WP 5 – IoT TECHNOLOGIES, HANDHELD BIOPRINTING AND SYSTEM INTEGRATION

The ADMAIORA system consists of a number of software products run on a plurality of platforms. The main software components in the project are:  Cloud Server  Patient SmartPhone App  Patient PC Agent  Clinician Web Interface  Knee Brace firmware In addition, these software products communicate with API’s (Application Programming Interface) for ready made products:  Activity Wristband  US imaging system/LIPUS system  Balance device (COP) In this deliverable a description of the software demonstrator is reported, highlighting each component and its function.

In this deliverable, a prototype of a knee brace for treatment monitoring and LIPUS stimulation is presented. The purpose of the knee brace is double: 1. To enable the monitoring of the cartilage healing process through different direct (US imaging of the cartilage), and indirect means (temperature measurements, maximum bending angle of the knee). 2. To enhance the treatment efficacy by exposing the cartilage to a mechanical stimulus through Low-intensity pulsed ultrasound stimulation (LIPUS) that has been shown to promote stem cell differentiation in chondrocytes. The required LIPUS exposure time is assumed to be compatible with a session in which the patient is seated, i.e. a completely wearable stimulation gear is not required since the stimulation does not need to be applied for extended period of time in dynamic conditions. This means that the brace needs to accommodate the ultrasound transducers for LIPUS but not the external power signal generator to drive them. The generator can be embedded in a seat specifically designed to provide the correct knee positioning for the LIPUS stimulation. The brace design is determined by the constraints of the US imaging examination which needs to be thorough, as shown in a preliminary study performed with a professional US radiologist, and by the placement of the ultrasound transducers for the LIPUS stimulation. The clinical examination was performed with a TELEMED echography system with a linear probe. However, due to the limited acoustic window to the condyles, it is not possible to have simultaneously the TELEMED US probe and the LIPUS transducer in place at the same time. Therefore two different accessories have been added to a commercial brace to enable: 1. a complete US imaging examination (with 8 probe arrangements and 3 different positions of the leg) thanks to a positioning guide; 2. LIPUS session in a comfortable position with a transducer holder fixed to the brace. The maximum angulation of the articulation (the angle closest to 180° between the femur and the tibia) is a good indicator of patient condition improvement over time. It has therefore been decided to include a goniometer on the brace to enable a precise measurement of the joint angle. A second important measurement concerns inflammation, which is related to the joint temperature. A pocket has been added to the brace to fit in a skin temperature probe. The brace prototype is still a preliminary design and needs to be further engineered, integrated and validated in real usage on volunteers. A second iteration will be made on the brace design once the results of T6.2 (Bioeffects of LIPUS on the nanocomposite construct) and T4.3 (Investigation of acoustic parameters for in vivo translation) will provide the optimal size, shape and position of the LIPUS transducers.

This deliverable reports a preliminary description of the handheld bioprinting system to be used for delivering the hydrogel containing ASC cells, carbon nanomaterials and piezoelectric particles into cartilage defects, by following a foot-controlled pneumatic printing strategy based on the specifications devised in the deliverable D2.1. Expected results are reported. The concept design for the DEMONSTRATOR covers aspects related to: - Determination of primary extrusion method - Suitable design of the Control Unit to allow driving the extrusion as well as set different working parameters - Definition of the cartridge geometry (i.e. commercially available syringe based solution) - Design of the extrusion tube and tip geometry - Design of a footswitch that will allow to use and to operate the system. The aim is to build a basic system allowing extrusion of the nanocomposite hydrogel in conditions simulating the final application. The assumption is to regulate the speed of extruded material by means of 3 independent channels as well as to allow the switching between different modes (predefined or stored settings) of operation (3 modes for each channel). Fixing working settings for each of mode will be the matter of further investigations. The bioprinting system overview is shown in Figure 1.