Search Results (562)

Background: Osteoinduction and bone regeneration are fundamental biological mechanisms enabling osseointegration and long-term durability of endosseous dental implants. In clinical practice, poor bone conditions, aesthetic demands, and peri-implant soft tissue problems commonly need the utilization of regenerative techniques targeted at optimizing both hard and soft tissue results. The purpose of this narrative review was to examine osteo-inductive and regenerative strategies currently employed in implant dentistry, with particular emphasis on the mechanobiological integration of hard–soft tissue regeneration and its implications for peri-implant tissue stability, osseointegration, and clinical predictability. Methods: A narrative literature review was done using PubMed and Scopus databases. Based on predetermined inclusion and exclusion criteria, studies published in English during the previous five years were reviewed. The core narrative analysis comprised a selection of physiologically relevant research that addressed osteo-inductive techniques, bone regeneration, osseointegration, and peri-implant soft tissue outcomes, as well as clinical studies, randomized controlled trials, systematic reviews, and narrative reviews. A narrative synthesis was carried out because of methodological variability. Special emphasis was placed on evidence addressing the biological and clinical interaction between hard- and soft-tissue regenerative strategies, reflecting the specific conceptual focus of the review. Results: The evidence presented suggests that implant surface biofunctionalization, biologically active grafting materials, guided bone regeneration, and supplementary biological treatments may have a favorable impact on implant stability and peri-implant bone healing. Several investigations also underlined the biological dependency between peri-implant bone regeneration and soft tissue architecture, stressing the significance of soft tissue thickness, keratinized mucosa, and emergence profile stability. Even in inflammatory environments, bioactive titanium surface changes showed osteogenic potential, indicating a supporting function in early osseointegration. Conclusions: By promoting osseointegration and improving peri-implant tissue outcomes, osteo-inductive and regenerative techniques are essential to modern implant dentistry; however, their greatest potential may lie in integrated hard–soft tissue regenerative approaches aimed at improving long-term clinical predictability. To further understand the clinical efficacy of combination hard–soft tissue regeneration methods, future well-designed clinical trials with standardized outcome measures are needed. Future research should further clarify the mechanobiological principles underlying these integrated regenerative approaches. Full article

Background/Objectives: Guided bone regeneration (GBR) in dental applications requires scaffolds that possess balanced mechanical strength, controlled biodegradability, and excellent biological performance; therefore, this study aims to develop and evaluate a multilayered biofunctional dental membrane designed to enhance mechanical, biological, and antibacterial performance. Methods: The multilayered membrane was fabricated using sequential electrospinning and electrospraying techniques to form a polycaprolactone (PCL)/Collagen first layer and a polyvinyl alcohol (PVA)/Collagen/Hydroxyapatite (HAp) second layer, topped with a final electrospray coating of PVA/Amoxicillin. Characterization was performed via SEM, FTIR, and EDS, followed by evaluations of tensile properties, swelling behavior, hydrolytic degradation, in vitro drug release, disk diffusion antibacterial activity against Staphylococcus aureus and Escherichia coli, and 7-day L929 fibroblast cytocompatibility (ANOVA/Tukey, p < 0.05). Results: SEM, FTIR, and EDS analyses confirmed uniform nanofiber morphology, homogeneous HAp distribution, and successful integration of bioactive compounds. The membrane exhibited a maximum tensile strength of 15.17 N, strain of 25.24%, and stress of 2.16 MPa, while swelling reached ~100% within 2 h and degradation stabilized around 4% weight loss after 48 h. Drug release profiles showed a rapid amoxicillin release in the first 50 min, plateauing at approximately 4.5 mg/L by 350 min, with distinct antibacterial inhibition zones, and the PCL/Col–PVA/Col/HAp–PVA/Amox group demonstrated the highest cell viability (~140%) after 7 days, significantly exceeding the control groups (p < 0.01). Conclusions: These quantitative findings validate the fabricated multilayered membrane’s potential as a mechanically robust, biodegradable, antibacterial, and bioactive scaffold for advanced guided bone regeneration in dental applications. Full article

Full-arch implant-supported rehabilitations are widely recognized as an effective treatment option for edentulous patients. Nevertheless, clinical decision-making regarding patient selection, surgical planning, prosthetic material choice, and long-term maintenance protocols remains heterogeneous and requires structured evidence-based guidance. A modified Delphi consensus process was conducted involving 29 experts during the Italian Consensus Conference. A systematic literature review covering the period 2015–2024 was performed, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Consensus was predefined as ≥90% agreement. Seven evidence-based consensus statements were developed addressing: (1) periodontal risk assessment using validated tools; (2) guided bone regeneration outcomes with technique-specific indications; (3) comparative survival of four versus six implants in mandibular full-arch rehabilitations; (4) equivalence of tilted and axial implant configurations; (5) prosthetic material selection, with monolithic zirconia showing high survival; (6) risk-stratified supportive maintenance protocols associated with a reduction in peri-implantitis incidence; and (7) systemic risk stratification, including absolute and relative contraindications, medication-related osteonecrosis of the jaw (MRONJ) risk management, and perioperative antibiotic prophylaxis. Full article

Background/Objectives: Titanium implants remain the gold standard in implant dentistry. However, growing interest in metal-free alternatives has led to increased use of zirconia implants. Despite encouraging short-term outcomes, evidence regarding the medium- to long-term survival of one-piece zirconia implants (O-PZIs) and associated risk factors remains limited. The aim of this retrospective cohort study was to evaluate the survival of O-PZIs over follow-up periods of up to 8 years and to explore variables potentially associated with implant failure. Methods: This retrospective observational cohort study was conducted at a private dental clinic (Madrid, Spain). A total of 307 O-PZIs placed in 196 patients between 2017 and 2021 were analyzed. Implant survival was assessed using Kaplan–Meier analysis, while associations between clinical variables and implant failure were explored using chi-square tests and multivariate Cox regression models (p < 0.05). The mean follow-up period was 61.37 ± 2.25 months. Results: After a mean follow-up of 61.37 ± 2.25 months (range: 39–96 months), 42 failures were recorded, resulting in a cumulative survival rate of 86.32% (CI 95%: 79.28–92.96%). Most failures (64.29%) occurred before prosthetic loading. Kaplan–Meier analysis revealed significantly lower survival for tapered implants (p < 0.001) and among smokers (p < 0.001). Multivariate analysis indicated that only simultaneous guided bone regeneration (GBR) was independently associated with implant failure (Exp(B) = 3.191; 95% CI: 1.299–7.840; p = 0.011). However, this association should be interpreted with caution due to the retrospective design, potential confounding, limited number of events, and lack of adjustment for clustering at the patient level. The discrepancies observed between statistical methods highlight the importance of time-to-event analyses in implant research. Conclusions: Within the limitations of this study, O-PZIs demonstrated acceptable medium- to long-term survival. Simultaneous GBR may be associated with increased risk of failure. However, these findings should be considered exploratory. Further prospective studies are required to confirm these results and to better define risk factors in ceramic implant therapy. Full article

Background: Platelet concentrates (PCs), including platelet-rich fibrin (PRF) and its derivatives, have been increasingly investigated as autologous adjuncts in alveolar and periodontal regenerative procedures. This systematic review aimed to evaluate whether PCs improve clinical, radiographic, and histological outcomes compared with conventional regenerative approaches. Methods: A comprehensive search of PubMed, Scopus, and Web of Science identified randomized clinical trials on intrabony and furcation defects, alveolar ridge preservation, alveolar cleft reconstruction, and periodontally accelerated osteogenic orthodontics (PAOO). Sixteen studies met the inclusion criteria. Results: Overall, PCs, used alone as membranes or in combination with allograft materials, have been associated with significant clinical and radiographic improvements, with three main patterns of effect emerging across studies: (i) adjunctive benefit in selected outcomes (e.g., ridge width preservation and new bone formation when PRF was combined with graft materials); (ii) non-inferiority or equivalence compared with conventional regenerative approaches, particularly in periodontal intrabony defects; and (iii) lack of consistent superiority, as several studies reported comparable outcomes to standard techniques rather than clear advantages. In cleft reconstruction, PRF used in combination with allografts has shown comparable or non-inferior results to standard graft approaches, potentially reducing morbidity. Despite these favorable trends, evidence has been mixed in terms of platelet preparation protocols, defect types, additional biomaterials, and length of follow-up. The heterogeneity of the included studies and the absence of quantitative synthesis limit the strength of the conclusions. Conclusions: Within these limitations, PCs appear to represent a valid complement or alternative to conventional regenerative strategies, primarily as an adjunct rather than a clearly superior approach, and further well-designed randomized clinical trials with standardized protocols and longer follow-up are needed to strengthen clinical recommendations. Full article

Objectives: This study aimed to compare vertical bone gain (VBG) and horizontal bone gain (HBG) after guided bone regeneration using titanium-reinforced dense PTFE (TiR-dPTFE) versus reinforced PTFE mesh (RPM) at 9 and 12 months on three-dimensional tomographic imaging, and to perform histological assessment in selected cases. Materials and Methods: This prospective comparative case series included 14 patients (46 vertical ridge defect sites) treated with guided bone regeneration using either Ti-reinforced dPTFE membranes (TiR-dPTFE; n = 23) or resorbable porcine collagen membranes (RPM; n = 23). All sites received a 60:40 mixture of autogenous bone chips and anorganic bovine bone mineral (ABBM). After 9 months, during implant placement, a protective secondary augmentation using a 70:30 ABBM/autogenous mixture was performed and covered with a collagen membrane. Vertical and horizontal bone gain (VBG, HBG) were assessed on standardized matched CBCT cross-sections obtained at 9 and 12 months. Core biopsies were harvested at implant placement (9 months) for histological evaluation. Surgical and healing complications were recorded. Results: Both membranes produced significant VBG. TiR-dPTFE achieved greater VBG than RPM at 9 months (p = 0.045) and 12 months (p = 0.012) and remained stable from 9 to 12 months, whereas RPM showed a significant decline over time (MDa −0.48 mm; 95% CI −0.64 to −0.31; p < 0.001). HBG was similar between groups at both time points (p = 0.918 and p = 0.922). No major clinical complications occurred. Histology at 9 months confirmed vital bone formation and graft integration in both groups. Conclusions: Both TiR-dPTFE and RPM are reliable options for vertical ridge augmentation; TiR-dPTFE yielded superior and more stable vertical gains over 12 months, with comparable horizontal outcomes. Clinical Relevance: TiR-dPTFE may offer enhanced vertical augmentation, while both membranes remain suitable for implant site development. Full article

The manuscript details the influence of high-temperature and high-shear processing, as well as radiation sterilization, on properties of bioresorbable and osteoconductive, patient-tailored alloplastic scaffolds for guided bone regeneration. Functionalized poly(l-lactide-co-d,l-lactide) copolymer filled with hydroxyapatite was used to produce two personalized implants for upper and lower jaw reconstruction via 3D printing. Morphology analysis (SEM, µCT), gel permeation chromatography, and thermal analysis quantified the effects of melt processing and sterilization on chain structure. Physical properties of sterilized parts, such as hardness and density, proved suitable for bone implants. Removal of the upper jaw implant after 4 months and of the lower jaw substitute after 18 months enabled monitoring of bioresorption and tissue regrowth over time. Gradual overgrowth of the implants with human tissue, initiated by the osteoconductive filler, was observed, along with time-dependent polylactide degradation, showing up to 92% molar mass reduction. The medical procedures confirmed safety, nontoxicity, non-allergenicity, and, most importantly, the tissue-forming properties of the polylactide-based formulation. Full article

Mineral powder–based bone grafts exhibit excellent osteoconductivity; however, their clinical efficacy is often compromised by insufficient early-stage tissue ingrowth, leading to particle aggregation and pocket formation within the defect site during the initial healing phase. Here, we report a cotton-type nanofiber-guided mineral graft designed to overcome this early integration failure by creating fibrous pathways for tissue ingress. Cotton-type polycaprolactone (PCL) nanofibers were fabricated via electrospinning using a pin-based collector engineered to induce strong inter-fiber repulsion, resulting in a highly expanded, three-dimensional cottony architecture. Tetracalcium phosphate (TTCP) and α-tricalcium phosphate (α-TCP) mineral particles were subsequently deposited onto the surface of the cottony nanofibers, forming a fibrous–mineral hybrid graft (c-NF@T/α-TCP) in which the nanofibers act as a transient, functionally defined tissue-guiding framework during the early healing phase. The cottony nanofiber network effectively prevented mineral particle aggregation and generated continuous pathways within the graft, facilitating early tissue infiltration and vascular ingress during the first week after implantation. In vivo evaluation in a bone defect model demonstrated that c-NF@T/α-TCP significantly reduced tissue pocket formation at early time points and promoted subsequent bone regeneration compared to mineral powder-only grafts. This study highlights the critical importance of early-stage structural guidance in mineral-based bone grafts and introduces cotton-type nanofiber–guided pathway engineering as a simple yet effective strategy to unlock the regenerative potential of conventional inorganic bone substitutes. Full article

Background/Objectives: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). Materials and Methods: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. Results: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. Conclusions: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This “parallel differentiation” platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications. Full article

Periodontal disease represents a major global health burden, beginning with gingivitis and progressing to periodontitis, which causes connective tissue breakdown, alveolar bone resorption, and eventual tooth loss. Beyond local pathology, periodontitis is a chronic inflammatory condition with systemic associations, including cardiovascular disease, diabetes, and metabolic disorders. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have emerged as promising candidates for periodontal regeneration. This review aimed to map the current evidence on MSC-derived EVs (MSC-EVs) in periodontal regeneration, focusing on their mechanisms of action, therapeutic potential, and translational challenges. A comprehensive literature search was conducted across a major biomedical database (PubMed) to identify preclinical and clinical studies investigating MSC-EVs in the context of periodontitis. Data were charted on EV cargo composition, biological functions, regenerative outcomes, and reported limitations. Evidence indicates that MSC-EVs encapsulate bioactive molecules—including antimicrobial peptides, proteins, lipids, and microRNAs—that modulate immune responses, suppress pro-inflammatory signaling, and promote angiogenesis and tissue repair. In periodontal models, MSC-EVs attenuate osteoclast activity, enhance fibroblast proliferation, and stimulate extracellular matrix remodeling, supporting regeneration of periodontal ligament and alveolar bone. Exosome-based approaches demonstrate advantages such as reduced immunogenicity, improved safety, and feasibility for storage and standardization. However, most findings remain preclinical, with limited human data available. To bridge the translational gap, well-designed clinical trials are needed to confirm efficacy and safety while addressing regulatory challenges, GMP standards, and outcome measures. Harnessing their regenerative capacity while mitigating side effects may guide precision-targeted therapies, and continued mechanistic studies with standardized production will be key to advancing MSC-EVs into clinical practice. Full article

Treatment for large critical-sized bone defects and impaired fracture healing remain challenging. Clinically used protein-based osteoinductive factors, such as recombinant bone morphogenetic proteins (BMPs), can be effective; however, they are costly and limited by stability, dose-delivery issues, and safety concerns. Preclinical small molecules offer an alternative because they are chemically stable, scalable to manufacture, and readily integrated for systemic administration or localized release from scaffolds, hydrogels, cements, and implant coatings. With an emphasis on delivery formats and mechanistic themes, this review examines small molecules that have been shown to improve bone regeneration in preclinical models, contrasting those of biological origin with synthetic and repurposed compounds. Across studies, these selected compounds promote osteoblast commitment, differentiation, and matrix mineralization via BMP/Smad signaling and Wnt/beta-catenin (β-catenin) activation, often through glycogen synthase kinase-3 beta (GSK-3β) inhibition or relief of pathway antagonism or Hedgehog (Hh) pathway stimulation. Beyond osteoinduction, several candidates address issues that commonly limit repair, including angiogenesis, oxidative stress, inflammatory tone, osteoimmune regulation, and suppression of osteoclast-mediated resorption. Direct head-to-head comparisons are rare across both classes and reporting heterogeneity complicates interpretation. Key translational gaps include limited cytotoxicity and immunologic profiling, dose and release optimization, durability of benefit, and insufficient evaluation of rational combinations. More rigorous in vivo studies, including larger animal models and standardized outcome metrics, are needed to prioritize promising candidates and guide clinical development. Full article

Background: This study compared two xenogeneic bone graft materials, A-Oss (bovine-derived) and The Graft (porcine-derived), using a rabbit calvarial defect model and a canine mandibular dehiscence-type defect model. Methods: Healing was evaluated at 6 and 12 weeks in rabbits and at 24 weeks in mongrel dogs. Micro-computed tomography quantified mineralized tissue fill (defect closure) in rabbits and, in dogs, the compartments classified as new bone and residual graft, together with vertical and horizontal volumetric maintenance. Hematoxylin and eosin (H&E) sections provided complementary qualitative observations. Results: In rabbits, defect closure did not differ between materials at 6 weeks (67.1 ± 12.7% vs. 70.2 ± 15.1%, p = 0.090) or 12 weeks (78.6 ± 5.9% vs. 72.3 ± 0.9%, p = 0.124). In dogs, new bone was similar between groups (43.5 ± 3.2% vs. 45.9 ± 1.1%, p = 0.208), whereas residual graft showed a numerical trend toward higher values with A-Oss (20.2 ± 3.5% vs. 13.3 ± 4.5%, p = 0.069). Vertical volume maintenance also trended higher with A-Oss (91.1 ± 1.6% vs. 87.8 ± 1.3%, p = 0.056), while horizontal maintenance was comparable (94.5 ± 1.8% vs. 91.4 ± 2.8%, p = 0.241). Histology in both models showed graft particles within the defect/augmented regions with surrounding eosinophilic matrix and intervening tissue spaces. Conclusions: Overall, both materials produced similar healing profiles across models, with small between-material differences most apparent in the canine dehiscence setting. Full article

Background/Objective: Advanced peri-implantitis presents a significant challenge in contemporary implant dentistry and sometimes necessitates implant removal when regenerative therapies are no longer reliable. Protocols for staged bone reconstruction, re-implantation, and definitive prosthetic rehabilitation following peri-implantitis continue to evolve. This study aims to present a clinical case of advanced peri-implantitis with vertical interproximal bone loss managed with a staged surgical and prosthetic approach and review current concepts in implant removal, bone regeneration, re-implantation, and soft-tissue management. Methods: A patient with peri-implantitis affecting two maxillary implants underwent treatment over one year. The initial surgical stage included removal of the failing implants and reconstruction of the defects using guided bone regeneration with a composite graft of 50% xenogeneic bone substitute and 50% autogenous bone, covered by a barrier membrane. After six months of healing, a second surgical stage was performed, involving placement of two new implants in positions 2.2 and 2.4, additional bone augmentation, and soft tissue grafting to enhance soft tissue volume and the width of keratinized gingiva following mucogingival line rebounce. After an additional six months of osseointegration, full maxillary prosthetic rehabilitation was completed in August 2025. Results: Clinical and radiographic assessments demonstrated successful bone regeneration, stable implant integration, adequate peri-implant soft-tissue conditions, and favorable functional and esthetic outcomes at follow-up. The case is discussed in the context of current evidence regarding indications for implant removal, regenerative strategies after explantation, timing of re-implantation, and the importance of keratinized gingiva and prosthetic design in long-term peri-implant health. Conclusions: Staged explantation, guided bone regeneration, delayed re-implantation, and comprehensive soft-tissue and prosthetic management may represent a viable treatment strategy in selected cases of advanced peri-implantitis. Full article

Adequate alveolar bone volume is a prerequisite for predictable and long-term success in dental implant therapy. Physiological post-extraction remodeling frequently results in horizontal and vertical ridge deficiencies, which may compromise optimal implant placement. Guided bone regeneration (GBR) has become a cornerstone procedure in implant dentistry, with clinical outcomes largely influenced by the biological and mechanical characteristics of grafting materials. Different bone grafts and their combinations are currently clinically applicable, each exhibiting distinct osteogenic, osteoinductive, and osteoconductive properties, as well as varying resorption profiles and volumetric stability. This narrative review aims to analyze the biological principles of alveolar ridge augmentation, compare the properties of commonly used graft materials, evaluate clinical outcomes, and discuss emerging regenerative strategies. Literature published between 2000 and 2025 was assessed to synthesize current evidence regarding graft integration, bone formation, desorption dynamics, and clinical indications. Autogenous bone remains the gold standard due to its combined osteogenic, osteoinductive, and osteoconductive potential; however, its limitations have driven the development of alternative materials, including allografts, xenografts, alloplastic substitutes, demineralized tooth matrices, platelet concentrates, and customized scaffolds. While no single material is universally ideal, appropriate selection based on defect characteristics and clinical objectives is essential for predictable outcomes. Future research should prioritize long-term comparative trials, biomaterial standardization, and biologically enhanced regenerative approaches. Full article

Nanostructured calcium phosphate-based (CaP) biocomposites have proven to be ideal candidates for the creation of multifunctional systems with applications in biomedicine. This review presents a critical and integrative overview of recent advances in the synthesis of CaP nanocomposites with applications in bone tissue regeneration. An analysis of calcium phosphate-based nanocomposites is thus provided by correlating their composition, synthesis routes and biological properties, guiding the rational development of next-generation biomaterials for bone tissue engineering. The first section presents calcium phosphates, such as hydroxyapatite (HAp) or β-tricalcium phosphate (β-TCP), used in the preparation of nanocomposite materials. Next, the main biocomposite materials are analyzed as a result of the functionalization of calcium phosphates by metal ion substitutions or by the addition of polymers, bioglass or metal additives. Thus, biomaterials with excellent properties in applications such as tissue engineering have been obtained. The synergistic effect of materials in the composition of biocomposites favored the improvement of properties such as bioactivity, mechanical strength, antimicrobial activity, structure and porosity. Beyond classical osteoconductivity, CaP-based nanocomposites demonstrate a broad spectrum of biological activities like immunomodulatory effects, pro-healing signaling, anti-inflammatory pathways, antibacterial and antifungal mechanisms, and capabilities for precise drug delivery or theranostic applications. Full article