Search Results (586)

Platelet-rich plasma (PRP) is an autologous blood-derived concentrate increasingly utilized in regenerative medicine for its ability to accelerate healing and tissue repair. PRP is broadly classified by leukocyte content, fibrin architecture, and platelet concentration, with classification systems developed to standardize characterization. Preparation methods, including single- or double-spin centrifugation and buffy coat techniques, influence the final composition of PRP, determining the relative proportions of platelets, leukocytes, plasma proteins, and extracellular vesicles. These components act synergistically, with platelets releasing growth factors (e.g., VEGF, PDGF, TGF-β) that stimulate angiogenesis and matrix synthesis, leukocytes providing immunomodulation, plasma proteins facilitating scaffolding, and exosomes regulating intercellular signaling. Mechanistically, PRP enhances tissue repair through four key pathways: platelet adhesion molecules promote hemostasis and cell recruitment; immunomodulation reduces pro-inflammatory cytokines and favors M2 macrophage polarization; angiogenesis supports vascular remodeling and nutrient delivery; and serotonin-mediated pathways contribute to analgesia. These processes establish a regenerative microenvironment that supports both structural repair and functional recovery. Clinically, PRP has been applied across multiple specialties. In orthopedics, it promotes tendon, cartilage, and bone healing in conditions such as tendinopathy and osteoarthritis. In dermatology, PRP enhances skin rejuvenation, scar remodeling, and hair restoration. Gynecology has adopted PRP for ovarian rejuvenation, endometrial repair, and vulvovaginal atrophy. In dentistry and oral surgery, PRP accelerates wound closure and osseointegration, while chronic wound care benefits from its angiogenic and anti-inflammatory effects. PRP has also favored gingival recession coverage, regeneration of intrabony periodontal defects, and sinus grafting. Although preparation heterogeneity remains a challenge, PRP offers a versatile, biologically active therapy with expanding clinical utility. Full article

Introduction: Odontogenic keratocyst (OKC) is a locally aggressive cystic lesion derived from remnants of the dental lamina. It is most commonly located in the posterior mandible, while maxillary involvement is rare and poses diagnostic and surgical challenges due to its proximity to critical anatomical structures. This case report describes the surgical management of a maxillary OKC with an uncommon localisation. Methods: A 50-year-old male presented with an asymptomatic swelling in the posterior maxilla. Cone beam computed tomography (CBCT) revealed a well-defined unilocular radiolucency extending toward the maxillary sinus floor. Surgical management included complete enucleation and peripheral curettage, followed by histopathological confirmation. The defect was left to heal naturally through bone regeneration without the need for grafting. Results: Intraoperatively, a thin pearly white cystic capsule and buccal cortical thinning were observed, consistent with OKC. The lesion was enucleated intact, without rupture or sinus perforation. Histology confirmed the diagnosis. Postoperative healing was uneventful, with radiographic follow-up at one month showing favourable healing changes. Conclusions: Careful surgical planning combined with advanced imaging facilitates safe and effective management of OKCs in uncommon maxillary sites. Enucleation with peripheral curettage provided satisfactory short-term outcomes. Long-term follow-up remains essential due to the risk of recurrence. Full article

Background/Objectives: The use of dentin grafts in bone regeneration has gained increasing attention as an alternative to conventional grafting materials. Mesenchymal stem cells (MSCs), known for their osteogenic potential, have been combined with various biomaterials to enhance regenerative outcomes. This study aimed to evaluate the regenerative potential of dentin grafts and bovine-derived xenografts, with or without MSCs, in experimentally created bone defects in a rat model. Methods: A total of 25 male rats were randomly assigned to five groups: control, dentin graft, dentin graft and MSC, xenograft, and xenograft and MSC. Standardized 2-mm cortical defects were created bilaterally in the femoral shafts. Histological and immunohistochemical analyses were performed after a 90-day healing period. Statistical evaluation was carried out using the Kruskal–Wallis H test and Bonferroni-adjusted pairwise comparisons. Results: Complete healing was achieved in all groups without evidence of complications or inflammatory reactions. Immunohistochemical staining demonstrated no positive vascular endothelial growth factor (VEGF), collagen type I (COL1), or osteopontin (OPN) reactions in defect areas, consistent with complete maturation, although collagen type 3 (COL3) positivity was observed in residual xenograft material. Quantitative analysis showed that the dentin graft and MSC group achieved the highest degree of new bone formation (M = 92.88%, SD = 6.09), significantly greater than the control (p = 0.002) and xenograft groups (p = 0.013). Conclusions: Both dentin grafts and xenografts demonstrated enhanced bone defect healing when combined with MSCs. Nevertheless, dentin grafts in conjunction with MSCs yielded the most favorable regenerative outcomes, suggesting their clinical superiority over conventional xenografts. Full article

Xenograft bone, autologous bone grafts or allogeneic bones from a bone bank are used for bone augmentation, reconstruction or other purposes, when the volume, shape, and size of each jawbone defect require different bone materials. In the case of some bigger and locally advanced bone defects, the use of allogeneic bone can be suitable and used with great success if the wound and bone are especially carefully maintained; however, the healing period of each bone depends on good and stable wound closure followed by improved local antiseptic protocol. The individuality of each bone defect might also require additional prophylactic titanium plating in order to decrease the risk of possible mandibular fracture or to help improve bone stability, reduce bone mobility and possible inflammation or granulation tissue formation. Early radiological estimation of bone healing evaluation might be troublesome and not fully visible in radiological evaluation in the early stages of bone healing. On the other hand, possible bone inflammation, radiolucent defects, and granulation formation could be noted in cases of acute or long-lasting bone grafting material inflammation, bacterial contamination within the bone defect area, or the presence of fistula. The presented case describes a very good outcome from a dentigerous cyst removal with bone defect grafting and plating; however, because of wound dehiscence and allogeneic bone graft exposure, the patient required one additional procedure. Full article

Background: Bone defects resulting from trauma, infection, or benign tumors pose major challenges in orthopedic surgery. Traditional approaches, such as autologous bone grafting, are limited by donor site morbidity and graft availability. CERAMENT™, a synthetic bone substitute composed of calcium sulfate and hydroxyapatite, offers an alternative with osteoconductive properties, controlled resorption, and injectability. Methods: A scoping review was conducted in accordance with PRISMA-ScR guidelines. Literature searches were performed in PubMed, Embase, and Scopus through 3 July 2025, using the terms “CERAMENT™” and “Orthopedics.” Studies were selected based on the PICO framework, focusing on clinical applications of CERAMENT™ in human orthopedic procedures. Results: Out of 480 initial records, 22 studies met the inclusion criteria. CERAMENT™ demonstrated favorable outcomes in a range of orthopedic settings. In the CERTiFy trial, it was non-inferior to autologous grafting in tibial plateau fractures. CERAMENT™ achieved full wound healing and bone remodeling in chronic osteomyelitis. Additional studies reported positive outcomes in tumor-related defect reconstruction, spinal augmentation, and foot and ankle surgery, highlighting reduced surgical morbidity and faster recovery. Conclusions: CERAMENT™ offers a versatile, effective solution for bone reconstruction across multiple orthopedic domains. Its clinical performance, ease of use, and antimicrobial capabilities support its integration into routine orthopedic practice. Further research may refine its indications and long-term benefits. Full article

Background: Maxillomandibular bone defects present a complex challenge in regenerative medicine due to anatomical and functional intricacies. Calcium phosphate (CP)-based biomaterials have emerged as promising bone graft substitutes due to their biocompatibility, osteoconductivity, and bioactivity. Aim: This Review highlights recent clinical and experimental advancements in CP-based biomaterials for maxillomandibular bone regeneration, bridging the gap from bench to bedside. Method: An in vitro, in vivo, and clinical literature review was conducted to evaluate the performance of CP ceramics, including hydroxyapatite (HA), tricalcium phosphate (TCP), biphasic ceramics, and novel composites with polymers, growth factors, and nanoparticles. Results: Calcium phosphate-based biomaterials demonstrate excellent bone regeneration potential, with Beta-tricalcium phosphate (β-TCP) and HA being the most widely utilized. Composite scaffolds and 3-dimensional (3D)-printed constructs show enhanced mechanical properties and biological integration. Clinical trials have confirmed the safety and efficacy of CP-based materials, yielding promising outcomes in osteoconduction and defect healing. However, limitations persist regarding mechanical strength and long-term degradation profiles. Conclusions: CP-based biomaterials offer significant clinical promise for maxillomandibular bone regeneration. Continued advancements in scaffold design and biofunctionalization are crucial for overcoming current limitations and fully realizing their therapeutic potential. Full article

Silver nanoparticles (AgNPs) have attracted significant attention in recent years in diverse fields owing to their broad mechanisms of action. In particular, the wound healing process has become one of the main fields where the therapeutic potential of AgNPs is highlighted. AgNPs can be used as monotherapy or incorporated into composite structures in various formulations such as nanogels, hydrogels, powders, ointments, and sprays, for the treatment of a wide range of wound types including burns, excisional and incisional wounds, bone defects, surgical wounds, and diabetic ulcers. This widespread use is attributed to the strong antibacterial, anti-inflammatory, antioxidant, and cell proliferation-promoting biological properties of AgNPs. Moreover, AgNPs exhibit synergistic effects when combined with conventional antibiotics, enhancing their efficiency against resistant bacterial strains or even restoring the lost antibacterial activity. These biological properties enable AgNPs to reduce infection risk while simultaneously promoting high-quality healing by accelerating tissue regeneration. The therapeutic effectiveness of AgNPs is influenced by their physicochemical properties, including particle size, shape, and surface chemistry. In particular, synthesis methods play a significant role in determining both the biological activity and the safety profile of AgNPs. Among various methods, green synthesis approaches stand out for enabling the production of environmentally friendly, non-toxic, and highly biocompatible AgNPs. In this review, the mechanisms of action of AgNPs in wound healing are examined in detail, and recent scientific developments in this field are evaluated based on current in vitro, in vivo, and clinical studies. Full article

Shilajit, a natural herbo-mineral compound with potent antioxidant, anti-inflammatory, and osteogenic properties, has been traditionally used to promote tissue repair. However, limited experimental data exist on its localized application in bone regeneration. This study aimed to evaluate the combined effect of Shilajit and bovine-derived xenograft on bone healing in a rat tibial defect model. Twenty-eight male Sprague–Dawley rats were randomly assigned to four groups (n = 7): Control (defect left to heal spontaneously), Graft-only, Graft + Shilajit 150 mg/kg, and Graft + Shilajit 250 mg/kg. Standardized 3 mm tibial defects were created and filled with xenograft in all groups except the Control. Shilajit was administered intraperitoneally on days 0–3 postoperatively. After 4 weeks, serum total oxidant status (TOS), total antioxidant status (TAS), and TNF-α levels were measured. Tibial specimens underwent histopathological, histomorphometric, and TNF-α immunohistochemical analysis. High-dose Shilajit significantly increased TAS and reduced TOS compared with the Control and Graft-only groups (p < 0.001). Median TNF-α concentrations decreased in a dose-dependent manner, with the lowest values in the high-dose group (15.7 [14.3–17.1] pg/mL, p < 0.001). Histomorphometry revealed the highest new bone area percentage (78.1% [74.9–81.2]) and lowest fibrous tissue content (9.8% [8.1–11.6]) in the high-dose group. Immunohistochemistry confirmed marked suppression of TNF-α expression in Shilajit-treated groups, particularly at high doses. The combination of Shilajit and bovine-derived xenograft significantly enhanced bone regeneration in a dose-dependent manner, likely through antioxidative, anti-inflammatory, and osteogenic mechanisms. These findings suggest that Shilajit may serve as a promising adjunct in bone grafting procedures. Full article

Calvarial suture skeletal stem cells (Su-SSCs) are a distinct stem cell population for craniofacial bone formation by intramembranous ossification, compared to long bone periosteal SSCs (LB-PSSCs) with endochondral (osteochondrogenic) ossification. However, whether SSC intrinsic or extrinsic factors affect their differentiation process has not been well elucidated. Here, using an inducible Prx1-CreER-EGFP^+/−;Rosa26-tdTomato mouse model, we observed that endogenous Prx1⁺ Su-SSCs and their orthotopic transplantation into calvarial injury do not form cartilage intermediates at the injury sites, while the transplantation of Prx1⁺ LB-PSSCs into LB injury induces osteochondrogenic differentiation, respectively. However, the heterotopic transplantation of Prx1⁺ Su-SSCs (Su-SSCs into LB injury) showed some surprising findings that the transplanted Su-SSCs acquire new chondrocyte differentiation properties at the LB injury sites, although the heterotopic-transplanted Prx1⁺ LB-PSSCs maintained their endochondral ossification properties at the calvarial injury sites. Further, a comparative single-cell transcriptomic analysis of LB-PSSCs and Su-SSCs revealed that Su-SSCs express a higher set of anti-chondrogenic genes, such as Wnt5b, Twist1 while LB-PSSCs highly express chondrogenic Hoxa-9, Hoxc-9, Hoxa-10, Hoxc-10, and Comp genes. We also found that the heterotopic transplantation of LB-PSSCs into calvarial injury enhances bone healing in vivo. Taken together, these findings suggest that LB-PSSCs have high regenerative capability with invariable endochondral ossification even after the heterotopic transplantation but Su-SSCs are more flexible and regulated by the local bone environment. The transplantation of periosteal SSCs will be a promising method for large craniofacial bone defects. 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: The aim of this experimental pilot study was to evaluate the effect of pore volume and material composition on bone ingrowth into a resorbable poly-L-lactide-CaCO₃/CaP scaffold. Methods: Cylindric scaffolds of 7 mm diameter and 5 mm height and two different degrees of porosity were produced using selective laser sintering of poly-L-lactide-powder containing 24% CaCO₃ spherulites with and without surface modification with 4% CaP. Six minipigs received the four types of macroporous cylindrical scaffolds, inserted press fit into trephine defects of the tibial metaphyses, and left to heal for 4 and 13 weeks in three animals each. The specimens were evaluated using µCT for pore volume fill, and histomorphometry for bone formation and immunohistochemistry for expression of osteocalcin. Results: After 4 weeks, newly formed bone ranged from 2.73 mm² to 5.28 mm² mean total area. Mean pore volume fill varied between 12.25% and 20.35% and the average level of osteocalcin expression ranged from 2.49 mm² to 4.48 mm² mean total area. No significant differences were found between the different scaffolds. After 13 weeks, bone formation and pore fill volume had significantly increased in all scaffold groups up to a mean value of 14.79 mm² and 96.04%, respectively. Again, differences between the groups were not significant. Conclusions: The tested SLS produced scaffolds allowed for bone ingrowth, almost completely filling the pore volume after 13 weeks. Newly formed bone was in direct contact with the scaffold walls. Differences in pore volume did not account for significant differences in bone formation inside the scaffolds. The addition of CaP likewise did not lead to increased bone formation, most likely due to low availability of CaP to the biological environment. Full article

Background: NVD003 is an autologous, adipose tissue-derived stem cell-based tissue-engineered bone graft substitute with pro-osteogenic, anti-resorptive, and pro-angiogenic properties. Here, we describe highlights from the NVD003 preclinical development program as well as early clinical experience. Methods: NVD003 is produced in a Good Manufacturing Practice-controlled process from adipose stem cells collected during a minimally invasive liposuction procedure. The final implant is a ready-to-use moldable putty with fixed mineral content and predefined physiologic ranges of osteogenic cells and bioactive growth factors. Preclinical pharmacology studies were conducted in nude rats using a paravertebral implantation model, and subsequently, in a femoral critical-sized bone defect (CSBD) model. In a first-in-human Phase 1b/2a study, NVD003 was used for fracture osteosynthesis with classical fixation material in nine adults with recalcitrant lower limb non-union. NVD003 was also used at the discretion of treating physicians in four pediatric patients surgically treated for congenital pseudarthrosis of the tibia (CPT) with the Masquelet technique. Efficacy was evaluated as clinical healing and in terms of bone formation, bone union, and bone remodeling on radiographs and computed tomography using the extended Lane and Sandhu Scale. Results: Preclinical studies indicated that NVD003 requires cellularity for its bioactivity and moreover facilitates bone union when used as a graft material in femoral CSBD. In the clinical study, nine adult participants were successfully grafted with NVD003 and completed study follow-up to 24 months, with extended safety follow-up to 5 years ongoing. No adverse events were considered related to NVD003. Maximal bone formation occurred between 3 and 12 months post-implantation; the mean time to clinical healing was 6 months and the mean time to radiological union was 17 months. Ultimately, 89% (8/9) of patients achieved bone union without refracture. All four pediatric patients with CPT also achieved lasting bone union following grafting with NVD003. No safety signals were observed over a mean follow-up of 62.1 months. Conclusions: NVD003 represents a safe, autologous bone graft substitute product without side effects of heterotopic ossification or bone resorption. NVD003 facilitated bone union in adult and pediatric patients even under severe pathophysiological conditions. Full article

Objectives: The presence of gingival buccal recession is a frequent problem especially in the canine area. The cortical buccal bone may be absent in presence of health normal lingual/palatal bone and of other periodontal pockets. The present case report describes a minimally invasive approach in a 76-year-old patient with previously endodontically treated lower canine affected by root fracture and by a serious chronic buccal recession. Methods: The tooth was characterized by a deep vestibular bone defect, lack of buccal bone and acute periapical lesion. After extraction, Maryland bridge was positioned on the edentulous area. A two-piece convergent neck transmucosal implant was inserted with a flapless approach after 6 months. Maryland bridge was left in place for additional 3 months. After this time, digital impressions were taken, and a customized abutment was positioned. A provisional crown was designed according to Biologically Oriented Preparation Technique (BOPT) concept and maintained for 6 months. A zirconia definitive crown was digitally designed and cemented with a polycarboxylate-based cement. The Pink Esthetic Score (PES) was used as an index to assess peri-implant soft tissue stability over time (preoperatively, at 9 months, at 12 months and 72 months). Results: The patient was followed for 6 years under a conventional hygienic recall program. No complications occurred, and the PES improved from 4 preoperatively to 8 at 9 months, 10 at 12 months and 13 at 72 months. Conclusions: The use of Maryland bridge prevented occlusal trauma on healing tissues and appeared to support bone and soft tissue healing for transmucosal implant placement. A stable aesthetic rehabilitation was achieved up to 6 years. Full article

Background: Bone regeneration is a key therapeutic objective in periodontology, particularly in the treatment of alveolar defects caused by periodontal disease, dentoalveolar trauma, or surgical interventions. Among current regenerative strategies, collagen-enriched biomaterials have demonstrated an active role in modulating cellular behavior during bone repair. However, the specific effects of different collagen formulations on human dental pulp stem cells (hDPSCs) have not yet been fully characterized. Objective: To evaluate the impact of xenogeneic bone grafts with and without collagen—OsteoBiol^® Gen-Os^® (GO), OsteoBiol^® GTO^® (GTO), and Geistlich Bio-Oss^® (BO)—on cell viability, adhesion, migration, osteogenic differentiation, and mineralization potential of hDPSCs, and to explore the molecular mechanisms underlying their effects. Methods: In vitro assays were conducted to assess viability (MTT and fluorescence staining), adhesion (SEM), migration (wound healing assay), and mineralization (Alizarin Red S staining). Gene expression analyses (RT-qPCR) were performed for adhesion/migration markers (FN, SDF-1, COL1A1), angiogenic/proliferation markers (VEGF, FGF2), and osteogenic differentiation markers (RUNX2, ALP, COL1A1). Results: GO showed a higher early expression of genes associated with adhesion, migration, angiogenesis (FN, SDF-1, VEGF and FGF2: p < 0.05; COL1A1: p < 0.01), and osteogenic differentiation (7 days: COL1A1 and ALP (p < 0.001)); (14 days: RUNX2, ALP: p < 0.001; COL1A1: p < 0.05), indicating a sequential activation of molecular pathways and mineralization capacity comparable to the control group. GTO demonstrated the best biocompatibility, with significantly higher cell viability (p < 0.05), strong adhesion, and markedly increased mineralization at 21 days (p < 0.001), despite moderate early gene expression. BO showed reduced cell viability at 10 mg/mL (p < 0.05) and 20 mg/mL (p < 0.001), with mineralization levels similar to the control group. Conclusion: Collagen-based xenografts demonstrate favorable interactions with hDPSCs, enhancing viability and promoting osteogenic differentiation. Our findings suggest that beyond the presence of collagen, the specific formulation of these biomaterials may modulate their biological performance, highlighting the importance of material design in optimizing regenerative outcomes. Clinical Significance: The formulation of collagen in xenogeneic bone substitutes may be a determining factor in enhancing periodontal regenerative outcomes by modulating the early cellular response and osteogenic activity in stem cell-based tissue engineering. Full article

This study aimed to investigate the effect of enamel matrix derivatives (EMD) on the early healing biomarkers’ expression following flapless treatment. Thirty-eight patients with residual deep intrabony defects after steps 1 and 2 of periodontal therapy were randomly assigned to the test (flapless with EMD) or control group (flapless alone). Periodontal parameters were recorded at baseline and 6 months after treatment. Gingival crevicular fluid (GCF) was collected at baseline and 2 weeks after treatment to quantify the levels of biomarkers related to epithelial healing (epidermal growth factor, EGF), connective tissue healing (matrix metalloproteinase-8 [MMP-8], fibroblast growth factor [FGF], transforming growth factor-β [TGF-β]), and bone formation (osteoprotegerin [OPG]). The test group showed a significant reduction in MMP-8 levels (p = 0.039), along with significant increases in EGF (p < 0.01), FGF (p < 0.01), and OPG (p < 0.01). The control group demonstrated a significant decrease in MMP-8 (p = 0.010). No significant changes in TGF-β levels were observed in either group. At 6 months, the test group exhibited significantly greater reductions in probing pocket depth and clinical attachment level compared to the control group. This study is the first to characterize the biochemical changes following flapless treatment with EMD. These preliminary findings suggest that EMD may enhance early wound healing by modulating the expression of key regenerative biomarkers. Full article