Journal of Translational Regenerative Medicine

Abstract This editorial sets the stage for the Journal of Translational Regenerative Medicine (JTRM) by highlighting the convergence of diverse disciplines, including biology, engineering, clinical, and surgical sciences. Regenerative medicine inherently demands cross-disciplinary collaboration. True innovation emerges where clinicians, biotechnologists, tissue engineers, pharmacologists, and molecular scientists converge. This breakdown of traditional silos underscores a critical truth: Complex healthcare challenges cannot be solved in isolation. By building bridges across disciplines, JTRM positions itself at the forefront of this integrative movement in biomedical science.

Abstract Background: Three-dimensional (3D) bioprinting presents a promising platform for fabricating tissue-engineered scaffolds with controlled architecture and cellular integration. 
Methods: In this study, alginate (Alg)-based bioinks incorporating varying concentrations of graphene oxide (GO) were evaluated to optimize key bioprinting parameters (Alg concentration, nozzle diameter, and extrusion pressure) for cardiac tissue engineering applications. Bioinks were formulated with 6%, 7%, and 8% (w/v) Alg and GO concentrations ranging from 0 to 2.0 mg/mL. Printability and structural fidelity were assessed using multiple nozzle sizes (22 G and 25 G) and extrusion pressures (0.85–1.4 bar). 
Results: Results indicated that an Alg concentration of 8% provided superior viscosity and shape retention. The 22-G nozzle offered an optimal balance between filament continuity and pore morphology. GO incorporation resulted in thinner filaments and larger pores, with optimal extrusion pressures varying according to GO concentration. 
Conclusion: These findings provide a framework for tailoring bioprinting parameters to improve scaffold performance and effectiveness in cardiac tissue engineering. 

Abstract Background: Excessive production of reactive oxygen species (ROS) is implicated in the pathogenesis of inflammatory and autoimmune disorders, partly through the dysregulation of T cell function. Curcumin and metformin possess well-documented antioxidant and anti-inflammatory properties, yet their combined effects on T cell oxidative stress have not been comprehensively evaluated. 
Methods: Human peripheral blood T cells from healthy donors were treated with curcumin, metformin, or their combination. Intracellular ROS, superoxide, and glutathione (GSH) levels were quantified by flow cytometry. mRNA expression of key oxidative (NOX2) and antioxidant genes (CAT, SOD1, SOD2, NRF2) was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
Results: Both agents significantly decreased ROS levels and increased intracellular GSH compared with untreated cells. Metformin exhibited superior effects, reducing ROS by ~2.5-fold and increasing GSH nearly 3-fold compared to curcumin. Metformin also induced stronger upregulation of NRF2 and SOD2, and greater suppression of NOX2. Co-treatment produced no general synergistic effects on ROS, GSH, or most antioxidant genes, except for a significant synergistic increase in SOD1 expression.
Conclusion: Metformin outperformed curcumin in enhancing antioxidant defenses and suppressing ROS in T cells, whereas combined therapy showed limited interaction, confined to SOD1. These findings support metformin—alone or with curcumin—as a potential candidate for managing oxidative stress–driven immune disorders, warranting further in vivo and clinical evaluation. 

Abstract Background: Calcium phosphate cements (CPCs) are moldable microporous materials widely used for filling bone voids and defects. Introducing macro-porosity into the structure of these cements can enhance the biological functions and the rate of bone formation. 
Methods: In this study, CPCs with different morphologies (non-porous and porous forms) were used as bone fillers. Different amounts of the porogen were used to obtain different macropore diameters. Bone marrow–derived mesenchymal stem cells (MSCs) were obtained from the tibial shaft of Wistar rats. MSC proliferation was assessed using the MTT assay. Real time PCR and analysis of gene expression for genes relevant to osteogenic differentiation of cells loaded on the samples were carried out. For in vivo evaluations, circular holes were created in the proximal epiphysis of the rabbit tibia bone. The holes were filled with non-porous and macroporous CPCs, and histomorphological evaluation was performed at 4 and 8 weeks after the operation. 
Results: The results demonstrated that porous CPC was able to increase alkaline phosphatase activity and the expression of bone-related proteins (osteocalcin, osteopontin, and osteonectin) in MSCs cultured on the surfaces of cements. For in vivo evaluations, circular holes were created in the proximal epiphysis of the rabbit tibia bone. The holes were filled with non-porous and macroporous CPCs and histomorphologically evaluated at 4 and 8 weeks after the operation. The results revealed that, Wwhen the hole was filled with non-porous CPC, a layer of connective tissue with immature woven bone was formed at the surface of the implant without any resorption phenomenon. However, when the defect was filled with porous CPC (average pore diameter of 200 µm), the major part of the cement was resorbed and the resorbed cement was replaced by mature bone trabecula and unmineralized osteoid tissue.
Conclusion: The creation of macroporous cement could significantly improve the osteogenic ability and the active resorption rate of the cement, further associated with bone replacement by the host tissues. 

Abstract Macrophages are pivotal immune cells that exhibit remarkable plasticity, polarizing into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to environmental cues. This process, known as macrophage polarization, plays a critical role in the progression and resolution of various diseases, including cancer, inflammatory disorders, and infections. The emergence of nanomedicine has highlighted the significant interplay between nanoparticles and the immune system, positioning macrophages as a key therapeutic target. This review comprehensively examined the immunomodulatory effects of metal-based nanoparticles—specifically copper, titanium, gold, iron, silver, aluminum, and silicon—on macrophage polarization. We detail how intrinsic nanoparticle properties, such as size, shape, surface chemistry, and composition dictate the polarization outcome by modulating specific molecular pathways, including NF-κB, STAT, IRF, and MAPK signaling. For instance, while iron oxide and certain titanium nanoparticles (TNPs) typically promote M1 polarization, gold and silicon nanoparticles are often shown to induce an M2 phenotype. The effects of other metals, like copper and silver, are highly concentration-dependent or can be tailored through surface functionalization. This analysis underscores the potential of engineered metal nanoparticles to precisely direct macrophage polarization for therapeutic benefit, such as repolarizing tumor-associated macrophages for cancer immunotherapy or promoting M2-mediated tissue regeneration in wound healing. Understanding these intricate interactions is crucial for advancing the application of nanomedicine in immunotherapy and for assessing the safety profile of nanomaterials. 

Abstract Background: Melanoma is the most aggressive form of skin cancer and is associated with high mortality when not diagnosed at an early stage. Recent advances in dermatoscopic image analysis combined with artificial intelligence have demonstrated considerable potential for improving diagnostic accuracy. ConvMixer, a hybrid deep learning architecture that integrates convolutional neural networks with a mixer-style design, has recently emerged as a powerful model for image classification tasks. This study aimed to evaluate the effectiveness of the ConvMixer model for automated melanoma detection using dermatoscopic images. 
Methods: Dermatoscopic images were collected from two publicly available datasets: The International Skin Imaging Collaboration (ISIC) and the Public Health (PH2) database. The ISIC dataset comprised 31,696 benign lesions and 7,319 malignant melanoma images, which were divided into training (80%), validation (10%), and test (10%) sets. The PH2 dataset, consisting of 40 melanoma and 160 melanocytic nevi images, was used exclusively for external testing. Image preprocessing, normalization, and data augmentation were performed prior to model training. Model performance was assessed using sensitivity, specificity, accuracy, F1 score, and the area under the receiver operating characteristic curve (AUC).
Results: The ConvMixer model demonstrated strong discriminative ability between malignant and benign skin lesions across both datasets. On the ISIC dataset, the model achieved a sensitivity of 0.9126, specificity of 0.6683, and accuracy of 0.7142. On the PH2 dataset, higher specificity (0.95) and accuracy (0.905) were observed, along with a sensitivity of 0.725. High AUC values further confirmed robust classification performance and generalizability across datasets with differing characteristics.
Conclusion: The ConvMixer model shows strong potential as an effective AI-assisted tool for melanoma detection from dermatoscopic images. Its consistent performance on both large-scale and controlled datasets supports its applicability in diverse clinical settings, highlighting its value for early melanoma screening and decision support in dermatology.

Abstract Background: Three-dimensional (3D) printing application is a promising method for the development of cell-friendly bone substitutes with appropriate properties. In this study, we developed 3D polycaprolactone (PCL)-based scaffolds by 3D printing technology, and the osteogenic differentiation of pre-osteoblast MC3T3 cells on these scaffolds was evaluated. 
Methods: Considering that PCL is naturally hydrophobic and lacks active interaction sites, oxygen plasma surface modification was carried out to provide a suitable hydrophilic surface for PCL-simvastatin interaction. Different HA concentrations (0.5, 1, and 1.5 % w/v) were added to PCL scaffolds, and the scaffolds with 1% HA showed good printability with interconnected porosity.
Results: The mechanical properties exhibited an increase of 2.67 times in comparison to PCL scaffolds. The addition of HA and oxygen plasma treatment increased the hydrophilicity and swelling ratio, and the final PCL scaffolds with 1%HA and simvastatin (PHPB) showed the highest percentage of biodegradation with 36.65±3.75 (%) biodegradation ratio after 21 days. The biological studies indicated that surface modification of the PCL scaffolds provided a suitable hydrophilic platform for attachment, osteogenic differentiation, and proliferation of MC3T3 cells. 
Conclusion: It seems that PHPB scaffolds are promising for bone tissue regeneration applications.

Abstract Background: Critical-sized bone defects represent a major clinical challenge due to their limited capacity for spontaneous healing. Autologous bone grafting, while effective, is associated with donor-site morbidity and limited tissue availability. Tissue engineering approaches using osteoblasts combined with biocompatible scaffolds offer promising alternatives. We evaluated the effectiveness of homologous osteoblast transplantation on commercially available hydroxyapatite/beta-tricalcium phosphate (HA/β-TCP) scaffolds in promoting the repair of critical-sized tibial defects in a rabbit model.
Methods: Critical-sized defects (3 mm²) were surgically created in the tibia of 12 male New Zealand white rabbits. Animals were randomly assigned to receive either osteoblast-loaded HA/β-TCP scaffolds or acellular scaffolds. Contra-lateral limbs served as untreated controls. Bone regeneration was assessed 6 weeks post-implantation via histology, alkaline phosphatase (ALP) staining, and quantitative analysis of bone thickness and cellularity.
Results: Osteoblast-seeded scaffolds significantly improved bone healing compared to controls and acellular scaffold groups, demonstrated by increased new bone formation, enhanced tissue thickness, and higher osteoblast counts (P<0.05). Histological analyses revealed abundant collagen matrix and mineralized bone within the scaffold pores in the osteoblast group. 
Conclusion: Homologous osteoblast transplantation utilizing HA/β-TCP scaffolds significantly promotes bone regeneration in critical-sized tibial defects in rabbits, demonstrating superior efficacy compared to acellular scaffold treatment. This strategy represents a promising approach for advancing clinical bone repair therapies.