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Tomasina, C.

Publications and source records attributed to Tomasina, C..

2 recordsLinked to original sources

Wave-inspired MEW scaffolds for enhanced ligament tissue regeneration

AO_SCPLOWBSTRACTC_SCPLOWLigament injuries remain a major clinical challenge due to the limited intrinsic healing capacity of these fibrous tissues. Here, we demonstrate the use of melt electrowriting (MEW) to fabricate poly({varepsilon}-caprolactone) (PCL) scaffolds with precisely engineered wave architectures that mimic the hierarchical organization and nonlinear mechanics of native ligaments. By tuning fiber geometry, we achieved scaffolds with distinct mechanical behaviors ranging from highly compliant to structurally resilient, enabling architecture-driven modulation of elastic modulus and fatigue response. Mechanical testing revealed that wave-patterned scaffolds dissipate energy efficiently and adapt structurally under cyclic loading, reproducing key features of ligament-like viscoelasticity. When cultured with human anterior cruciate ligament (ACL) cells, the scaffolds supported adhesion, proliferation, and spatially organized alignment, together with the expression of ligament-associated markers. The results demonstrate that MEW scaffolds provide a favorable environment for ligament cell adhesion and matrix synthesis, while highlighting the strong influence of geometry on cell organization and early matrix production. Overall, this study establishes wave-based MEW architectures as a versatile platform to guide ligament tissue formation.

bioengineering↗

3D soft hydrogels induce human mesenchymal stem cells "deep" quiescence

Human mesenchymal stem/stromal cells (hMSCs) present a great opportunity for tissue regeneration due to their multipotent capacity. However, when cultured on 2D tissue culture polystyrene (TCPS) plates, hMSCs lose their differentiation capacity and clinical potential. It has been reported that cells need a more physiologically relevant micro-environment that allows them to maintain their phenotype. Here, we have developed a 3D alginate hydrogel functionalized with the Arg-Gly-Asp (RGD) sequence and having low mechanical stiffness that mimics the mechanical properties (>5 KPa) of bone marrow. hMSCs cultured in these hydrogels appeared to be halted in G1 phase of the cell cycle and to be non-proliferative, as shown by flow cytometry and 5-Ethynyl-2-deoxyuridine (EdU) staining, respectively. Their quiescent state was characterized by an upregulation of enhancer of zeste homolog 1 (EZH1) at the gene level, forkhead box O3 (FoxO3) and cyclin-dependent kinase inhibitor 1B (p27) at the gene and protein levels compared to hMSCs grown in 2D TCPS. Comparative studies in 3D hydrogels of alginate-RGD presenting higher concentration of the peptide or in collagen hydrogels revealed that independently of the concentration of RGD or the chemistry of the adhesion motives, hMSCs cultured in 3D presented a similar phenotype. This quiescent phenotype was exclusive of 3D cultures. In 2D, even when cells were starved of fetal bovine serum (FBS) and became also non-proliferative, the expression of these markers was not observed. We propose that this difference may be the result of mammalian target of rapamycin complex 1 (mTORC1) being downregulated in hMSCs cultured in 3D hydrogels, which induces cells to be in "deep" quiescence and be kept alive ex vivo for a long period of time. Our results represent a step forward towards understanding hMSCs quiescence and its molecular pathways, providing more insight for hMSCs cell therapies.

bioengineering↗