried out.

Innovations in organ engineering

Approximately 74, 000 Americans are on the organ transplant waiting list, and demand far outweighs supply. Organ specific stem cells—derived from the patient, or from embryonic stem cells—can potentially be expanded in culture to provide the building blocks for a replacement organ, such as a kidney or liver. The challenge lies in assembling these cells in the correct framework and with sufficient vasculature in order to function and survive. Bioprinting is a recent technology that uses small aggregates of living cells as the “ink” to construct 3D tissues to any given design. However, problems have arisen in vascularising larger structures (although advances in this area are progressing). Without extensive vascularisation, cells become necrotic at the centre of the structure due to a lack of oxygen and nutrient supply, and build-up of waste products. Organovo, a San Diego based company, has led the bioprinting charge with its NovoGen MMX Bioprinter and is currently printing human cells to create more physiologically relevant 3D culture systems for drug discovery and research. Going forward, the company aims to print viable tissue for partial or whole organ replacement.

In July, a team from the University of Pennsylvania published a report in the journal Nature Materials describing their design of a 3D printed lattice of carbohydrate glass filaments. Specialised endothelial cells can adhere to these filaments and form a functioning blood vessel network. The filaments are supported within an extracellular matrix (ECM)-like gel mould, which is capable of housing organ specific cells that can grow around the vasculature. The filaments themselves are sugar-based   and so can be easily dissolved, leaving only the living tissue behind. This network of engineered vessels was able to sustain the passage of blood delivered in pulses and at pressure, akin to normal blood flow. As proof of principle, primary rat hepatocytes (specialised liver cells) were able to carry out their normal metabolic functions when housed in the ECM gel and when supplied with blood through the vessel network, without which the survival and liver-like functions of the cells was significantly diminished.

Professor Christopher Chen, who led the research, told the press, “This new platform technology, from the cell’s perspective, makes tissue formation a gentle and quick journey, because cells are only exposed to a few minutes of manual pipetting and a single step of being poured into the moulds before getting nourished by our vascular network.”

More recently in August, a nanoengineering team led by Professor Shaochen Chen from the Jacobs School of Engineering at the University of California, San Diego, published a study describing a new 3D “biofabrication” technique they call Dynamic Optical Projection Stereolithography. The technique allows direct printing of biocompatible hydrogels (capable of housing living cells), complete with vascular network template; all in a matter of seconds! The vascular networks were successfully infused with human umbilical vein endothelial cells, which proliferated, survived and maintained their identity. This technique involves the use of photosensitive biopolymers that solidify under a light source directed by micromirrors, and is considerably faster than other, previously described biofabrication techniques.

While we are still perhaps decades away from fully functioning bioengineered human organs, these latest innovations in solving the inherent vascularisation problems of these tissues marks a significant milestone in the journey towards bringing this technology closer to reality and to the thousands of patients who could benefit.