Bone organoid generation based on double scaffolding.

Decellularized bone matrix ( is a classic approach in bone tissue engineering based on the removal of bone tissue cells and the calcified phase using chemical, physical o enzymatic agents The resulting matrix preserves its three dimensional structure and biomechanical properties, providing a native microenvironment suitable for osteogenic development However, due to the complexity of the bone structure, with this method has not been possible to obtain an experimentally reproducible bone organoid that sufficiently replicates the bone biology Another approach to generate organoids is the use of hydrogels functionalized with adhesion peptides and morphogenetic proteins that favor the differentiation and osteogenic capacity of the organoid In this work we developed a new bone model based on the combination of hydrogels and DBMs We tested PVA and dextran hydrogels in combination with BMP responsive reporter cell line ( and the long term effect of the RGD peptide addition to hydrogels evaluating osteogenic differentiation by alkaline phosphatase method and luciferase assays We analyze by histology decellularized DBMs combined with dextran hydrogels containing BRITER cells cultured under osteogenic conditions for 3 weeks Our results showed that this double scaffolding is able to support osteogenic differentiation as well as osseointegration, proving its potential for bone organoid generationUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality