1. We have successfully implemented a simple and cost-effective method to fabricate a model of gut tissue with physiological-resembling anatomic architecture and dimensions that can be easily integrated into standard cell culture platforms. Two microfabrication techniques have been implemented: dynamic photolithography (Castaño et al., Biofabrication 2019; Altay et al., Front. Bioeng. Biotechnol. 2020; G. Altay, PhD thesis 2019) and digital light processing (DLP). This last technique is the basis of an ERC-PoC (GUT3DPLATE) which is currently running to explore the benefits of these substrates into market niches. This has delayed the publication of the results (Torras et al., to be submitted) to guarantee IP protection properly. Our progress in microfabrication of hydrogel materials has also been recognized by being invited to submit a spotlight review paper in ACS Applied Mater. & Interfaces (Vera et al., 2021) and leading a topic in Frontiers in Bioeng. & Biotechnol. (ebook). In addition, I have been invited to present this work in multiple international conferences (ESOF 2018; CRS Annual Meeting 2018 (Award to the best postdoc of the oral delivery group); XXVII International Materials Research Congress - IMRC 2018 (invited presentation); NanoBioConference 2018; NICE Conference 2018, MRS Fall meeting 2020, Biomaterials World Conference 2020 or microTAS 2021, among others).
2. We have demonstrated that intestinal cells cultured on our substrates behave in a more physiological manner than cells grown on conventional substrates. They better recreate the intestinal barrier properties: adherence and invasion capacity of E. coli LF82 pathogenic bacterial (García-Diaz et al., CRS Conference 2019), permeability and drug absorption properties (Castaño et al., Biofabrication 2019) and allow mimicking the interaction between different cell types of the intestinal mucosa (Vila et al., Biofabrication 2020), which is crucial to disease modelling (A. Vila, PhD thesis 2020). To better exploit this result we have established an on-going collaboration with a local hospital (Hospital Vall d’Hebron).
3. We have successfully developed and characterized several hydrogel formulations that can be used as bioinks in light-based applications (Castaño et al., Biofabrication 2019; Vila et al., Biofabrication 2020; Borgheti et al., in preparation). Aside of the scientific dissemination, we have established an agreement with a Spanish company that develops bioprinting instruments (Regemat 3D) to transfer a bioink specific formulation to their product catalogue.
4. Organoid-derived intestinal epithelial cells can grow on our 3D hydrogels and, upon delivering specific molecular gradients through a microfluidic device, cells are compartmentalized thus recreating their position in the in vivo tissue (G. Altay, PhD thesis 2019; Altay et al., 10.1101/2021.12.13.472418; Martinez et al, Biomaterials Conf. 2020; Martinez et al., MRS fall conf. 2020). We have established a protocol to fabricate the scaffold, the device and to “open-up” intestinal organoids onto monolayers (Altay et al. Scie Reports 2019; Altay et al., Bio-protocol 2020).
5. We successfully developed 2D approaches that have proven to be useful technological tools for the study of relevant factors recognized to affect intestinal cell behavior such as the stiffness of the substrate (Comelles et al., Biofabrication 2020), the patterning of relevant biomolecules identified in the intestinal development and homeostasis (Hortigüela et al., Nano Letters 2018; Cutrale et al., Nat. Protocols 2019; E. Larrañaga, PhD thesis 2021) and new 3D set-ups to study epithelial-stromal interactions (Fernández-Majada et al., 10.1101/2021.05.28.446131).
