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 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. 

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: Given the challenges in isolating mesenchymal stem cells (MSCs) from bone marrow (BM), umbilical cord blood (UCB) can be a promising source of MSCs. On the other hand, cryopreservation of adherent MSCs is a solution for long-term storage of these cells and subsequent experimental use of them. In the present study, we investigated the isolation and identification of UCB-MSCs and the effect of cell freezing with dimethyl sulfoxide (DMSO).
Methods: The successfully isolated UCB-MSCs were cultured in DMEM containing 15% fetal bovine serum and 1% penicillin-streptomycin. After flow cytometric analysis of the cells, we investigated the differentiation potential of MSCs. Finally, the CFU-F assay was performed before and after freezing with 5% and 10% DMSO.
Results: Results showed that the average number of mononuclear cells obtained from 12 UCB samples was 58.2±10.7×106 with a viability rate of 90±3%. MSCs were successfully isolated with a 33% recovery rate. These cells had fibroblastic-like morphology and were immunophenotypic, with adipogenic, osteogenic, chondrogenic, and neural differentiation capacities.
Conclusion: Based on the results, the use of 5% DMSO for UCB-MSC cryopreservation is recommended as an alternative to the conventional 10% DMSO. The UCB should be considered a promising alternative to BM as a source of MSCs. The use of the slow-freezing method with two concentrations of DMSO is effective in retaining the proliferation, cell-surface markers, and differentiation ability of human UCB-MSCs.

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: Liver diseases are a major global cause of mortality and are in urgent need of innovative therapeutic strategies. This review explores the role of small molecules as key modulators in liver tissue regeneration.
Methods: A comprehensive review of the literature was conducted to evaluate the regenerative potential of small molecules and their underlying mechanisms in liver tissue engineering and regenerative medicine. Particular attention was given to molecules involved in regulating key signaling pathways associated with hepatocyte proliferation, fibrosis inhibition, differentiation, and cell survival.
Results: The findings indicated that compounds such as CHIR99021 (activator of the Wnt/β-catenin signaling pathway), SB431542 (inhibitor of the TGF-β pathway), dexamethasone (inducer of hepatocytic differentiation), and Y-27632 (enhancer of cell survival) can effectively promote hepatocyte proliferation, reduce fibrotic progression, and enhance hepatic functionality through distinct molecular mechanisms. The targeted application of these molecules—especially within engineered microenvironments such as 3D-bioprinted scaffolds or hydrogels—can further improve regenerative outcomes by mimicking native extracellular matrix conditions and supporting cell–matrix interactions.
Conclusion: Despite existing challenges such as safety concerns, the need for targeted delivery systems, and limited clinical evidence, integrating these agents with advanced technologies, including 3D bioprinting and personalized medicine, offers a promising outlook for the treatment of liver diseases. Future efforts should focus on optimizing combinatorial small-molecule therapies, developing smarter delivery platforms, and validating these approaches in clinically relevant models to accelerate translation into regenerative hepatology.

Abstract Exosomes are nanosized extracellular vesicles (EVs) (30–150 nm) secreted by virtually all cell types, acting as natural carriers of biomolecules, including proteins, lipids, and nucleic acids, to mediate intercellular communication. They participate in a wide range of physiological and pathological processes such as immune modulation, angiogenesis, tissue regeneration, tumor progression, infection propagation, and metabolic regulation. Their intrinsic biocompatibility, stability in biological fluids, and ability to cross biological barriers make them promising tools for diagnostics, targeted drug delivery, and regenerative medicine. The present study systematically reviews biological characteristics and functional roles of exosomes, emphasizing their dual behavior in health and disease. It further evaluates current and emerging methodologies for exosome isolation and purification, including conventional ultracentrifugation, size‑exclusion chromatography (SEC), filtration, precipitation, and immunoaffinity approaches, as well as advanced microfluidic and hybrid multimodal systems. Particular attention is given to new commercial and integrated platforms combining tangential flow filtration (TFF) and SEC modules for good manufacturing practice (GMP)–compatible exosome production. Despite considerable progress, challenges remain regarding heterogeneity, yield optimization, and preservation of biological activity. Understanding how isolation methods influence exosome quality and functionality is essential for their safe and standardized clinical translation. This review highlights the need for integrated, high‑purity, and reproducible workflows guided by the latest MISEV recommendations to unlock the full therapeutic and diagnostic potential of exosomes.

Abstract Background: Zinc-oxide (ZnO) nanoparticles (NPs) have wide industrial and biomedical applications. Determining the mechanisms of NPs action is challenging in clinical application particularly in future cancer therapy. However, the genetic and epigenetics effect of ZnO-NPs on autophagy (ATG) and apoptosis related long non-coding RNA (lncRNA) have not been studied.
Methods: ZnO-NPs were synthesized, characterized, and evaluated their effects on MCF-7 cells. In the following, breast cancer cells were treated with ZnO-NPs in the presence or absence of N-acetyl-L-cysteine (NAC, reactive oxygen species [ROS] inhibitor), 3-methyladenine (3-MA, ATG inhibitor), and Z-VAD-FMK (apoptosis inhibitor). Finally, genetic and epigenetic modification on ATG and apoptosis related lncRNA, such as DNA methylation, histones modification, and alteration in lncRNA expression were investigated.
Results: Comparison between non-exposed and exposed cells revealed a significant increase in GAS5 expression, whereas XIST, TUG1, and MALAT1 were significantly downregulated. Histone modification analysis demonstrated enrichment of H3K4me3 at the GAS5 promoter. In contrast, H3K27me3 levels were significantly increased at the promoters of XIST, TUG1, and MALAT1. Consistently, promoter methylation analysis showed decreased methylation in GAS5, while methylation levels were significantly increased in XIST, TUG1, and MALAT1.
Conclusion: It seems that lncRNA modulate the crosstalk between ATG and apoptosis via regulating the expression of related genes. The present study may provide new insights into the mechanism of NPs interference with ATG and apoptosis related lncRNA in cancer therapeutic.

Abstract Background: Bone regeneration remains a major challenge in regenerative medicine because successful repair requires the coordinated regulation of osteogenesis, angiogenesis, and immune responses within complex defect microenvironments. Extracellular vesicles (EVs), including exosomes and microvesicles, have emerged as promising acellular therapeutic agents capable of reproducing many of the regenerative effects of stem and progenitor cells while reducing the risks associated with cell-based therapies.
Methods: This narrative review synthesizes current evidence on the biological functions, cellular sources, engineering strategies, and therapeutic applications of EVs in bone regeneration. Relevant studies published between 2015 and 2025 were reviewed, focusing on molecular mechanisms, bioengineering approaches, disease-specific applications, and translational challenges associated with EV-based therapies.
Results: EVs derived from diverse sources, including bone marrow, adipose tissue, dental pulp, muscle cells, and gut microbiota, were shown to promote bone regeneration through the delivery of bioactive proteins, lipids, nucleic acids, and metabolites. These vesicles regulate key regenerative pathways, including PI3K/AKT, BMP/Smad/RUNX2, Wnt/β-catenin, TGF-β1/Smad/MAPK, and microRNA-mediated signaling. EVs enhance osteogenesis, stimulate angiogenic–osteogenic coupling, modulate macrophage polarization toward a reparative M2 phenotype, and improve bone healing under aging, diabetic, and osteoporotic conditions. Advanced bioengineering strategies, such as scaffold functionalization, hydrogels, nanoparticle conjugation, and genetic engineering, further improve EV targeting, retention, and controlled release. Preclinical studies demonstrate substantial regenerative benefits across a range of musculoskeletal disorders.
Conclusion: EV-based therapies represent a promising and versatile platform for bone regeneration by integrating osteogenic, angiogenic, and immunomodulatory functions within a cell-free therapeutic framework. Although significant challenges remain, including standardization of EV isolation, scalable manufacturing, potency assessment, and clinical reproducibility, ongoing advances in bioengineering and precision medicine may accelerate the translation of EV-based therapeutics into clinical practice for musculoskeletal repair.

Abstract Background: In this study, the physical properties of a calcium hydroxide/hydroxyapatite (CH/HA) cement were investigated as a novel bioactive material for the repair of bone and dental defects.
Methods: The powder phase, consisting of varying proportions of CH and HA, was mixed with glycol disalicylate as the liquid phase. The setting reaction produced an amorphous matrix containing dispersed HA particles adjacent to unreacted CH particles, as confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses. Elemental phosphorus mapping from X-ray analysis of SEM images further confirmed the presence and distribution of HA particles within the cement matrix.
Results: The cements exhibited setting times ranging from 2.9±0.5 to 7.8±0.8 min, depending on composition. Injectability increased from 68±3% to 86±6% as HA content increased, with no evidence of filter pressing or phase separation. After 24 h of setting, compressive strengths ranged from 55±2.6 to 62.3±2.8 MPa, which are higher than those typically reported for conventional calcium phosphate cements (CPCs). After 3 days of immersion in distilled water, the compressive strength decreased to 43.0–49.2 MPa due to partial matrix dissolution. The cements exhibited controlled calcium ion release over 28 days, with higher release observed in formulations containing greater amounts of CH. Furthermore, the pH of cement suspensions increased rapidly during the first 30 min and then stabilized in the alkaline range. Water solubility decreased from 6.85±0.12% to 2.95±0.12% with increasing hydroxyapatite content.
Conclusion: The developed CH/HA cement has promising mechanical and handling properties for potential biomedical applications in bone and dental tissue repair.

Abstract Background: Despite significant progress in calcium phosphate cement (CPC) development, conventional formulations still suffer from limitations that limit their clinical applicability.
Methods: In this study, novel injectable nanocomposite bone cements for bone and cranial defect reconstruction were developed by incorporating an equimolar mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) powders as the primary reactive phase into 3 wt/v% hyaluronic acid (HA) solutions with two different molecular weights (500 and 1750 kDa). The physical, physicochemical, and structural properties of the developed cements were evaluated and compared with those of conventional CPC, prepared using the same powder phase and distilled water as the liquid component.
Results: It was demonstrated that the prolonged setting time and low compressive strength of CPC can be significantly improved by incorporating HA in a molecular-weight-dependent manner. HA also acted as a viscosity-enhancing agent, showing a pronounced effect on cement injectability, particularly with high-molecular-weight HA. X-ray diffraction (XRD) analysis of the set cements revealed that, in both control and HA-containing formulations, the initial reactants were completely converted into nanostructured apatite after immersion in simulated body fluid. A slightly higher rate of apatite formation was observed in the HA 1750 kDa group compared to the other formulations. SEM observations confirmed a globular microstructure composed of tightly interconnected plate-like apatite nanocrystals in all samples.
Conclusion: The developed calcium phosphate–HA nanocomposite cements have strong potential to be used as injectable bone graft materials for bone defect repair following appropriate in vivo evaluations.

Abstract Background: Epidermolysis bullosa (EB) is a rare genetic disorder characterized by severe skin fragility, necessitating specialized wound care that reduces tissue damage during dressing changes. This study aimed to fabricate and characterize a novel, electrospun nanofibrous wound dressing designed specifically for EB management.
Methods: The composite scaffold—comprising polyvinyl alcohol, carboxymethyl cellulose, gelatin, and polycaprolactone—contained Moringa oleifera leaf extract (MOLE), as a bioactive agent, and nanostructured lipid carriers (NLCs) to reduce cell adhesion to the dressing.
Results: The NLC-loaded scaffold with MOLE had smooth, bead-free morphology with an average fiber diameter of 190.02 nm. The addition of NLCs resulted in appropriate surface wettability (contact angle=61.3°), maintained an ideal water vapor transmission rate of 8.55 mg/cm²h, and had suitable porosity (68.43%) and water uptake capacity (269%), ensuring a significant reduction in fibroblast adhesion, indicating the dressing’s potential for atraumatic, painless removal. Furthermore, MTT and live/dead assays confirmed the scaffold’s excellent biocompatibility, with high quantitative cell viability (91.9% and 87.8% on days 2 and 3, respectively) over 72 hours. Moreover, gene expression test showed a significant increase in expression of COL7A1 gene, confirming the scaffold’s potential to promote the structural regeneration of fragile skin.
Conclusion: The fabricated electrospun dressing that contained MOLE and NLCs has a great potential as a biocompatible dressing for the effective treatment and regeneration of fragile EB skin wounds.

Abstract Background: The development of a scaffold capable of providing a suitable environment for bone regeneration faces significant challenges. In addition to meeting the requirements related to material selection and fabrication techniques, a bone scaffold must ensure adequate porosity to facilitate osteogenesis and vascularization, while also maintaining sufficient mechanical strength during the early stages of bone healing and recovery.
Methods: A biodegradable cellulose-based hydrogel scaffold composed of hydroxyethyl cellulose (HEC), hydroxypropyl methylcellulose (HPMC), gelatin, and β-tricalcium phosphate (β-TCP) was developed for wound-healing applications using a freeze-drying technique. Different formulations of HEC/HPMC/gelatin/β-TCP scaffolds were initially prepared. To evaluate scaffold performance, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), mechanical testing, degradation analysis, swelling measurements, and antibacterial assays were performed.
Results: Among the prepared formulations, the HEC70–HPMC30 scaffold showed the most favorable mechanical properties, with a tensile strength of approximately 30 MPa, Young’s modulus of 1800 MPa, and elongation at break of ~2%. The scaffold also displayed a highly porous interconnected structure with an average pore size of nearly 100 μm. To improve structural stability, gelatin crosslinked with genipin was incorporated into the optimized polymer matrix, extending the degradation time from approximately 1 h to 24 h. Subsequently, β-TCP was added at concentrations of 10, 20, and 30 wt/v%. SEM observations revealed that increasing β-TCP content promoted a more organized pore architecture and more uniform pore distribution. FTIR and elemental mapping analyses confirmed the successful incorporation and homogeneous distribution of β-TCP within the scaffold network. The incorporation of β-TCP significantly affected the physicochemical properties of the scaffolds. Water uptake decreased from 712% in the control scaffold to 402% in the scaffold containing the highest β-TCP concentration after 9 h, while degradation after 24 h decreased to approximately 85%, indicating enhanced structural stability. However, no antibacterial activity was observed against Escherichia coli or Staphylococcus aureus.
Conclusion: The developed HEC/HPMC/gelatin/β-TCP scaffolds exhibit favorable mechanical performance, controlled degradation, and improved structural stability, demonstrating their potential as promising candidates for wound healing

Abstract Background: A bioorthogonally modified calcium phosphate cement (CPC) was developed to enhance hydroxyapatite (HA) formation, porosity, and biological performance for bone tissue engineering applications.
Methods: The modification strategy was based on surface functionalization of α-tricalcium phosphate (α-TCP) powders with azide- and cyclooctyne-containing molecules to promote apatite nucleation and bioactivity.
Results: Structural characterization by X-ray diffraction (XRD ) revealed enhanced HA formation in modified samples. The ratio of the HA peak to the α-TCP peak indicated accelerated HA formation. SEM observations revealed a transition from cauliflower-like and needle-like apatite morphologies in control samples (C-CPC) to plate-like HA morphologies in modified cements (M-CPC), resembling natural bone apatite. Porosity measurements showed a significant increase from nearly 43 for C-CPC to 71 for M-CPC. Despite the higher porosity, both groups exhibited similar biodegradation behavior over 28 days of immersion, with the pH decreasing only slightly from 7.2 to approximately 6.9. Mechanical evaluation indicated reduced compressive strength, Young’s modulus, and energy absorption in M-CPC, which was attributed to increased porosity and changes in apatite morphology. Cytocompatibility assessment demonstrated cell viabilities, exceeding 90% in most conditions and remaining above 85% in all cases, satisfying ISO 10993-5 requirements. SEM analysis further confirmed favorable cell attachment and spreading on both cement surfaces.
Conclusion: The findings demonstrate that bioorthogonal modification of CPCs effectively enhances apatite formation, porosity, and biological performance while maintaining acceptable biocompatibility.

Abstract Background: Chronic low‑grade inflammation plays a central role in the development and progression of type 2 diabetes mellitus (T2DM). MicroRNAs (miRNAs) have emerged as promising regulators of inflammatory pathways and potential non‑invasive biomarkers for early disease detection. This study aimed to investigate the expression levels of miR‑20a‑5p and miR‑149‑5p and their association with pro‑inflammatory cytokines in individuals with T2DM, pre‑diabetes, and non-diabetics.
Methods: A total of 90 participants were enrolled and divided into three groups: non-diabetic (n=30), pre‑diabetic (n=30), and T2DM (n=30), according to the American Diabetes Association (ADA)’s criteria. Serum levels of miR‑20a‑5p and miR‑149‑5p were quantified using real‑time polymerase chain reaction (PCR). The expression levels and protein concentrations of inflammatory cytokines (IL‑6, IL‑1β, TGF‑β, and IFN‑γ) were assessed by real‑time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic power of the selected miRNAs.
Results: The expression of miR‑20a‑5p was significantly upregulated in both pre‑diabetic and T2DM groups, whereas the expression of miR‑149‑5p was significantly downregulated in the T2DM group. ROC analysis revealed excellent diagnostic power of miR‑20a‑5p for distinguishing T2DM (AUC=0.985) and pre‑diabetics (AUC=0.895) from non-diabetic controls. Elevated expression and serum levels of IL‑6, IL‑1β, TGF‑β, and IFN‑γ were observed in pre‑diabetic and T2DM groups. miR‑20a‑5p showed a significant positive correlation with pro‑inflammatory cytokines (P<0.001). while miR‑149‑5p demonstrated a significant negative correlation (P<0.001).
Conclusion: The dysregulated expression of miR‑20a‑5p and miR‑149‑5p is closely associated with inflammatory responses in T2DM and pre‑diabetes. miR‑20a‑5p has higher diagnostic accuracy and may serve as a promising circulating biomarker for early detection of diabetes‑related metabolic and inflammatory alterations.

Abstract The scientific community was deeply saddened by the passing of Professor Reza Fekrazad on July 20, 2026. He was a distinguished clinician-scientist, an influential academic leader, and an esteemed member of the Editorial Board of the Journal of Translational and Regenerative Medicine. His untimely passing represents a profound loss to his family, friends, colleagues, and students, as well as to the international communities of photomedicine, laser dentistry, and regenerative science.