RESUMEN
In search of effective therapeutics for breast cancers, establishing physiologically relevant in vitro models is of great benefit to facilitate the clinical translation. Despite extensive progresses, it remains to develop the tumor models maximally recapturing the key pathophysiological attributes of their native counterparts. Therefore, the current study aimed to develop a microsphere-enabled modular approach toward the formation of in vitro breast tumor models with the capability of incorporating various selected cells while retaining spatial organization. Poly (lactic-co-glycolic acid) microspheres (150-200 mm) with tailorable pore size and surface topography are fabricated and used as carriers to respectively lade with breast tumor-associated cells. Culture of cell-laden microspheres assembled within a customized microfluidic chamber allowed to form 3D tumor models with spatially controlled cell distribution. The introduction of endothelial cell-laden microspheres into cancer-cell laden microspheres at different ratios would induce angiogenesis within the culture to yield vascularized tumor. Evaluation of anticancer drugs such as doxorubicin and Cediranib on the tumor models do demonstrate corresponding physiological responses. Clearly, with the ability to modulate microsphere morphology, cell composition and spatial distribution, microsphere-enabled 3D tumor tissue formation offers a high flexibility to satisfy the needs for pathophysiological study, anticancer drug screening or design of personalized treatment.
RESUMEN
Porous scaffolds play a crucial role in bone tissue regeneration and have been extensively investigated in this field. By incorporating a decellularized extracellular matrix (dECM) onto tissue-engineered scaffolds, bone regeneration can be enhanced by replicating the molecular complexity of native bone tissue. However, the exploration of porous scaffolds with anisotropic channels and the effects of dECM on these scaffolds for bone cells and mineral deposition remains limited. To address this gap, we developed a porous polycaprolactone (PCL) scaffold with anisotropic channels and functionalized it with dECM to capture the critical physicochemical properties of native bone tissue, promoting osteoblast cells' proliferation, differentiation, biomineralization, and osteogenesis. Our results demonstrated the successful fabrication of porous dECM/PCL scaffolds with multiple channel sizes for bone regeneration. The incorporation of 100 µm grid-based channels facilitated improved nutrient and oxygen infiltration, while the porous structure created using 30 mg/mL of sodium chloride significantly enhanced the cells' attachment and proliferation. Notably, the mechanical properties of the scaffolds closely resembled those of human bone tissue. Furthermore, compared with pure PCL scaffolds, the presence of dECM on the scaffolds substantially enhanced the proliferation and differentiation of bone marrow stem cells. Moreover, dECM significantly increased mineral deposition on the scaffold. Overall, the dECM/PCL scaffold holds significant potential as an alternative bone graft substitute for repairing bone injuries.
