Illuminating heart healing Heart failure, lacking effective treatment, finds hope in a light-driven innovation that promises precise cardiovascular repair. Health © Tom/stock.adobe.com Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity globally, a substantial socio-economic burden. With the ageing population on the rise, the incidence of CVD is projected to increase, alongside heart failure (HF) – the ultimate consequence of many CVDs. HF profoundly impacts quality of life and necessitates caregiver support. Unfortunately, there is currently no effective pharmacological treatment, and it is not possible to reverse disease progress. Thus, a transformative therapeutic approach is urgently needed that can restore cardiac function and systemic blood flow. Optically triggered cardiac repair The EU-funded LION-HEARTED project aims to develop a revolutionary approach for preserving or restoring cardiovascular function, transcending the limitations of current pharmaceutical and electrical stimulation techniques. At the core of this innovative cardiovascular repair strategy is optoceutics, a novel technology utilising optical stimuli to modulate biological processes without resorting to gene manipulation. Optoceutics operates at cell, tissue and whole organ levels and overcomes long-term safety concerns, unlocking novel avenues for cardiovascular translation opportunities. LION-HEARTED aims to harness light to directly stimulate the regenerative potential of resident cardiac progenitors, cardiomyocytes and circulating endothelial cells homing towards the heart following an ischaemic insult. “Since cells are largely transparent to visible light, it is necessary to use photoactive materials as transducers, able to convert the information carried by light into modulation of the biological system,” explains project coordinator Maria Rosa Antognazza, a researcher at Istituto Italiano di Tecnologia in Milan, Italy. The LION-HEARTED approach The technological cornerstone of LION-HEARTED is based on biocompatible conjugated polymers, inherently sensitive to visible light and engineered to optically modulate the activity of both cardiac and endothelial cells. This distinctive advantage lies in the ability of light to target these specific cell sub-populations reversibly and selectively, thereby triggering the biological pathways crucial for cardiac repair. “The LION-HEARTED approach offers unparalleled spatiotemporal resolution, lower invasiveness and higher selectivity compared to traditional methods,” highlights Antognazza. The project goes well beyond the current state-of-the-art to combine optical stimulation and nanotechnology for the first time in the treatment of CVDs. The journey of technological advances LION-HEARTED has achieved significant milestones in material synthesis, validating the approach both in vitro and in vivo using mouse and pig models. Through thin films of photoactive materials, researchers enhanced angiogenesis with remarkable reliability and efficacy. These films demonstrated the capacity to optically control the activity of cardiomyocytes and regulate their beating properties. For in vivo applications, injectable materials coupled with wireless-controlled light sources were engineered and their biocompatibility confirmed. When used in pig disease models, they generated promising results. Overall, the innovative approach of LION-HEARTED holds immense promise in transforming cardiovascular treatments and positively impacting the lives of millions affected by HF. Moreover, the recent COVID-19 health crisis has underscored the potential therapeutic significance of LION-HEARTED. Despite being primarily a respiratory disease, COVID-19 presents extrapulmonary manifestations and individuals with pre-existing cardiovascular comorbidities experience more adverse clinical outcomes when infected by the SARS-CoV-2 virus. LION-HEARTED stands poised to address this need, with future endeavours focusing on material engineering and exploring broader application potentials in clinically relevant conditions. Keywords LION-HEARTED, photoactive materials, heart failure, cardiovascular disease, optoceutics, cardiomyocytes, nanotechnology, angiogenesis
