PORTEFEUILLE

The face is the gateway to a person's soul. Even the slightest deformity of facial features outside the range perceived to be 'normal' can cause sociopsychological problems. Children born with severe cranofacial defects, for example arhinia, hemifacial microsomies or Treacher-Collins syndrome, suffer much more. They need to undergo in excess of twenty operations to correct breathing, hearing, eating and speech function as well as additional procedures to reconstruct contours of the face. To make treatment even more challenging, these syndromes express themselves in varying grades of severity in each patient and in each tissue type, and thus a unique and individualized reconstruction must be planned for each child.
Due to the growth of the face and its complex contours, the procedures to treat these craniofacial syndromes are amongst the most challenging in reconstructive surgery. The surgeries currently rely on the harvest of the patient’s fascial flaps, bone, muscle, fat and skin for reconstruction which poses additional burden on the child.
We propose a unique and high-technology solution for the design and fabrication of individualized craniofacial grafts for children born with craniofacial defects, thus eliminating some of the need for tissue harvesting. The goals of this project are:
1. The development of a statistical shape model which encompasses the naturally occurring variation in facial anatomy and bone structure of healthy, growing children.
2. The design of 3D models to restore nasal and soft tissue structures in patients with craniofacial defects
3. The advanced manufacture of hybrid which are texturally realistic, biocompatible, and mechanically robust.
4. The pre-clinical evaluation of these grafts.

We develop a toolbox of software and biofabrication processing methods and materials which could one day be used to treat children afflicted by these serious craniofacial conditions. These methods may can also be used for patient’s whose face has been deformed by cancer or trauma. An innovative feature of this project is the collaboration between computer scientists, bioengineers, medical doctors and entrepreneurs. Finally, transfer of these design principles to higher education is a big part in the project. Prof Vetter leads an international course on Probabilistic Morphable Shape Models. “Practical Methods in Biofabrication” is a new course being taught by Prof. Zenobi-Wong at ETH Zürich which has been running since 2018. Both courses incorporate findings from this project and thereby strengthen Swiss education in these cutting-edge fields of biofabrication and anatomical computer modelling.

The goals of the project are completely unique. Up until now the only treatment possible for people with severe craniofacial malformations such as a missing nose, are fabrication of silicone prosthesis held to the face through magnetic pins. These implants are never accepted by the wearer as part of their body, but only as a foreign object. Scientific creativity is required in designing the missing or underdeveloped features to enhance the overall aesthetics of the face. Creativity is also required to come up with new combinations of biomaterials (hybrid implants) to fulfill the complex requirements of the surgical site and which may one day be able to grow in size and shape as the child grows. This project combines aesthetics, computer science, material science and processing to achieve innovative medical products. Technically, modelling face surface and soft tissue under the constraint of the skull development of growing children has never been reported and the development of a detailed model of a growing child's face and skull is one of the truly innovative aspects of the the project. Our recent work includes a statistical shape model of a growing skull and the development of novel casting methods which allow patient-specific, yet simple manufacture. These tools will aid immensely in the work of reconstructive surgeons to plan surgical procedures and achieve better aesthetic outcome.

The current results of the project are summarized below.
- We have set up a pipeline to process MRI and CT scans to extract models of a patient’s skull and created a Statistical Shape Model (SSM) of a human children’s skull and nose from a small test set. With the SSM, we are capable of generating models that match the underlying skull’s features and compare them to the patient’s ones.
- The missing/replacement cartilage part of the patient can be created using the above model. A reinforcement structure that fits within the cartilage model has been generated and is rendered to be as thin as possible in order to minimise the amount of reinforcement material. The reinforcement structure can be manufactured using biocompatible titanium alloys (by means of selective laser melting) or biodegradable lactide polymers (using fusion deposition modelling).
- A novel technique to crosslink cell laden hydrogels around the reinforcement structure has been developed. The technique allows generation of large hybrid constructs using enzymatically or ionically crosslinkable hydrogels in under 30 minutes. To perform this, an intermediate mold is manufactured and preloaded with the required ions or enzymes. With respect to traditional casting techniques, diffusion of ions and enzymes is possible from all sides of the construct. The grafts can be manufactured in a sterile way and using pharmacological grade components.
- Casting with chondrocytes and preclinical evaluation with other hydrogels is ongoing. A preliminary in vivo analysis of the metal reinforcement with and without hydrogel embedding was performed showing no reaction from the host’s immune system.

Outlook: For the Statistical Shape model, we are currently looking into how partial data can be incorporated to improve the synthesis capabilities of the model. In the next steps, we also want to incorporate the reinforcement structure directly into the Statistical Shape model.

Tosoratti, E, Guillon, P, Kessel, B, Zenobi-Wong, M Eluting Moulds for Hydrogel Crosslinking, European Patent EP 19169134