Galectin-3 (Gal-3) is a β-galactoside-binding protein that influences various cell functions, including cell adhesion. We focused on the role of Gal-3 as an extracellular ligand mediating cell-matrix adhesion. We used human adipose tissue-derived stem cells and human umbilical vein endothelial cells that are promising for vascular tissue engineering. We found that these cells naturally contained Gal-3 on their surface and inside the cells. Moreover, they were able to associate with exogenous Gal-3 added to the culture medium. This association was reduced with a β-galactoside LacdiNAc (GalNAcβ1,4GlcNAc), a selective ligand of Gal-3, which binds to the carbohydrate recognition domain (CRD) in the Gal-3 molecule. This ligand was also able to detach Gal-3 newly associated with cells but not Gal-3 naturally present on cells. In addition, Gal-3 preadsorbed on plastic surfaces acted as an adhesion ligand for both cell types, and the cell adhesion was resistant to blocking with LacdiNAc. This result suggests that the adhesion was mediated by a binding site different from the CRD. The blocking of integrin adhesion receptors on cells with specific antibodies revealed that the cell adhesion to the preadsorbed Gal-3 was mediated, at least partially, by β1 and αV integrins—namely α5β1, αVβ3, and αVβ1 integrins.

Vascular endothelial growth factor-A₁₆₅ (VEGF-A₁₆₅) and fibroblast growth factor-2 (FGF-2) are currently used for the functionalization of biomaterials designed for tissue engineering. We have developed a new simple method for heterologous expression and purification of VEGF-A₁₆₅ and FGF-2 in the yeast expression system of Pichia pastoris. The biological activity of the growth factors was assessed in cultures of human and porcine adipose tissue-derived stem cells (ADSCs) and human umbilical vein endothelial cells (HUVECs). When added into the culture medium, VEGF-A₁₆₅ stimulated proliferation only in HUVECs, while FGF-2 stimulated the proliferation of both cell types. A similar effect was achieved when the growth factors were pre-adsorbed to polystyrene wells. The effect of our recombinant growth factors was slightly lower than that of commercially available factors, which was attributed to the presence of some impurities. The stimulatory effect of the VEGF-A₁₆₅ on cell adhesion was rather weak, especially in ADSCs. FGF-2 was a potent stimulator of the adhesion of ADSCs but had no to negative effect on the adhesion of HUVECs. In sum, FGF-2 and VEGF-A₁₆₅ have diverse effects on the behavior of different cell types, which maybe utilized in tissue engineering.

Pulmonary hypertension is a cardiovascular disease with a low survival rate. The protein galectin-3 (Gal-3) binding β-galactosides of cellular glycoproteins plays an important role in the onset and development of this disease. Carbohydrate-based drugs that target Gal-3 represent a new therapeutic strategy in the treatment of pulmonary hypertension. Here, we present the synthesis of novel hydrophilic glycopolymer inhibitors of Gal-3 based on a polyoxazoline chain decorated with carbohydrate ligands. Biolayer interferometry revealed a high binding affinity of these glycopolymers to Gal-3 in the subnanomolar range. In the cell cultures of cardiac fibroblasts and pulmonary artery smooth muscle cells, the most potent glycopolymer 18 (Lac-high) caused a decrease in the expression of markers of tissue remodeling in pulmonary hypertension. The glycopolymers were shown to penetrate into the cells. In a biodistribution and pharmacokinetics study in rats, the glycopolymers accumulated in heart and lung tissues, which are most affected by pulmonary hypertension.

Modern tissue engineering requires not only degradable materials promoting cell growth and differentiation, but also vascularization of the engineered tissue. Porous polylactide/polycaprolactone (PLA/PCL, ratio 3/5) foam scaffolds were prepared by a combined porogen leaching and freeze-drying technique using NaCl (crystal size 250–500 µm) and a water-soluble cellulose derivative (Klucel^TM E; 10–100% w/w relative to the total PLA/PCL concentration) as porogens. Scanning electron microscopy, micro-CT, and Brunauer–Emmett–Teller analysis showed that all scaffolds contained a trimodal range of pore sizes, i.e., macropores (average diameter 298–539 μm), micropores (100 nm to 10 μm), and nanopores (mostly around 3.0 nm). All scaffolds had an open porosity of about 90%, and the pores were interconnected. The size of the macropores and the nanoporosity were higher in the scaffolds prepared with Klucel. Nanoporosity increased water uptake by the scaffolds, while macroporosity promoted cell ingrowth, which was most evident in scaffolds prepared with 25% Klucel. Human adipose-derived stem cells co-cultured with endothelial cells formed pre-vascular structures in the scaffolds, which was further enhanced in a dynamic cell culture system. The scaffolds are promising for the engineering of pre-vascularized soft tissues (relatively pliable 10% Klucel scaffolds) and hard tissues (mechanically stronger 25% and 50% Klucel scaffolds).

We compared the applicability of 3D fibrous scaffolds, produced by our patented centrifugal spinning technology, in soft tissue engineering. The scaffolds were prepared from four different biocompatible and biodegradable thermoplastics, namely, polylactide (PLA), polycaprolactone (PCL), poly(3-hydroxybutyrate) (PHB), and poly(1,4-butylene succinate) (PBS) and their blends. The combined results of SEM and BET analyses revealed an internal hierarchically organized porosity of the polymeric micro/nanofibers. Both nanoporosity and capillary effect are crucial for the water retention capacity of scaffolds designed for tissue engineering. The increased surface area provided by nanoporosity enhances water retention, while the capillary effect facilitates the movement of water and nutrients within the scaffolds. When the scaffolds were seeded with adipose-derived stem cells (ASCs), the ingrowth of these cells was the deepest in the PLA/PCL 13.5/4 (w/w) composite scaffolds. This result is consistent with the relatively large pore size in the fibrous networks, the high internal porosity, and the large specific surface area found in these scaffolds, which may therefore be best suited as a component of adipose tissue substitutes that could reduce postoperative tissue atrophy. Adipose tissue constructs produced in this way could be used in the future instead of conventional fat grafts, for example, in breast reconstruction following cancer ablation.

Pulmonary hypertension (PH) remains a devastating cardiovascular disorder with limited targeted treatment. Galectin-3 has emerged as a promising therapeutic target due to its central role in vascular remodeling and inflammation. Galectin-3 exacerbates intimal hyperplasia by influencing endothelial cells through multiple mechanisms. It also contributes to medial hypertrophy and adventitial thickening by activating vascular smooth muscle cells and adventitial fibroblasts. In PH, right ventricular myocardium can be remodeled through galectin-3-mediated activation of cardiac fibroblasts and impaired cardiomyocyte contractility. Galectin-3 also modulates accompanying inflammatory reactions. This review explores the molecular mechanisms of galectin-3 action in PH and evaluates the potential of galectin-3 inhibition as a therapeutic strategy. Targeting galectin-3 represents a novel avenue in PH management but still faces challenges such as drug specificity and clinical efficacy. Future studies should focus on optimizing the structure and performance of galectin-3 inhibitors for clinical application.