Search Results (1,691)

Background: The periosteum and periosteum-derived cells have attracted considerable attention for their potential use in clinical applications for treating bone defects. Bovine periosteum-derived cells have been investigated because of their capability for scaffold-free bone regeneration. Previous mass spectrometry (MS) and immunohistochemistry studies have shown the presence of F-box/leucine-rich repeat protein 14 (FBXL14) in bovine periosteum and periosteum-derived cells. Recently, studies using ESI-Q-Orbitrap MS suggested the presence of type IV collagen in the periosteum. The aim of the present study was to clarify the relationship between type IV collagen and FBXL14 in the formation of periosteum-derived cells. Methods: Bovine periosteum-derived cells were obtained from Japanese Black Cattle’s legs in Medium 199 with ascorbic acid and 10% fetal bovine serum. Immunohistochemistry for type IV collagen and FBXL14 was performed using bovine bone with periosteum and periosteum alone for explant culture. Results: Both type IV collagen and FBXL14 were expressed in Volkmann’s canals and the Haversian canals in bone and periosteum. After 5 weeks, type IV collagen and FBXL14 surrounded crystals containing osteocalcin and had formed periosteum-derived cells. Von Kossa staining and immunostaining of osteocalcin revealed that the crystals contained calcified substances and osteocalcin. Conclusions: Clinically, understanding osteocalcin-interacting proteins will help promote bone regeneration. Interactions between type IV collagen and FBXL14 may contribute to scaffold-free bone regeneration. Full article

Background and Objectives: Adequate buccal bone thickness is critical for long-term peri-implant health and stability. When residual alveolar bone volume is insufficient, guided bone regeneration (GBR) is a widely adopted technique. While non-resorbable membranes provide structural support, they carry a higher risk of complications and require secondary surgery. Resorbable collagen membranes, offer promising biological properties and easier clinical handling, yet clinical data remain limited. This prospective cohort study aimed to evaluate the clinical and radiographic outcomes of horizontal GBR using a native, non–cross-linked resorbable porcine pericardium membrane fixed with titanium pins, in conjunction with simultaneous implant placement. Materials and Methods: Eighteen patients (26 implants) with horizontal alveolar defects (<6 mm) underwent implant placement and GBR with deproteinized bovine bone mineral and a porcine pericardium collagen membrane. Horizontal bone gain and buccal bone thickness were measured at baseline and 6 months post-operatively. Post-operative complications, patient-reported outcomes (PROMs), and peri-implant tissue health were assessed up to 1 year post-loading. Results: Mean bone gain was 2.95 ± 0.95 mm, and all sites achieved a buccal bone thickness ≥ 1.5 mm. No membrane-related complications occurred. PROMs revealed low morbidity. At 1-year follow-up, marginal bone loss averaged 0.54 ± 0.7 mm, mean probing depth was 2.79 ± 0.78 mm, 92% of sites exhibited keratinized mucosa ≥ 2 mm. Conclusions: Native resorbable porcine pericardium membranes, when combined with DBBM and mechanical stabilization, seem to be effective for horizontal bone regeneration. Full article

Background: Dental implants are widely used to replace missing teeth, particularly in aesthetically sensitive areas. The implant’s macrogeometry is crucial for ensuring primary stability and successful osseointegration. Internal conical connections and reactive surfaces on implants have shown positive outcomes in tissue and bone stability. In response, a hybrid conical dental implant was designed to address a variety of clinical scenarios. Materials and Methods: This pilot study evaluated the performance of the hybrid conical implant using histological and micro-CT analysis in a preclinical model with immediate loading. Five implants were placed in a mongrel dog, and histomorphometric and micro-CT assessments were performed after 60 days of healing. Results: Analysis showed a high degree of osseointegration, with BIC at 61.56% and BT/TV at 77%. Micro-CT confirmed these findings, with nBIC at 82.20%. Vertical measurements indicated stable crestal bone. Peri-implant tissue displayed organized supracrestal connective tissue, without signs of inflammation or bone saucerization. Polarized light microscopy revealed collagen fibers in perpendicular and oblique orientations around the abutment, suggesting mechanical integration and biological sealing despite the absence of a prosthetic crown. Conclusions: Within the limitations of this exploratory study with one animal study, the hybrid conical implant showed favorable biological and structural responses under immediate loading. These preliminary findings provide useful insights for the refinement of implant design, although further investigations in larger preclinical and clinical studies are required before clinical applicability can be confirmed. Full article

Meniscal injuries are common and often lead to chronic pain, joint instability, and an increased risk of osteoarthritis. Traditional treatments, such as partial meniscectomy, may accelerate joint degeneration. In recent years, biologically active therapies, including platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), hyaluronic acid (HA), bone marrow aspirate concentrate (BMAC), collagen, growth factors (GFs), and silk fibroin (SF), have emerged as promising strategies to enhance meniscal healing. This review evaluates the efficiency of these biological agents in promoting meniscal repair, with a particular focus on their potential integration into injectable hydrogel systems for targeted, minimally invasive delivery. Recent literature from 2015 to 2025 has provided growing insights into the role of biologically active agents and biomaterials in meniscal repair. Among the agents studied, PRP, MSCs, and HA have shown particular promise in modulating inflammation and supporting tissue regeneration. While biological therapies alone may not replace surgery for complex tears, they offer promising, less invasive alternatives that support tissue preservation. However, variability in study design, agent quality, and treatment protocols remains challenging. Further long-term research will be essential to confirm clinical benefits and optimize hydrogel-based delivery methods. Full article

Bone regeneration depends on a delicate balance between osteoblast-driven bone formation and osteoclast-mediated resorption, coordinated by complex biochemical cues. Magnesium (Mg²⁺) is known to modulate these processes. However, despite extensive research, its ability to simultaneously enhance osteogenesis and inhibit osteoclast activity remains unclear. In this study, we first investigated the effect of extracellular Mg²⁺ (0, 5, 10, 25, 50 mM) on osteoblast and osteoclast differentiation in 2D culture to determine whether a single Mg²⁺ dosing regimen can simultaneously promote osteogenesis while inhibiting osteoclast differentiation and maturation. A concentration dependent effect of Mg²⁺ was observed on both cell types, with increasing Mg²⁺ concentrations up to 25 mM significantly reducing osteoclast formation yet concurrently inhibiting osteogenic differentiation. At 50 mM, Mg²⁺ exhibited cytotoxic effects on both cell types. We then leveraged the osteogenic properties of biomimetic collagen/nano-hydroxyapatite (Coll/nHA) scaffolds by incorporating Mg²⁺ into the nHA phase to enable localised, controlled delivery. At a scaffold-loaded equivalent of 25 mM Mg²⁺, we observed enhanced bone matrix deposition alongside reduced osteoclast maturation, indicating a synergistic effect between Mg²⁺ and nHA in promoting osteogenesis. While no optimal synergistic dose was identified in 2D culture, these findings demonstrate that Coll-nHA scaffolds offer a promising strategy for localised Mg²⁺ delivery to enhance osteogenesis and suppress osteoclastogenesis. Importantly, the ease of scaffold modification opens the door to incorporating additional bioactive molecules, further advancing their potential in bone tissue engineering applications and the development of next-generation biomaterials for bone regeneration. Full article

Background/Objectives: With the aging of the population, the number of patients with osteoporosis is increasing worldwide. Osteoporosis results from an imbalance in bone remodeling by osteoblasts and osteoclasts. This study investigated the effects of sake lees and rice koji, traditional Japanese rice-fermented products, on bone metabolism. Methods: Both sake lees extract and rice koji extract increased alkaline phosphatase (ALP) activity, extracellular collagen accumulation, and mineralization of MC3T3-E1 cells. In addition, the intracellular protein levels of Hsp47 and Sec23IP, which are required for collagen maturation and secretion, respectively, were increased during the differentiation. On the other hand, both extracts significantly inhibited osteoclastic differentiation. Furthermore, the effects of freeze-dried sake lees or rice koji extract on osteoporotic bones were examined using twelve-week-old female C3H/HeJ ovariectomized (OVX) mice. Results: The groups of mice fed 20% or 40% freeze-dried sake lees showed significant suppression of the loss in bone volume fraction (BV/TV) and trabecular volume (Tb.V) compared with those fed a normal diet as well as the 40% freeze-dried sake lees-fed group reduced in the loss of trabecular thickness (Tb.Th). Similarly, the rice koji extract-treated mice showed significant inhibition of the loss in BV/TV, Tb.V, and even trabecular number (Tb.N.). Folic acid and S-adenosylmethionine (SAM), which have been reported to be present in sake lees, promoted extracellular collagen production by osteoblasts. Conclusions: In OVX mice, the intake of freeze-dried sake lees or rice koji extract was associated with the attenuation of trabecular bone loss, suggesting potential beneficial effects on bone metabolism. Full article

Background: Type I collagen is the most abundant protein of the extracellular matrix. Pathogenic variants in COL1A1 or COL1A2 are classically associated with osteogenesis imperfecta (OI) and Ehlers–Danlos syndrome (EDS). An emerging clinical entity—COL1-related overlap disorder—encompasses individuals exhibiting phenotypic features of both conditions. Methods: We report a 55-year-old male presenting with disproportionate short stature, grayish-blue sclerae, multiple fractures, long bone deformities, joint hypermobility, and atrophic surgical scarring. The patient also had long-standing, untreated childhood-onset hypopituitarism. Imaging studies revealed numerous prior fractures, bowing of forearm bones, and multiple Wormian bones. Results: Genetic testing confirmed a novel heterozygous COL1A1 exon 14 variant (c.940G > A, p.Gly314Arg), presenting with a phenotype consistent with a COL1-related overlap syndrome. Conclusions: This case expands the phenotypic spectrum of COL1A1 mutations and supports the concept of COL1-related phenotypic overlap. Full article

Hydrogels have emerged as promising biomaterials for oral tissue regeneration thanks to their high-water content, excellent biocompatibility, and ability to mimic native tissue environments. These versatile materials can be tailored to support cell adhesion, proliferation, and differentiation, making them suitable for repairing both soft and hard oral tissues. When engineered from natural polymers and enriched with bioactive agents, hydrogels offer enhanced regenerative potential. Biopolymer-based hydrogels, derived from materials such as chitosan, alginate, collagen, hyaluronic acid, and gelatin, are particularly attractive due to their biodegradability, bioactivity, and structural similarity to the extracellular matrix, creating an optimal microenvironment for cell growth and tissue remodeling. Recent innovations have transformed these systems into multifunctional platforms capable of supporting targeted regeneration of periodontal tissues, alveolar bone, oral mucosa, dental pulp, and dentin. Integration of bioactive molecules, particularly essential oils, bio-derived constituents, cells, or growth factors, has introduced intrinsic antimicrobial, anti-inflammatory, and antioxidant functionalities, addressing the dual challenge of promoting tissue regeneration while at the same time attenuating microbial contamination in the oral environment. This review explores the design strategies, material selection, functional properties, and biomedical applications in periodontal therapy, guided tissue regeneration, and implant integration of natural polymer-based hydrogels enriched with bioactive factors, highlighting their role in promoting oral tissue regeneration. In addition, we discuss current challenges related to mechanical stability, degradation rates, and clinical translation, while highlighting future directions for optimizing these next-generation bioactive hydrogel systems in regenerative dentistry. Full article

Background/Objectives: Vertical ridge augmentation remains a challenging procedure in alveolar bone reconstruction, with existing techniques often limited by surgical complexity, graft instability, and high resorption rates. This study evaluates the clinical and histological outcomes of a novel vertical ridge augmentation technique using a wide-head tenting pole screw (WHTPS) combined with sticky bone graft material. Methods: Five patients with vertical bone deficiencies (6–10 mm) in the maxilla or mandible underwent augmentation using a single WHTPS (rectangular or round wide-head type). Sticky bone was prepared using autologous tooth bone, allografts, or xenografts, combined with fibrin glue and covered with concentrated growth factor (CGF) membranes and/or resorbable collagen membranes. After 5–6 months of healing, the WHTPS was removed, and bone biopsies were taken for histological analysis. Results: Radiographic and histological evaluations confirmed successful ridge augmentation in all cases. Newly formed bone ranged from 21.2% to 57.5%. All patients proceeded to implant placement without complications. Radiographic, clinical, and histological assessments consistently showed that new bone formation extended up to the level of the screw head, indicating complete vertical fill of the augmented space. Histology showed well-integrated, mineralized bone with no signs of inflammation. The wide-head tenting pole screw was observed to support stable space maintenance and facilitate surgical handling and favorable outcomes in vertical ridge augmentation. Conclusions: In this case series, a single wide-head tenting pole screw appeared sufficient to maintain space and resist soft tissue pressure in wide alveolar bone defects during healing. This case series suggests that the wide-head tenting pole screw technique may be a feasible option for managing severe alveolar bone deficiencies. Full article

Background/Objectives: Osteoarthritis (OA) is a progressive joint disease characterized by inflammation, cartilage degradation, and subchondral bone changes, for which effective disease-modifying therapies are lacking. Messenger RNA (mRNA)-based therapeutics offer a versatile approach to modulate joint pathology, but their application to OA remains limited. Methods: We evaluated intra-articular delivery of therapeutic mRNAs using polyplex nanomicelles, a non-inflammatory and minimally invasive carrier system, in a rat model of inflammation-driven OA induced by monosodium iodoacetate (MIA). Results: IL-1 receptor antagonist (IL-1Ra) mRNA reduced synovial inflammation and alleviated pain and swelling. RUNX1 mRNA, a transcription factor critical for chondrogenesis, supported chondrocyte viability, type II collagen expression, and cartilage structure. Under conditions of pronounced inflammation, however, the protective effects of RUNX1 mRNA alone were modest. Notably, combined administration of IL-1Ra and RUNX1 mRNAs produced synergistic therapeutic benefits, with enhanced chondroprotection and preservation of subchondral bone integrity. Conclusions: These findings suggest that while RUNX1 is essential for maintaining cartilage homeostasis, effective control of joint inflammation is required for its therapeutic activity. Dual mRNA therapy delivered by polyplex nanomicelles therefore represents a promising strategy to address the multifactorial pathology of OA. Full article

Collagen, which has osteoconductive potential, has been widely used as a scaffold material for bone repair and regeneration for more than the last three decades. Recently, collagen has been combined with other materials to produce collagen-based bone grafting materials with enhanced bone repair and regeneration capacities. However, varied results have been obtained with collagen-based grafting materials. Methods: To elucidate the mechanisms underlying the enhanced bone engineering capacity of these materials, we critically reviewed the current literature on the complex hierarchical structure and properties of native collagen molecules. Results: This review highlights the scientific challenge of manufacturing collagen-based materials with suitable properties and shapes for specific biomedical applications, particularly those related to bone repair and regeneration. Conclusions: This article sheds light on the interactions between collagen and cell receptor molecules to mediate biological pathways. In addition, this article clarifies the mechanisms of cell adhesion-mediated bone regeneration. The findings may guide future research on collagen-based biomaterials. Full article

Zanthoxyli Pericarpium (ZP), the dried pericarp of mature fruits of Zanthoxylum schinifolium Siebold and Zucc., has traditionally been used in East Asian medicine for its medicinal properties, but its therapeutic potential in periodontitis has not been elucidated. In the present study, we investigated the effects of ZP on ligature-induced experimental periodontitis (EPD) in male Sprague Dawley rats. Animals were assigned to vehicle control, ligature control, ZP-treated (25, 50, and 100 mg/kg), or indomethacin-treated (5 mg/kg) groups (n = 10 per group) and orally administered the respective treatments daily for 10 days after ligature placement. ZP significantly reduced anaerobic bacterial proliferation and inflammatory cell infiltration in gingival tissue. ZP suppressed the production of inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, in both gingival tissues and lipopolysaccharide-stimulated RAW 264.7 macrophages, through inhibition of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. In addition, ZP decreased myeloperoxidase activity and reduced matrix metalloproteinase-8 expression, thereby preserving collagen areas. ZP also restored the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) balance, leading to a reduction in osteoclast numbers and their occupancy on the alveolar surface, and it effectively ameliorated horizontal alveolar bone loss. Furthermore, ZP exhibited antioxidant effects by lowering malondialdehyde levels and inducible nitric oxide synthase activity in gingival tissues. Statistical analysis was performed using ANOVA followed by a post hoc test, with significance set at p < 0.05. These findings indicate that ZP mitigates periodontitis through combined antimicrobial, anti-inflammatory, antioxidant, and anti-resorptive actions, supporting its potential as a therapeutic candidate for periodontitis. Full article

Extracellular matrix proteins have a complex assembly in tissue and it is believed that not only the chemical structure, but also their location, plays an important role in cellular functions. Collagen is one of the main components of the extracellular matrix and the oriented arrangement of collagen fibrils in tissues such as bone, cartilage, tendons, and cornea has a significant impact on various tissue functions. In the body, the orientation of extracellular matrix proteins is determined by cells. Oriented collagen fibrils can not only promote directed cell migration, but also stimulate cells to secrete an extracellular matrix with an oriented structure. However, the creation of collagen fibrils with an oriented structure in vitro is still associated with a number of limitations. Such limitations are primarily because the mechanisms regulating cellular functions in the orientation of extracellular matrix proteins, including collagen, are still unknown. Currently, only physical ways of organizing collagen fibrils in a certain direction are known. We hope that the description of the orientation of collagen fibrils in this review will allow readers to better understand the processes that occur with molecules. The study of methods and conditions for obtaining oriented collagen fibrils can help to obtain tissue biomimetic materials with complex properties identical to native tissues. Therefore, we discuss here various methods and conditions for obtaining oriented collagen fibrils in vitro using mechanical, electric, magnetic, and other fields. The prospects of application in tissue engineering and scientific problems of oriented collagen fibrils are also described. Full article

Background/Objectives: Anterior open bite is a multifact orial malocclusion influenced by genetic and environmental factors. Variants in the Collagen type I, alpha 1 (COL1A1) gene, particularly rs1800012, have been implicated in bone quality, but their role in craniofacial anomalies remains unclear. Methods: A case–control study was conducted with 60 participants (30 anterior open bite cases; 30 matched controls). DNA was extracted from buccal swabs, and rs1800012 genotyping was performed using TaqMan assays. Genotype and allele distributions were compared with chi-square and Fisher’s exact tests; Hardy–Weinberg equilibrium was assessed in controls. Results: Genotype (GG/GT/TT: 53.3/40.0/6.7% vs. 60.0/33.3/6.7%) and allele (T allele: 26.7% vs. 23.3%) frequencies did not differ significantly between cases and controls. No association was detected under additive, dominant, or recessive models (all p > 0.05). Wide confidence intervals indicated limited precision of effect estimates. Conclusions: This study provides no evidence of association between COL1A1 rs1800012 and anterior open bite in this Turkish cohort. The relatively small sample size, the rarity of the TT genotype, and the multifactorial nature of craniofacial development represent important limitations. Larger, multi-gene, and functionally integrated studies are required to clarify the genetic architecture of open bite malocclusion. Full article

Background and Objectives: In vitro evaluation of macro and microscopic features of five resorbable barrier membranes used for Guided Bone Regeneration (GBR) in oral hard tissue surgery. Materials and Methods: Five different resorbable barrier membranes were analyzed by optical microscopy and scanning electron microscopy (SEM). For each sample, surface appearance, the presence and size of ridges and depressions, number of layers, and the inner structure were recorded. Each membrane was cut into 1 × 1 cm squares to determine mass, density and thickness. In addition, an EDX microanalysis was performed. Results: Under optical microscopy, all membranes appeared rough, with ridges and depressions. In cross-section, only Sample 2 presented true stratification. On SEM, most membranes showed a three-dimensional collagen fiber architecture. Sample 3, a sheet of collagenated equine bone, differed accordingly. EDX spectra showed broadly overlapping elemental composition, characterized by N, O and C. The mass depends on the composition: bone-containing membranes weighed more; those composed predominantly of collagen weighed less. Conclusions: Pore size, surface density and roughness, and the type of cross-linking can influence cell interaction and may lead to different regenerative scenarios, potentially improving the quality and timing of tissue regeneration. Membrane selection should be dictated by the clinical scenario, prioritizing properties most advantageous for the defect. Full article