During the APACHE project, we have worked intensely and have been able to set up a laboratory in Plasma Medicine, unique in our country for the moment, we have developed and implemented new experimental protocols, established a research team and, most importantly, have been able to accomplish the different objectives set in the project, leading to breakthroughs in the field, and opening of new research areas.
From the scientific point of view, we have worked in the different areas foreseen in the DoA:
i. A more physic-chemical part related to the characterization of plasma sources and their effects in different liquids,
ii. A part related with biomaterials, where a) different polymers in solution have been selected, and the effects of plasmas therein have been evaluated with regard to the generation of RONS, and b)
iii. A more biological-oncological area where we have evaluated the effects of different plasma-treated liquids and hydrogels on a variety of osteosarcoma cells, on 3D models that we have developed within the project, and also in ex-vivo and in vivo models.
The work performed during the development of the project has allowed to reach all the milestones set up in the project:
- M1 & M2: Characterization of the main species of the plasma jets in different conditions, & Comparison between the characteristics of the different plasma sources employed
- M3, M4 & M5: Characterization of main species generated by APP in liquids (water, saline solutions), cell culture media & biomaterials (hydrogels and calcium phosphates)
- M6: Synthesis and physic-chemical characterization of biocompatible polymers. Generation of RONS has been studied for the different biomaterials, and their potential modifications have been characterized by relevant techniques (FTIR, SEM, Rheology) .
- M7 & M8: Synthesis & characterization of CaP biomimetic microspheres & their combination with the biomaterials, and Anticancer drug loading and release from CaP microspheres and from CaP microspheres + hydrogels
- M9 & M10: Determination of the stability and lifetime of APP-liquid generated species blended in the biomaterials
- M11: Correlation of [ROS & RNS] in liquids and biomaterials with their anticancer potential. As a general rule, higher amounts of RONS are related with bone cell toxicity, and we have already been able to intuit a threshold for toxicity or survival for healthy bone cells, which is key for selective therapy in absence of harmful side effects.
- M12: Fundamental description of the lethal effects of APP-treated liquids & vehicles on bone cancer cells. We have made great progress on the description of the possible mechanisms involved in the anticancer effects shown by plasma jet treated liquids on osteosarcoma, as observed by alterations in mitochondria, metabolic activity, protein expression etc.
- M13, M14 : Determination of osteoconductivity of biomaterials APP-liquid-loaded in orthotopic in vivo models & Determination of the antiproliferative efficiency of the APP-liquid based novel therapies designed
The IP generated in the project has been protected with patents, and the results published in high impact journals like Advanced science, Nature Protocols, Free Radical Biology and Medicine, Biomaterials Science, Analytical chemistry, ACS Appl. Mater. Interfaces, etc.
We have also disseminated the results in diferent academic and scientific forums through invited and contributed oral communications, and also more general dissemination to the public through videos, interviews, etc.
