Motivated by the enormous potential of hydrogels in regenerative medicine, new biocompatible gelatin-based hybrid hydrogels were developed through a green process using poly(ethylene glycol) diglycidyl ether as a cross-linking agent, adding carrageenan and chitosan polysaccharides to the network to better mimic the hybrid composition of native extracellular matrix. Overall, the hydrogels show suitable structural stability, high porosity and pore interconnectivity, good swellability, and finally, biocompatibility. Their mechanical behavior, investigated by tensile and compression tests, appears to be characterized by nonlinear elasticity with high compliance values, fast stress-relaxation, and good strain reversibility with no sign of mechanical failure for compressive loading–unloading cycles at relatively high deformation levels of 50%. Degradation tests confirm the hydrogel bioresorbability by gradual hydrolysis, during which the structural integrity of both materials is maintained, while their mechanical behavior becomes more and more compliant. Human Umbilical Cord-derived Mesenchymal Stem Cells (hUC-MSCs) were used to test the hydrogels as potential carriers for cell delivery in tissue engineering. hUC-MSCs cultured inside the hydrogels show a homogenous distribution and maintain their growth and viability for at least 21 days of culture, with an increasing proliferation trend. Hence, this study contributes to a further understanding of the potential use of hybrid hydrogels and hUC-MSCs for a wide range of biomedical applications, particularly in soft tissue engineering.

Chronic Myeloid Leukemia (CML) is characterized by the BCR::ABL1 fusion gene, driving uncontrolled myeloid cell proliferation. Furthermore, metabolic dysregulation contributes to disease progression. Despite the efficacy of tyrosine kinase inhibitors (TKIs), unresolved clinical needs persist, necessitating refined preclinical models. This study compared responses of three commonly used CML cell lines (K562, LAMA84, KCL22) to five TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib) and a Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor commonly used in clinical settings. Using morphological assessments, viability and metabolic activity assays, glutamate intake evaluations, and gene expression analyses we observed distinct responses among cell lines. TKIs and STAMP inhibitor treatments showed varying impacts on morphological features, cell viability, metabolic activity, and gene expression profiles, highlighting significant differences in cellular responses. This emphasizes the necessity of considering cellular heterogeneity in CML research. This comprehensive comparison provides valuable insights for refining preclinical models and enhancing translational relevance in CML research and treatment development. Understanding the diverse responses of CML cell lines to TKIs and STAMP inhibitor facilitates the selection of appropriate models for specific research questions, ultimately improving the accuracy and reliability of preclinical studies in CML.

Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core–shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin–chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration.

Skin tissue injuries require careful and specialized management due to the complexity of the healing processes involved. Recent advancements in regenerative medicine are centered around the development of innovative scaffolds that can function as delivery systems to restore the lost tissue functions and properties. This study investigates the fabrication and characterization of two hydrogels: a gelatin‐polyethylene glycol‐chitosan‐glycerol‐based hydrogel (G‐PEG‐CH‐Gly) and a gelatin‐polyethylene glycol‐chitosan‐based hydrogel (G‐PEG‐CH). The biological properties of these scaffolds were assessed in terms of biocompatibility with human mesenchymal stromal cells (hMSCs) derived from bone marrow (BM‐hMSCs) and umbilical cord (UC‐hMSCs). MatriDerm (MD) was used as a positive control for biological evaluation. BM/UC‐hMSCs were differentiated into fibroblastic and keratinocyte lineages in the presence of fetal bovine serum (FBS) or human platelet lysate (HPL), both in two‐dimensional (2D) culture and three‐dimensional (3D) scaffolds. The results indicated that G‐PEG‐CH‐Gly and G‐PEG‐CH were more effective than MD in inducing keratinocyte and fibroblastic differentiation, highlighting their potential role in promoting cell differentiation. Furthermore, UC‐hMSCs exhibited higher expression levels of fibroblast and keratinocyte markers compared to BM‐hMSCs, with the best results achieved with G‐PEG‐CH over G‐PEG‐CH‐Gly and MD. This study suggests that novel CH‐based hydrogels could represent a promising therapeutic strategy for skin wound healing.