Search Results (154)

Hydrogel scaffolds have emerged as instructive microenvironments for craniofacial tissue regeneration, moving beyond passive cell carriers toward platforms that regulate cell fate, vascularization, immune remodeling, and tissue-specific architecture. This review synthesizes hydrogel-associated strategies across dental pulp, periodontal ligament, gingival, bone marrow, jawbone, endothelial, oral mucosal, induced pluripotent stem cell (iPSC), extracellular vesicle (EV), exosome, secretome, and acellular systems. The evidence indicates that craniofacial hydrogel performance is governed by reciprocal interactions among biological source, scaffold composition, matrix mechanics, spatial architecture, mineral or ionic signaling, growth factor delivery, vesicle-mediated communication, and inflammatory niche modulation. Mineralized and ion-releasing hydrogels most consistently supported osteogenesis and bone repair, whereas extracellular matrix (ECM)-mimetic, peptide, collagen, fibrin, gelatin methacryloyl (GelMA), alginate, hyaluronic acid (HA), and chitosan-based systems enabled pulp–dentin, periodontal, peri-implant, oral mucosal, and soft-tissue reconstruction. Responsive, antimicrobial, antioxidant, conductive, and immunomodulatory hydrogels further expanded the field by targeting diseased microenvironments rather than regeneration alone. Despite strong preclinical evidence, translation remains limited by heterogeneity in scaffold formulations, biological sources, analytical endpoints, defect models, and long-term functional validation. Future progress will require standardized characterization, tissue-specific design criteria, clinically relevant large-animal models, scalable cell-free technologies, and integrated assessment of regeneration, immunity, vascularization, innervation, mechanics, and safety. Full article

Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes involved in extracellular matrix remodelling in oral and dental tissues, including the periodontal ligament, alveolar bone, dentin, dental pulp, and periapical tissues. This narrative review summarises selected evidence on the role of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in orthodontic tooth movement, dental trauma and root resorption, restorative adhesive dentistry, and pulp/periapical disease. Particular attention is given to signalling pathways that regulate MMP/TIMP activity, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and transforming growth factor beta (TGF-β)/Smad-related mechanisms. The review also discusses the biomarker potential and translational status of MMP-targeted strategies. Across clinical contexts, MMP activity contributes to both matrix degradation and tissue repair, and its biological effect depends on local stimuli, TIMP-mediated regulation, pathway crosstalk, and the stage of disease or treatment. Full article

Coffee is among the most widely consumed beverages globally being cultivated in nearly 80 countries. Its processing generates large quantities of by-products, including mucilage, pulp/husks, silverskin, parchment, and spent coffee grounds. Although traditionally treated as waste, these residues are increasingly recognized as valuable resources rich in bioactive compounds exhibiting antioxidant, antimicrobial, and health-promoting properties. This review explores the antimicrobial potential of coffee by-products, with particular emphasis on their chemical composition and mechanisms of action. Compounds such as caffeine, chlorogenic acids, polyphenols, and melanoidins have demonstrated inhibitory effects against a broad spectrum of bacteria, including both Gram-positive and Gram-negative bacteria. Many of these compounds, which originate from plant’s defensive system or result from Maillard reactions, are known to disrupt microbial membranes, inhibit DNA repair, and interfere with pathogen metabolism. However, the available literature on their antimicrobial effectiveness remains limited. In the context of the rising worldwide concern over antimicrobial resistance, coffee by-products represent a sustainable and promising source of novel antimicrobial agents. Their valorization may support advances in food preservation, pharmaceutical innovation, and waste management practices, contributing to the implementation of a circular economy framework in the coffee industry while promoting environmental, economic, and social sustainability. Full article

Dental pulp tissue contains mesenchymal stem/progenitor cells that possess high proliferative potential for self-renewal. They are neural-crest derived cells and exhibit multi-lineage differentiation properties. These progenitor stem cells are now recognized as being vital to the dentin regeneration process following injury. Understanding the molecular mechanisms that mediate the differentiation of adult stem cells into odontoblasts and their use in the repair of the dentin–pulp complex is of significant interest in regenerative dental medicine. Dentin Phosphophoryn (DPP), synthesized and processed predominantly by the odontoblasts, functions both as a structural and signaling protein. We had previously demonstrated that DPP activates NF-κB and promotes Wnt5a expression in dental pulp stem cells. In this context, we observed that DPP can activate TAZ, a biologically potent transcriptional coactivator which serves as a downstream element of the NF-κB signaling cascade. Furthermore, binding of NF-κB p65 subunit to the TAZ promoter was facilitated by DPP stimulation, and their interaction was confirmed by ChIP analysis. In addition, DPP-dependent activation of the TAZ/TEAD reporter was confirmed by luciferase activity in DPSCs. Co-immunoprecipitation analysis confirmed the in vivo interaction between TAZ and β-catenin with DPP stimulation. This regulatory complex facilitated TAZ to bind to the conserved TEAD binding motifs of key gene targets involved in odontogenic differentiation such as RUNX2, OSX, OCN, ALP, BMP4, and WNT5A. Some of these genes also contain binding sites for the TCF/LEF transcription factors that interact with the Wnt effector, β-catenin. Activation of TAZ and β-catenin resulted in the upregulation of odontoblast gene expression and reduced expression in the presence of the TAZ–TEAD protein complex inhibitor. Using mandibles of DSPP KO and WT mice, we confirmed reduced TAZ and β-catenin protein levels in the dental pulp cells and in the odontoblasts of DSPP KO mice when compared with WT. Thus, DPP, an extracellular matrix protein, provides biological cues to activate the TAZ signaling pathway that can stimulate the terminal differentiation of DPSCs into functional odontoblasts. Full article

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers. Full article

The Wnt/β-catenin signaling pathway regulates key cellular processes, including proliferation, migration, differentiation, apoptosis and tissue homeostasis, and plays a pivotal role in tooth development and post-developmental dental physiology. In mineralized tissues such as bone and dentin, the Wnt signaling is critically involved in reparative and regenerative mechanisms. The Wnt signaling in the dentin–pulp complex is tightly controlled by extracellular modulators and receptor availability, and its balance appears crucial for an appropriate response. Hydraulic calcium silicate-based cements (HCSBCs) are widely used in endodontics due to their bioactivity and favorable biological properties. Increasing data indicate that HCSBCs promote odontogenic responses and reparative dentinogenesis through the recruitment and activation of dental stem cells (DSCs), possibly via the Wnt/β-catenin signaling pathway modulation. Therefore, the aim of the present narrative review was to summarize current knowledge on the role of the Wnt signaling in oral tissues and its interaction with HCSBCs. It is hypothesized that these materials may enhance pathway activation through the release of ionic products, growth factors and inflammatory mediators, thereby supporting biologically driven reparative processes. Understanding these mechanisms may guide the development of next-generation biomaterials designed to optimize the intrinsic regenerative potential of the dentin–pulp complex. Full article

Objective: To report a rare case of pulp space tissue growth in a mature mandibular molar with severe endo-periodontal involvement after conservative endodontic treatment and to discuss the possible biological explanations, including regeneration and granulation tissue healing. Severe endo-periodontal lesions are challenging, particularly as endodontic regeneration is usually observed in immature teeth, while revascularization in mature teeth, especially in cases of advanced periodontal disease, is rare, as demonstrated in this case. Methods: This study reports a rare case of tissue regeneration versus granulation tissue healing in the pulp space, occurring alongside periodontal healing, in a mature mandibular molar with necrotic pulp and severe periodontal involvement. A 52-year-old patient presented with a mature mandibular molar (tooth #19) exhibiting necrotic pulp with severe endo-periodontal involvement, including grade-3 mobility, tenderness to percussion, a 12 mm probing depth, and extensive periradicular radiolucency. The tooth was diagnosed with necrotic pulp and symptomatic apical periodontitis and was deemed hopeless, with extraction planned. Results: Following patient refusal, endodontic treatment was initiated, including cleaning, shaping, and placement of the intracanal medicament, Ledermix. The patient canceled the extraction due to symptom resolution and disappeared for 12 months. On return, the patient presented with spontaneous pain exacerbated by thermal stimuli, consistent with symptoms of irreversible pulpitis. Clinical examination revealed significant clinical and radiographic improvements, including reduced probing depth (3 mm), no mobility, resolution of apical translucency, radiographic findings suggestive of canal narrowing, and a positive pulp sensibility response. Re-entry elicited profuse bleeding with newly formed vital tissue beneath the medicament. Sodium hypochlorite irrigation failed to achieve hemostasis; inflamed tissue was removed; root canals were cleaned, shaped and obturated; and treatment was completed with placement of a permanent coronal resin composite restoration. A forty-month follow-up showed an asymptomatic tooth with clinical and radiographic healing. Conclusions: This case demonstrates that conservative endodontic management may result in favorable clinical and radiographic outcomes in mature teeth with severe endo-peroidontal involvement, influencing extraction decisions. It provides clinical evidence suggestive of tissue regeneration and periodontal healing in a mature tooth with necrotic pulp and severe periodontal compromise, challenging conventional prognosis. The observed pulp space tissue growth may be suggestive of regeneration; however, alternative explanations, including granulation tissue healing or repair processes, cannot be excluded. Healing by granulation tissue in the pulp space remains possible. Root canal treatment in advanced endo-perio lesions can yield favorable outcomes and may influence extraction decisions. Further clinical and histological studies are needed to clarify underlying mechanisms and optimize treatment strategies. Full article

Background/Objectives: The transformation of multifunctioning nanomaterials, incorporating antimicrobial activity and regenerative incompatibility, is becoming even more significant in the modern dental therapeutic context. Streptococcus mutans (S. mutans) is primarily linked to dental caries and pulp inflammation and requires new strategies that would be efficient at controlling the infection and promoting tissue repair. The objectives of the present research were to synthesize and critique the use of chitosan–eugenol carbon dots (CECDs) as a versatile nanoplatform in the field of dentistry to implement antimicrobial and regenerative dentistry. Methods: CECDs synthesized from biocompatible chitosan and eugenol were characterized by Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX), evaluated from S. mutans inhibition via MIC/MBC, and assessed from cytocompatibility using 3T3-L1 fibroblast viability, morphology, and migration assays. Results: The resultant CECDs had a spherical morphology and a size of 5 ± 2 nm. The EDX analysis established the existence of carbon, nitrogen and oxygen labeling successful incorporation of heteroatoms, as well as surface functionalization. CECDs exhibited greater antibacterial effects against S. mutans through a concentration-dependent approach with MIC and MBC of 125 and 250 µg/mL respectively. Cytotoxicity assays indicated that the cells were viable, their morphology was intact, and that the cells moved more vigorously, which confirmed excellent biocompatibility. Conclusions: The synergistic combination of chitosan and eugenol into the carbon dot structure produced CECDs that had strong biomarker along with antibacterial activity and desirable cytocompatibility. These results indicate that CECDs are an attractive multifunctional nanoplatform in the treatment of oral infections and help with wound healing. Full article

Autogenous grafts remain the gold standard for repairing extensive maxillofacial bone defects, but their associated morbidity motivates the search for alternative strategies in tissue bioengineering. Deciduous dental pulp stem cells (DDPSCs) represent a promising cell source due to their accessibility, multipotency, and osteogenic potential, while nanostructured carbonated hydroxyapatite (cHA) microspheres exhibit biochemical similarity to bone mineral and favorable bioabsorption. This study investigated the osteogenic response induced by the association of DDPSCs with cHA in a rat calvaria critical-size defect model. DDPSCs were expanded, seeded onto cHA microspheres, and characterized in vitro prior to bilateral implantation in 12 Wistar rats, with each animal receiving cHA + DDPSC on the right defect and acellular cHA on the left. After 60 and 90 days, histological and histomorphometric analyses revealed new bone formation in both groups, predominantly from the defect margins toward the center. At 60 days, no significant difference in newly formed bone was observed between groups (p = 0.249). At 90 days, the DDPSC + cHA group demonstrated significantly greater bone formation compared with acellular cHA (median 40.70 vs. 11.10 histomorphometric points; p = 0.028) and significant reduction in connective tissue (p = 0.028). Complete scaffold resorption was observed in all DDPSC-treated defects at 90 days, whereas residual biomaterial persisted in the cHA group (p = 0.015), indicating progressive cHA resorption over time. These findings suggest that combining DDPSCs with cHA enhances bone regeneration and that this synthetic, bioabsorbable scaffold represents a promising strategy for future applications in bone tissue engineering. Full article

Human skin lipids form interconnected pools that support barrier integrity, immune balance, and interactions with the environment. The stratum corneum barrier is built from an ordered mix of ceramides, cholesterol, and long-chain free fatty acids, while sebaceous lipids and their breakdown products shape surface properties and the skin microbiome. Hexadecenoic fatty acids are key at this interface. Palmitoleic acid (cis-9 16:1; 16:1 n−7, POA) is enriched in viable epidermis and remains detectable in stratum corneum lipids, whereas its isomer sapienic acid (cis-6 16:1; 16:1 n−10) predominates in human sebum. Together, they influence membrane organization, lipid fluidity, and antimicrobial defense. This mini-review outlines skin lipid composition and function with a focus on POA and then summarizes experimental and preclinical topical evidence suggesting antimicrobial effects, enhanced lubrication properties, protection from oxidative and ultraviolet B (UVB) injury, and enhanced wound repair. It also reviews early clinical findings from oral POA supplementation trials reporting improved hydration, barrier function, and markers of photo-oxidative aging, with exploratory signals for acne in a multi-nutrient regimen. Major POA sources include sea buckthorn pulp oil, macadamia and avocado oils, selected marine oils, ruminant fats, and emerging fermentation-derived products. Robust mechanistic human studies are still needed to define optimal dosing, formulations, and indications. Full article

Spi-C is a member of the ETS (E26 transformation-specific) family of transcription factors, a group of proteins that regulate gene expression in animals by binding to specific DNA sequences. Spi-C has emerged as a central regulator of macrophage adaptation to iron exposure, inflammatory stress, and tissue injury. Studies show that Spi-C programs iron-recycling macrophages by promoting expression of key iron-handling genes, thereby supporting iron efflux, safe intracellular iron storage, and the development of red pulp macrophages critical for systemic iron recycling. Its expression is strongly induced by heme and iron, enabling macrophages to respond adaptively to increased heme turnover, whereas Spi-C deficiency leads to impaired iron recycling and pathological iron accumulation. Beyond iron homeostasis, Spi-C is increasingly recognized as a regulator of inflammatory disease, functioning as an anti-inflammatory and tissue-protective factor across multiple models, including lipopolysaccharide (LPS)–induced systemic inflammation and colitis, where Spi-C deficiency leads to enhanced cytokine production, increased tissue injury, and impaired repair. By integrating NF-κB-driven inflammatory cues with metabolic adaptation, Spi-C maintains macrophage homeostasis across tissues. This short review summarizes these known functions and provides a forward-looking perspective that Spi-C may also regulate macrophage susceptibility to ferroptosis, an iron-dependent form of cell death implicated in diverse inflammatory and degenerative conditions. Full article

Extracellular vesicle (EV)-based therapies have emerged as promising, cell-free approaches for dental tissue regeneration. This narrative review integrates mechanistic insights, therapeutic efficacy data, and safety and delivery considerations from in vitro and in vivo studies to elucidate the molecular mechanisms by which EVs, particularly those from dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs), drive regenerative processes via key signalling axes (PI3K/Akt, MAPK, BMP/Smad, and Hedgehog). Preclinical studies demonstrate that unmodified and engineered EVs enhance odontogenic differentiation, angiogenesis, bone repair, and immunomodulation in models of pulp regeneration, alveolar bone defects, osteonecrosis, and periodontitis. Isolation and purification methodologies were also evaluated, comparing ultracentrifugation, size-exclusion chromatography, and density-cushion approaches, and discussing how protocol variations affect EV purity, dosing metrics, and functional reproducibility. Early-phase clinical evaluations report only low-grade transient adverse events, underscoring a generally favourable safety profile. Despite these encouraging results, significant challenges remain: heterogeneity in EV cargo composition, lack of standardised potency assays, and incomplete long-term safety data. The review highlights the urgent need for rigorous, harmonised regulatory frameworks and robust quality control measures to ensure that EV-based modalities can be translated into safe, effective, and reproducible therapies in regenerative dentistry. Full article

Background: Autologous platelet concentrates, including platelet-rich fibrin (PRF) matrices, have been proposed as biologically active scaffolds for vital pulp therapy. Evidence on the clinical use of different solid PRF matrices for direct pulp capping remains limited. Objective: The aim of this study is to describe and monitor two clinical cases of reversible pulpitis treated with direct pulp capping using two PRF membranes prepared by different centrifugation approaches, namely advanced platelet-rich fibrin plus (A-PRF+) and horizontal platelet-rich fibrin plus (H-PRF). Methods: In Case 1, A-PRF+ was prepared using a fixed-angle centrifugation protocol; in Case 2, H-PRF was prepared using a horizontal centrifugation protocol. In both cases, deep carious lesions with small carious pulp exposures (<1.5 mm) were managed by caries removal, ozone-assisted dentin disinfection, and direct pulp capping with the respective PRF membrane, followed by temporary calcium-silicate cement definitive coronal restoration. Clinical and radiographic follow-up, including cone-beam computed tomography, was performed for up to 12 months. Results: In Case 1 (A-PRF+), reparative dentin bridge formation was confirmed at 90 days, with a thickness of 0.2 mm. In Case 2 (H-PRF), reparative dentin was observed within 46 days, with a thickness of 0.28 mm. In both cases, pulp vitality was maintained, and no clinical symptoms or periapical changes were detected during the 12-month follow-up. Conclusions: These two cases suggest that direct pulp capping using PRF membranes (A-PRF+ or H-PRF), combined with ozone-assisted dentin disinfection and adequate coronal sealing, may be associated with maintained pulp vitality and hard-tissue repair after carious pulp exposure diagnosed as reversible pulpitis. Due to the descriptive two-case design and major confounding factors (including age and lesion characteristics), no comparative conclusions can be drawn. Prospective controlled clinical studies with standardized protocols are warranted. Full article

The intra- and intercellular signaling molecule nitric oxide (NO) is produced in endothelial cells by the activity of endothelial NO synthase (eNOS). Upon formation, NO diffuses into the underlying vascular smooth muscle cells, where it activates NO-sensitive guanylyl cyclase (NO-GC) resulting in the production of cyclic guanosine 3′,5′-monophosphate (cGMP) from guanosine 5′-triphosphate (GTP). Inducing vasodilatation, inhibiting platelet aggregation and leukocyte adhesion, and inhibiting the proliferation and migration of vascular smooth muscle cells, the NO-cGMP signaling leads to a number of anti-inflammatory processes. Inflammation-dependent elevated concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in blood vessels of inflamed dental pulp induce an uncoupling of eNOS and oxidized NO-GC, leading to a disruption of NO-cGMP signaling. Endothelial dysfunction in inflamed dental pulp alters cell–cell and cell–matrix interactions, reducing the regenerative and reparative potential of the dentin–pulp complex in response to carious lesions. In the therapeutic management of caries, it is essential to consider the presence of endothelial dysfunction in the inflamed dental pulp. The utilization of NO-GC stimulators and activators in indirect and direct pulp capping materials may enhance the regeneration and repair potential of inflamed dental pulp. Full article

Objectives: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body’s natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. Methods: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0–5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. Results: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. Conclusions: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine. Full article