Bone fracture with delay or failure to heal is a condition with huge health impact. Although only a small proportion of long bone fractures evolve to non-union (5%), it is a first magnitude problem due to the number of new annual fractures and increasing incidence of complex fractures with high risk of non-consolidation, need for repeated procedures and years of patient disability. Bone autografts, autologous mesenchymal cells, or other complex interventions are used in this setting. The aim of this project is the development of a universal therapy for fractures with delay or failure to heal, aiming to a simple and wide access to allogenic cell therapy combined with biomaterial, in a broad number of patients. Rather than considering ATMP only as a last solution in established non-union fractures, this project advocates that the indication should be moved to an earlier timepoint. Patients will be treated with the combined ATMP as soon as the need for reoperation is identified due to delayed healing, with or without an added infectious component, to avoid long-term suffering for patients and their relatives, and prevent progression to more severe non-unions, with heavy personal, social and economic costs. This approach is aligned with the real needs of patients and better fits with the usual practice in the EU, where reoperations are performed at 6 months or before, in an attempt to accelerate bone healing and avoid complications. The project will establish a master cell bank for a wide allogenic production with donors selection criteria of bone formation potential. Necessary preclinical and clinical information to support the EU approval of a specific combined ATMP will be obtained. Open access to scientific and regulatory information will be available for other EU medical device companies and cell therapy producers, so in addition to direct clinical benefit to patients and healthcare providers, other developers of combined ATMP products will get benefit.

H2TRAIN proposal is funded on the sixth edition of the Electronic Components and Systems (ECS) Strategic Research and Innovation Agenda (ECS-SRIA) topics and major challenges for enabling digital technologies in holistic health-lifestyle supported by artificial intelligence (AI) networks. Biosensors for e-health and smart tracking of sport and fitness are a class of devices that is dominating the consumer and professional market with an unprecedented growth. Despite the impressive capabilities of recent approaches, several prospective revolutionary improvements are still open points, mainly in relationship with four factors: sensing new biosignals and tracking new activity patterns; improving battery lifetime and energy management for continuous use; and secure, reliable and efficient data analysis with AI algorithms and connectivity with the IoT. H2TRAIN aims at advancing the state of the art in this respect, taking profit from the remarkable properties and synergistic potential of one-dimensional (1D) and two-dimensional (2D) materials (1DM and 2DM), enabling more sensitive, efficient, and miniaturized biosensing capabilities within the established CMOS technology framework. This will contribute to the growth of e-health services assisted by AI and will fortify the development of Internet of Things (IoT) applications in health & wellbeing and digital society. H2TRAIN not only facilitates digital technology but also involves the development of new 1DM and 2DM-based devices for sensing, energy harvesting and supercapacitor storage. These innovations serve to integrate sport and health activities into IoT applications, making them accessible as wearable technology. H2TRAIN combines mature CMOS technology products for health and sport sensing with embedded intelligence as a cross-sectional technology. This combination offers a broad spectrum of technology demonstrators (TD) based on advanced sensors, such as tattoo sweat, C-reactive protein, cortisol and lactate.