Medication developers have for a long time already been talking about the connection between individual diagnosis and drug administration adjusted to this – the personalised medicine of the future. But can such a thing work in medical technology? Is it possible to tailor hip joint, stent or tissue replacement to individual patients without grinding, drilling or employing time-consuming cell cultures so that they will fit in properly? The answer to this question comes from a method that has long been used to deliver prototype models before series production begins in fields outside of medicine: 3D printing.
As good as the original
There are places where printed tissue can utilise its advantages – such as those where receiving blood supply from a highly branched vascular system is not the crucial element. In April this year an international working group published construction plans for a new type of cartilage tissue. Its physical properties, ie. elasticity and resistance to mechanical loads, come very close to those of the natural model of the knee. The structure also provides chondrocytes with a new home. Using “melt electrospinning writing”, very thin fibres are braided in a hydrogel. Depending on requirements, these fibres made from PCL (poly-ε-caprolactone) provide tissue with peak values strengths that have until now more or less hardly ever been reached. At the same time however, it is resilient and retains its shape even after intensive mechanical stress. Initial studies with implanted chondrocytes have shown that the cells retain not only their morphology, but also their function, and they react to pressure load by altering gene expression. After a few years, the body will have entirely dismantled the artificial braid and ideally should have replaced it via its own tissue production. Studies in the clinic should begin shortly.
It’s not only orthopaedic surgeons who might well need to employ such tissue replacement, but also surgeons from other disciplines. Co-author Dietmar Hutmacher currently conducts research in Munich and can also foresee its applications in the reconstruction of the female breast or the repair of heart tissue. “We need to implant the structure under the muscle,” says Hutmacher, and the reinforced fibre tissue would be able to trigger the “regeneration both of large amounts of breast tissue as well as biodynamically heavily stressed heart valves”.
Tissue engineered supports for weak airways
Another application of such 3D matrices was published in Science Translational Medicine by researchers from the Ann Arbor University in Michigan in May this year. They showed that the pressure of implants helps not only adults but also children in whom the aid needs to be able to grow. In young patients with tracheo-bronchomalacia the connective tissue of the large airways is so weak that it collapses repeatedly during breathing. Previously a tracheotomy involving mechanical ventilation was the choice available to these children, although associated with a high complication rate. Respiratory arrest and the consequences for the heart and circulation often lead to growth impairment or even death.
Used in three patients between three and sixteen months of age, a scaffold enveloping the main bronchi externally and sewn onto them has now proven its worth. Thanks to its open cylindrical shape, it grows in synchrony with the size increase of the respiratory tract. Here, too, the material (PCL) dissolves after a few years, when the connective tissue is strong enough to withstand the pressure loads itself. According to the precise data from previous CT scans, a 3D printer ensures a customised design adapted to respiratory support.
From hearing device to the printed organ
Particularly in paediatrics the specific advantages of printed parts can utilise either via mass production or through laborious manual work. Based on measurements via imaging techniques, they can be made to measure within a few days by the printer. Depending on requirements, the product consists of various materials. Scientists from Oxford reported as early as 2013 about a micelle-fabric which they printed using water droplets on a greasy surface. Together with liposomes from cells, the tissue was able to exchange signals, to contract – thus changing its shape.
In the area of dentistry doctors have publicised the use of a printed backbone and the use of growth factors in a case of root canal treatment involving a large defect. After a year, healing had gone well.
The list of products emerging from the printer for medical use is getting ever longer: from bone implants to lenses, anatomical organ models to pharmaceutical technology. There the active agents – printed in one individual patient’s dosage form – suit the patient’s needs better than tablets in the standard package. Hearing instruments, with their shape being matched to the individual anatomy of their user, are today almost 100 percent of the time produced by the printer. With stem cells or differentiated organ cells, small model tissue can be quickly and cheaply produced which is good for personalised pharmacological drug testing. Employing a suitably designed model ensures that the print head does not affect the viability of cells. This opens up perspectives in regenerative medicine ranging through to the printed organ.
Dispensing vascular system from a spray head
When the aim is to have connective tissue which is also not too thick, such as that in cartilage, printers now no longer have problems building multi-layered complex structures as well. Problems arise with organs requiring a nutrient supply and waste disposal vascular system of 150-200 micron thickness. Integrating such vascular systems in the tissue has until recently been considered an extremely high hurdle. Scientists from Harvard, Stanford and in Sydney have now indicated that they have incorporated a functioning capillary network into printed fabrics.
Printer-derived models have in the meantime helped surgeons to remove the smallest metastases from the liver, to replace cranial bone after trauma and produce jawbone from titanium powder within a short time. All these applications have thus far been individual cases. Before a tissue printer does regular service in the hospital or in the doctor’s practices, studies conducted on a larger number of patients and with long-term observations have to show that the method and materials are permanently safe and functional.
Do-it-yourself medical technology?
Finally, it could also happen that, given financial need, a do-it-yourself process for producing the required human spare parts will develop. To what extent such competition can contribute to improving quality at an affordable price is as difficult to predict as is the possible misuse of technology.
Thus far around eleven million dollars has flowed into the medical development of 3D printing. According to expert opinion, this should significantly change in the coming ten years. Around two billion dollars of investment in hospitals, doctors’ practices and laboratories will then flow into printing technology. Maybe doctors will then be removing stem cells immediately after delivery which can, whenever repairs are required, in later life be differentiated into the organ cells needed and embedded via printing technology into short-term synthesis fabric. A printer which guides repair of damaged tissue via remote control of a lever arm directly in the operating room is for the time being still a vision of the future, but will perhaps soon be reality.