Browsing by Author "SOUSA, MARIA CAROLINA MAIA LOPES SALGADO DE"
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- Understanding the influence of shear stress and support cells (MSC) to engineer vascularized units for tissue engineering applicationsPublication . SOUSA, MARIA CAROLINA MAIA LOPES SALGADO DE; Ribeiro, Maria Cristina Castro; Salgado, Christiane LaranjoImpaired healing of chronic wounds remains a major challenge for healthcare systems due to the complexity of restoring functional vascular networks. Current therapies are limited, highlighting the need for new strategies to promote vascularization and tissue regeneration. The present work investigates how biomaterials, cellular heterotypic systems, and biomechanical stimulation can be combined to support the development of stable and functional vascular networks. Bi-cultured spheroid were developed based on stromal and endothelial cells and showed a critical role of mesenchymal stem cells (MSCs) in supporting endothelial colony forming cells (ECFCs) organization through extracellular matrix (ECM) deposition and pro-angiogenic signalling. Early-stage spheroids exhibited the highest metabolic activity and were therefore selected for the subsequent studies. Fibrin hydrogels provided a suitable environment for cellular growth and angiogenic sprouting but showed contraction after seven days due to MSC-mediated degradation. GelMA, being softer, with higher degradation rate, lost structural integrity, preventing ECFC elongation outside the spheroid core. Microfluidic experiments further revealed that laminar flow (shear stress) strongly influenced outcomes. Flow rates of 15–20 μL/min promoted vessel elongation, increased network complexity, and improved stability and maturation, particularly in spheroids with higher rate of MSCs. Together, these findings establish a framework for advancing vascularized tissue constructs toward regenerative applications.