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67 pages, 2869 KB  
Review
Physical and Mechanical Characterisation of 3D-Bioprinted Hydrogels for Dental Applications: A Scoping Review
by Nur Haziqah Junaidi, Nurulhuda Mohd, Noor Hayaty Abu Kasim and Masfueh Razali
Gels 2026, 12(6), 524; https://doi.org/10.3390/gels12060524 - 11 Jun 2026
Viewed by 132
Abstract
Recent advances in three-dimensional (3D)-bioprinted hydrogels show promise for overcoming the limitations of conventional techniques for dental tissue regeneration. This scoping review systematically analyses the physical, mechanical, and rheological properties of these hydrogels in dental applications, aiming to identify knowledge gaps, limitations, and [...] Read more.
Recent advances in three-dimensional (3D)-bioprinted hydrogels show promise for overcoming the limitations of conventional techniques for dental tissue regeneration. This scoping review systematically analyses the physical, mechanical, and rheological properties of these hydrogels in dental applications, aiming to identify knowledge gaps, limitations, and current and future directions for advancing and translating hydrogel-based 3D bioprinting in dentistry. In accordance with PRISMA-ScR guidelines, a comprehensive literature search was conducted across Ovid, PubMed, EBSCOhost, and Web of Science up to January 2026. Included studies focused on (i) 3D-bioprinted hydrogels, (ii) quantitative characterisation, and (iii) dental tissue engineering. A total of twenty-one studies met the inclusion criteria. The findings revealed substantial variability in formulations and properties. Gelatine-based hydrogels reinforced with β-tricalcium phosphate demonstrated the highest compressive strength within the range of cancellous bone, whereas GelMA/PEGDA composites exhibited tunable stiffness suitable for soft tissue applications. Extrusion-based bioprinting emerged as the predominant method, with photocrosslinking and ionic crosslinking as the primary gelation techniques. Biodegradation rates varied notably with composition and regenerative objectives. This review uniquely consolidates the physical, mechanical, and rheological evaluations of 3D-bioprinted hydrogels for dental applications. The review highlights critical gaps in methodological standardisation and validation, emphasising the importance of biomaterial selection to optimise scaffolds and regenerative outcomes in periodontal, bone, and pulp tissue engineering. Full article
(This article belongs to the Special Issue Functional Gels for Dental Applications)
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27 pages, 2796 KB  
Review
Osteoimmunology of Natural and Synthetic Biomaterials Used in Dentistry for Bone Remodeling
by Karla Lizeth Santana-Arenas, Tanya A. Camacho-Villegas and Pavel H. Lugo-Fabres
Macromol 2026, 6(2), 41; https://doi.org/10.3390/macromol6020041 - 9 Jun 2026
Viewed by 204
Abstract
Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural [...] Read more.
Bone loss in the maxillofacial region arises from multiple causes, including periodontal disease, trauma, surgical procedures, infection, congenital anomalies, and cancer. Traditional treatment relies on bone grafting, either alone or in combination with biomaterials. Advances in tissue engineering have introduced synthetic or natural scaffolds to mimic the mineralized bone matrix. Natural scaffolds offer excellent biocompatibility and similarity to native tissue but often lack sufficient mechanical strength and exhibit poor degradation rates. Synthetic scaffolds provide tunable porosity and mechanical stability; however, their biological inertness makes them poor sources of osteogenic signaling. A key factor in the success of any scaffold is its interaction with the host immune system. Upon implantation, the innate immune response is initiated, with neutrophils and macrophages being the first cells to contact the scaffold. Macrophage polarization toward proinflammatory (M1) or anti-inflammatory (M2) phenotypes determines whether the microenvironment favors inflammation or remodeling. The adaptive immune response also plays a critical role: T and B lymphocytes may promote tolerance and integration through Th2/Treg pathways and antibody-mediated regulation, or they may trigger chronic inflammation and rejection through Th1/Th17 activation. This review examines the natural and synthetic materials used for bone remodeling and their biological properties. It then outlines the sequence of immune events occurring from the moment a scaffold is implanted to its potential integration or failure. Finally, this study highlights the relevance of cellular models and in vitro assays for the early evaluation of immunogenicity and biocompatibility, which are essential for optimizing scaffold design and improving outcomes in maxillofacial bone regeneration. Full article
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24 pages, 7974 KB  
Systematic Review
Scaffold-Based Biomaterials for Periodontal Regeneration in Periodontitis: A Systematic Review and Meta-Analysis
by Felicia Gabriela Beresescu, Simona Mucenic, Adriana Monea, Andrea Bors and Liana Beresescu
J. Funct. Biomater. 2026, 17(6), 286; https://doi.org/10.3390/jfb17060286 - 8 Jun 2026
Viewed by 541
Abstract
Background: Periodontitis is characterized by loss of the periodontal ligament, cementum, and alveolar bone. Scaffold-based biomaterials are intended to provide a three-dimensional framework for periodontal wound stabilization and tissue regeneration, but their incremental clinical benefit over conventional regenerative therapy remains uncertain. This systematic [...] Read more.
Background: Periodontitis is characterized by loss of the periodontal ligament, cementum, and alveolar bone. Scaffold-based biomaterials are intended to provide a three-dimensional framework for periodontal wound stabilization and tissue regeneration, but their incremental clinical benefit over conventional regenerative therapy remains uncertain. This systematic review and meta-analysis evaluated scaffold-based periodontal regenerative procedures for probing depth (PD) reduction, clinical attachment level (CAL) gain, and radiographic defect fill compared with conventional treatment. Methods: Original randomized controlled trials published from January 2020 to 1 March 2026 were searched in MEDLINE (Ovid), Embase, CENTRAL, and Web of Science, screened in Rayyan, and meta-analyzed in RevMan v5.4. Certainty was evaluated using GRADE. Results: Thirty-one studies were included. Scaffold-based interventions produced statistically significant but clinically modest PD reductions at 6 months (MD = −0.27 mm; 95% CI: −0.43 to −0.10; p = 0.001; I2 = 34%) and 12 months (MD = −0.21 mm; 95% CI: −0.41 to −0.01; p = 0.04; I2 = 22%), but not at 24 months. The overall PD effect was small (MD = −0.26 mm; p < 0.0001). CAL gain was not significant at 6 or 12 months but was significant at 24 months (MD = 1.00 mm; p < 0.0001; I2 = 0%). Defect fill improved at 12 months (MD = 0.51 mm; p = 0.02) but not at 6 months. Subgroup and meta-regression analyses did not identify significant effects of scaffold type or PRF/PRP enrichment (p > 0.05). Conclusions: Scaffold-based biomaterials may provide limited, time-dependent clinical and radiographic benefits as adjuncts to conventional periodontal regenerative therapy. The evidence remains constrained by heterogeneous interventions, modest effect sizes, low-to-very-low certainty for several outcomes, and a paucity of histologic confirmation of true periodontal regeneration. Full article
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41 pages, 3003 KB  
Review
Advances and Challenges in Tissue Engineering: Biomaterials, Cellular Strategies, and Clinical Applications
by Rosana Farjaminejad, Samira Farjaminejad, Franklin Garcia-Godoy, Anand Marya, Ludovica Nucci and Abdolreza Jamilian
J. Funct. Biomater. 2026, 17(4), 184; https://doi.org/10.3390/jfb17040184 - 10 Apr 2026
Cited by 1 | Viewed by 1208
Abstract
Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides [...] Read more.
Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides a comprehensive overview of recent advances in scaffold design, highlighting natural, synthetic, and hybrid materials, as well as innovative fabrication techniques such as electrospinning, 3D bioprinting, and smart biomaterials. It discusses the role of stem cells and growth factors in directing regeneration and examines a wide range of clinical applications, including skin regeneration, cartilage repair, bone tissue engineering, dental and periodontal regeneration, nerve repair, cardiac tissue engineering, liver tissue models, and ophthalmic applications. Current challenges, such as immune responses, limited vascularization, scalability, and regulatory barriers, are addressed alongside emerging strategies aimed at improving clinical translation. By integrating diverse tissue types and engineering approaches within a unified framework, this review offers a broad yet detailed perspective on the current state and future directions of regenerative medicine. Full article
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24 pages, 1404 KB  
Review
Three-Dimensional Printing in Dentistry: Evolution, Technologies, and Clinical Application
by Citra Dewi Sahrir, Chin-Wei Wang, Yung-Kang Shen and Wei-Chun Lin
Polymers 2026, 18(7), 785; https://doi.org/10.3390/polym18070785 - 24 Mar 2026
Cited by 2 | Viewed by 1857
Abstract
Three-dimensional (3D) printing, also known as additive manufacturing (AM), has become increasingly integrated into dentistry because of its high precision, efficiency, and ability to fabricate patient-specific devices. This review comprehensively discusses the historical development of 3D printing and outlines the fundamental principles of [...] Read more.
Three-dimensional (3D) printing, also known as additive manufacturing (AM), has become increasingly integrated into dentistry because of its high precision, efficiency, and ability to fabricate patient-specific devices. This review comprehensively discusses the historical development of 3D printing and outlines the fundamental principles of the most widely used technologies in dentistry, including stereolithography (SLA), digital light processing (DLP), and liquid crystal display (LCD). These technologies enable the accurate and efficient fabrication of dental models, crowns, bridges, dentures, surgical guides, orthodontic appliances, and tissue engineering scaffolds. Current clinical applications are systematically summarized across major dental disciplines, including prosthodontics, orthodontics, oral and maxillofacial surgery, endodontics, periodontics, and pediatric dentistry. Despite existing challenges, such as limited long-term clinical data for certain materials, high initial equipment costs, and post-processing requirements, 3D printing offers substantial advantages in terms of customization, workflow efficiency, and clinical predictability of the final product. Future developments in advanced biomaterials, artificial intelligence-assisted workflows, bioprinting, and four-dimensional (4D) printing are expected to further expand the role of additive manufacturing in personalized and regenerative dentistry. Full article
(This article belongs to the Special Issue Advanced Polymers for Dental Applications)
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20 pages, 1983 KB  
Review
The Emerging Role of Hyaluronic Acid as a Multifunctional Regenerative Agent in Periodontal Healing
by Andrei-Mario Bădărău-Șuster, Amelia Tero-Vescan and Mark Slevin
Gels 2026, 12(3), 205; https://doi.org/10.3390/gels12030205 - 28 Feb 2026
Cited by 1 | Viewed by 1358
Abstract
Periodontitis is a multifactorial inflammatory disease characterized by dysbiotic microbial communities and progressive destruction of the supporting periodontal tissues, ultimately leading to alveolar bone loss. Achieving predictable periodontal regeneration remains a major clinical challenge because of the complex interplay between inflammation, microbial burden, [...] Read more.
Periodontitis is a multifactorial inflammatory disease characterized by dysbiotic microbial communities and progressive destruction of the supporting periodontal tissues, ultimately leading to alveolar bone loss. Achieving predictable periodontal regeneration remains a major clinical challenge because of the complex interplay between inflammation, microbial burden, and tissue remodeling. In this context, hyaluronic acid (HA), a naturally occurring component of the extracellular matrix (ECM), has gained increasing attention as a bioactive adjunct in periodontal therapy. This narrative review aims to describe current evidence regarding the biological properties, molecular mechanisms, and clinical applications of HA in periodontal therapy, with a particular focus on its immunomodulatory, antimicrobial, and regenerative potential. Available data indicate that HA exerts molecular weight–dependent effects, ranging from anti-inflammatory and extracellular matrix–stabilizing actions to osteogenic and immunostimulatory responses. Clinically, HA has been investigated as an adjunct in both nonsurgical and surgical periodontal therapies, as well as in minimally invasive regenerative approaches, as it has favorable effects on inflammation control, soft tissue healing, and clinical attachment gain. Recent advances in materials science have further expanded the role of HA through the development of engineered hydrogels and hybrid delivery systems incorporating nanoparticles, bioactive glass, growth factors, or antimicrobial agents, which have demonstrated promising osteogenic and antibacterial outcomes in preclinical models. However, the interpretation of existing evidence is limited by heterogeneity in HA formulations, short follow-up periods, and inconsistent reporting of periodontal defect morphology. Future research should focus on standardized, well-designed preclinical and clinical studies integrating histological, radiographic, immunological, and microbiological assessments to distinguish true periodontal regeneration from repair and to optimize HA-based strategies tailored to specific defect configurations. Full article
(This article belongs to the Special Issue Recent Advances in Hydrogels for Tissue Engineering Applications)
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32 pages, 1333 KB  
Review
Safety Assessment of Extracellular Vesicle-Based Therapy in Regenerative Dentistry
by Bing-Huan Chuah, Jia-Xian Law, Xin-Fang Leong, Kok-Lun Pang, Yan-Rou Farm, Masfueh Razali and Sook-Luan Ng
Int. J. Mol. Sci. 2026, 27(2), 798; https://doi.org/10.3390/ijms27020798 - 13 Jan 2026
Cited by 6 | Viewed by 1123
Abstract
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, [...] Read more.
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
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21 pages, 1716 KB  
Review
Phage Therapy: A Promising Approach in the Management of Periodontal Disease
by Paulo Juiz, Matheus Porto, David Moreira, Davi Amor and Eron Andrade
Drugs Drug Candidates 2026, 5(1), 6; https://doi.org/10.3390/ddc5010006 - 8 Jan 2026
Viewed by 1493
Abstract
Background/Objectives: Periodontal disease is a condition marked by the destruction of tooth-supporting tissues, driven by an exaggerated immune response to an unbalanced dental biofilm. Conventional treatments struggle due to antimicrobial resistance and the biofilm’s protective extracellular matrix. This study evaluates the potential of [...] Read more.
Background/Objectives: Periodontal disease is a condition marked by the destruction of tooth-supporting tissues, driven by an exaggerated immune response to an unbalanced dental biofilm. Conventional treatments struggle due to antimicrobial resistance and the biofilm’s protective extracellular matrix. This study evaluates the potential of bacteriophages as an innovative strategy for managing periodontal disease. Methods: This research employed a qualitative approach using Discursive Textual Analysis, with IRAMUTEQ version 0.8 alpha 7 (Interface de R pour les Analyses Multidimensionnelles de Textes et de Questionnaires) software. The search was conducted in the Orbit Intelligence and PubMed databases, for patents and scholarly articles, respectively. The textual data underwent Descending Hierarchical Classification, Correspondence Factor Analysis, and Similarity Analysis to identify core themes and relationships between words. Results: The analysis revealed an increase in research and patent filings concerning phage therapy for periodontal disease since 2017, emphasizing its market potential. The primary centers for intellectual property activity were identified as China and the United States. The study identified five focus areas: Genomic/Structural Characterization, Patent Formulations, Etiology, Therapeutic Efficacy, and Ecology/Phage Interactions. Lytic phages were shown to be effective against prominent pathogens such as Fusobacterium nucleatum and Enterococcus faecalis. Conversely, the lysogenic phages poses a potential risk, as they may transfer resistance and virulence factors, enhancing pathogenicity. Conclusions: Phage therapy is a promising approach to address antimicrobial resistance and biofilm challenges in periodontitis management. Key challenges include the need for the clinical validation of formulations and stable delivery systems for the subgingival area. Future strategies, such as phage genetic engineering and data-driven cocktail design, are crucial for enhancing efficacy and overcoming regulatory hurdles. Full article
(This article belongs to the Special Issue Microbes and Medicines)
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20 pages, 1443 KB  
Review
Cannabinoid Signaling and Autophagy in Oral Disease: Molecular Mechanisms and Therapeutic Implications
by Undral Munkhsaikhan, Md Ataur Rahman, Alivia Shasteen, Karima Ait-Aissa, Amal M. Sahyoun, Rajat Das Gupta, Modar Kassan, Ehsanul Hoque Apu and Ammaar H. Abidi
Int. J. Mol. Sci. 2026, 27(1), 525; https://doi.org/10.3390/ijms27010525 - 4 Jan 2026
Cited by 1 | Viewed by 1883
Abstract
Autophagy is a well-preserved biological mechanism that is essential for sustaining homeostasis by degradation and recycling damaged organelles, misfolded proteins, and other cytoplasmic detritus. Cannabinoid signaling has emerged as a prospective regulator of diverse cellular functions, including immunological modulation, oxidative stress response, apoptosis, [...] Read more.
Autophagy is a well-preserved biological mechanism that is essential for sustaining homeostasis by degradation and recycling damaged organelles, misfolded proteins, and other cytoplasmic detritus. Cannabinoid signaling has emerged as a prospective regulator of diverse cellular functions, including immunological modulation, oxidative stress response, apoptosis, and autophagy. Dysregulation of autophagy contributes to pathogenesis and treatment resistance of several oral diseases, including oral squamous cell carcinoma (OSCC), periodontitis, and gingival inflammation. This review delineates the molecular crosstalk between cannabinoid receptor type I (CB1) and type II (CB2) activation and autophagic pathways across oral tissues. Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), modulate key regulators like mTOR, AMPK, and Beclin-1, thereby influencing autophagic flux, inflammation, and apoptosis. Experimental studies indicate that cannabinoids inhibit the PI3K/AKT/mTOR pathway, promote reactive oxygen species (ROS)-induced autophagy, and modulate cytokine secretion, mechanisms that underline their dual anti-inflammatory and anti-cancer capabilities. In addition, cannabinoid-induced autophagy has been shown to enhance stem cell survival and differentiation, offering promise for dental pulp regeneration. Despite these promising prospects, several challenges remain, including receptor selectivity, dose-dependent variability, limited oral bioavailability, and ongoing regulatory constraints. A deeper understanding of the context-dependent regulation of autophagy by cannabinoid signaling could pave the way for innovative therapeutic interventions in dentistry. Tailored cannabinoid-based formulations, engineered for receptor specificity, tissue selectivity, and optimized delivery, hold significant potential to revolutionize oral healthcare by modulating autophagy-related molecular pathways involved in disease resolution and tissue regeneration. Full article
(This article belongs to the Section Molecular Oncology)
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31 pages, 22151 KB  
Article
Calcium-Enriched Magnetic Core–Shell Mesoporous Nanoparticles for Potential Application in Bone Regeneration
by Despoina Kordonidou, Georgia K. Pouroutzidou, Nikoletta Florini, Ioannis Tsamesidis, Konstantina Kazeli, Dimitrios Gkiliopoulos, George Vourlias, Makis Angelakeris, Philomela Komninou, Panos Patsalas and Eleana Kontonasaki
Nanomaterials 2025, 15(24), 1904; https://doi.org/10.3390/nano15241904 - 18 Dec 2025
Cited by 1 | Viewed by 1176
Abstract
Magnetite (Fe3O4) nanoparticles are biocompatible, non-toxic, and easily functionalized. Coating them with mesoporous silica (mSiO2) offers high surface area, pore volume, and tunable surface chemistry for drug loading. In this study, Fe3O4 magnetic nanoparticles [...] Read more.
Magnetite (Fe3O4) nanoparticles are biocompatible, non-toxic, and easily functionalized. Coating them with mesoporous silica (mSiO2) offers high surface area, pore volume, and tunable surface chemistry for drug loading. In this study, Fe3O4 magnetic nanoparticles were synthesized and coated with mSiO2 shells enriched with calcium ions (Ca2+), aiming to enhance bioactivity for bone regeneration and tissue engineering. Different synthesis routes were tested to optimize shell formation Their characterization confirmed the presence of a crystalline Fe3O4 core with partial conversion to maghemite (Fe2O3) post-coating. The silica shell was mostly amorphous and the optimized samples exhibited mesoporous structure (type IVb). Calcium incorporation slightly altered the magnetic properties without significantly affecting core crystallinity or particle size (11.68–13.56 nm). VSM analysis displayed symmetric hysteresis loops and decreased saturation magnetization after coating and Ca2+ addition. TEM showed spherical morphology with some agglomeration. MTT assays confirmed overall non-toxicity, except for mild cytotoxicity at high concentrations in the Ca2+-enriched sample synthesized by a modified Stöber method. Their capacity to induce human periodontal ligament cell osteogenic differentiation, further supports the potential of Fe3O4/mSiO2/Ca2+ core–shell nanoparticles as promising candidates for bone-related biomedical applications due to their favorable magnetic, structural, and biological properties. Full article
(This article belongs to the Section Nanocomposite Materials)
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28 pages, 2932 KB  
Review
Chitosan Sponges as Next-Generation Biomaterials for Dental Tissue Engineering and Periodontal Regeneration
by Magdalena Paczkowska-Walendowska, Maciej Kulawik, Jakub Kwiatek, Dimitrios Bikiaris and Judyta Cielecka-Piontek
Pharmaceutics 2025, 17(12), 1622; https://doi.org/10.3390/pharmaceutics17121622 - 17 Dec 2025
Cited by 3 | Viewed by 1521
Abstract
Chitosan, a naturally derived polysaccharide obtained by chitin deacetylation, has attracted considerable attention in dentistry as a multifunctional biomaterial owing to its excellent biocompatibility, biodegradability, and tunable physicochemical properties. This narrative review provides an up-to-date overview of the use of chitosan-based sponges in [...] Read more.
Chitosan, a naturally derived polysaccharide obtained by chitin deacetylation, has attracted considerable attention in dentistry as a multifunctional biomaterial owing to its excellent biocompatibility, biodegradability, and tunable physicochemical properties. This narrative review provides an up-to-date overview of the use of chitosan-based sponges in dental tissue engineering, bone regeneration, post-extraction wound management, and periodontal therapy. Chitosan sponges, characterized by high porosity, flexibility, and superior absorbency, serve as effective wound dressings, drug delivery carriers, and scaffolds that promote cell proliferation and tissue regeneration. Their intrinsic antibacterial, antifungal, hemostatic, and immunomodulatory properties further enhance their therapeutic value in managing complex oral conditions. In periodontal treatment, they enable localized drug delivery and support soft and hard tissue healing, while in post-extraction care, they aid hemostasis and reduce complications such as alveolar osteitis. Moreover, their osteoconductive and osteoinductive potential positions them as promising materials for alveolar bone repair and implantology. Chemical modification of chitosan and the incorporation of bioactive compounds allow customization of sponge formulations to meet specific clinical needs. Despite encouraging preclinical findings, challenges remain due to variability in chitosan sources, differences in the degree of deacetylation, and limited clinical validation. This review highlights the potential of chitosan sponges as innovative tools in regenerative dentistry and underscores the need for further standardization, mechanistic studies, and long-term clinical trials to ensure their safe and effective translation into dental practice. Moreover, the broad clinical applications of chitosan sponges beyond dentistry confirm their potential as a universal biomaterial platform in regenerative medicine. Full article
(This article belongs to the Special Issue Biomaterials for Oral and Dental Drug Delivery)
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23 pages, 648 KB  
Systematic Review
The Effectiveness and Safety of Stem Cell-Based Tissue Engineering in the Regeneration of Periodontal Bone Lesions: A Systematic Review
by Marouan Fanid, Ana Sofia Vinhas, Cátia Reis, Marta Relvas, Rosana Costa and Cristina Cabral
Clin. Pract. 2025, 15(12), 222; https://doi.org/10.3390/clinpract15120222 - 26 Nov 2025
Viewed by 2494
Abstract
Background/Objectives: Periodontal diseases are highly prevalent worldwide, causing progressive destruction of the alveolar bone and eventual tooth loss when not treated. Despite advances in conventional periodontal therapies, complete tissue regeneration remains limited. This review aims to evaluate the efficacy, safety, and clinical relevance [...] Read more.
Background/Objectives: Periodontal diseases are highly prevalent worldwide, causing progressive destruction of the alveolar bone and eventual tooth loss when not treated. Despite advances in conventional periodontal therapies, complete tissue regeneration remains limited. This review aims to evaluate the efficacy, safety, and clinical relevance of stem cell-based tissue engineering approaches for regeneration of periodontal bone lesions. Methods: Following PRISMA guidelines, a systematic search was conducted across multiple databases, resulting in the inclusion of 17 studies in humans that met predefined PICO criteria. The study protocol was registered on PROSPERO (CRD420251229271). These studies assessed various stem cell sources, including dental and bone marrow-derived cells among others, both on their own and in combination with scaffolds or growth factors. Results: Most studies reported favorable outcomes in terms of clinical attachment gain, radiographic bone fill, probing depth reduction, and implant stability. No major adverse effects were noted, indicating good safety. However, results varied based on cell type, culture protocols, and defect characteristics. Conclusions: Stem cell therapy shows strong potential for periodontal regeneration, with outcomes that may potentially surpass those of conventional methods in selected cases. Further standardization, cost reduction, and long-term clinical trials are essential to confirm these findings and support their integration into daily dental practice. Full article
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53 pages, 1288 KB  
Review
Recent Advances in Periodontal Regenerative Medicine: A Focus on the Role of Mechanical Stimulation
by Lidiia Grinchevskaia, Daria Revokatova, Mohammad Hadi Norahan, Alexey Senkovenko, Frederico David Alencar de Sena Pereira, Nastasia Kosheleva, Anastasia Shpichka and Peter Timashev
Biomedicines 2025, 13(11), 2839; https://doi.org/10.3390/biomedicines13112839 - 20 Nov 2025
Cited by 4 | Viewed by 5756
Abstract
Periodontitis is a prevalent chronic inflammatory disease that leads to the progressive destruction of periodontal tissues and remains the primary cause of tooth loss worldwide. Despite advances in regenerative approaches—including stem cell therapy, scaffold-based tissue engineering, and guided tissue regeneration—the complete and functional [...] Read more.
Periodontitis is a prevalent chronic inflammatory disease that leads to the progressive destruction of periodontal tissues and remains the primary cause of tooth loss worldwide. Despite advances in regenerative approaches—including stem cell therapy, scaffold-based tissue engineering, and guided tissue regeneration—the complete and functional restoration of the periodontal ligament remains a major clinical challenge. Stem-cell-based therapies and advanced biomaterials have emerged as promising strategies in regenerative medicine, offering potential for restoring periodontal structure and function. Among cells, periodontal-ligament-derived stem cells (PDLSCs) show exceptional regenerative potential due to their ability to differentiate into cementoblasts, osteoblasts, and other cell types essential for periodontal repair. In recent years, a variety of biomaterials with distinct specifications and properties have been utilized to repair periodontal damage. In addition to the inherent properties of biomaterials, the morphology and structural characteristics of these materials as bioequivalents for periodontal regeneration are also critical considerations. Furthermore, recent studies emphasize that mechanical stimulation plays a considerable role in directing stem cell differentiation, gene expression, matrix organization, and modulating inflammatory responses in periodontal regeneration. Canonical parameter ranges for systematic analysis indicate that cyclic stretch strain of 1–20% at 0.1–0.5 Hz (6–30 cycles/min) typically increases the expression of osteogenic markers (RUNX2, ALP, OCN) and matrix components (Col1) in PDLSCs. Conversely, higher values (>15%) often bias the response toward inflammatory pathways (IL-6, PGE2). Static compression above 2 g/cm2 consistently stimulates the secretion of pro-inflammatory cytokines (IL-6, IL-8) and alters the RANKL/OPG balance in favor of osteoclastogenesis. Significant heterogeneity in response across studies will be analyzed by examining key methodological variables, including specific loading regimens (duration, frequency patterns) and culture conditions (e.g., serum/osteogenic supplements), which critically modulate mechanotransduction outcomes. This review summarizes current progress in periodontal regenerative medicine, emphasizing cellular and biomaterial considerations, as well as biofabrication techniques, with a particular focus on the influence of mechanical forces on PDLSCs. We discuss cellular responses to mechanical stimuli, including changes in gene expression, cytoskeletal organization, proliferation, and differentiation. Combining biological knowledge with advances in bioprinting and the study of mechanobiology, we finally discuss promising opportunities for improving periodontal regeneration that can be applied in the future in clinical practice. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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16 pages, 458 KB  
Review
Leveraging Dental Biotechnology for Population Oral Health: Innovations in Prevention, Diagnosis, and Treatment
by Omer Faruk Sonmez, Thuto Serufe Makara and Raman Bedi
Int. J. Mol. Sci. 2025, 26(22), 11188; https://doi.org/10.3390/ijms262211188 - 19 Nov 2025
Cited by 2 | Viewed by 2055
Abstract
Biotechnology is reshaping dental public health by providing new tools for prevention, diagnosis, and treatment of oral diseases at scale. Salivary biomarkers enable non-invasive, early detection of caries, periodontitis, and oral cancer. Tissue engineering and regenerative approaches, driven by stem cell signaling and [...] Read more.
Biotechnology is reshaping dental public health by providing new tools for prevention, diagnosis, and treatment of oral diseases at scale. Salivary biomarkers enable non-invasive, early detection of caries, periodontitis, and oral cancer. Tissue engineering and regenerative approaches, driven by stem cell signaling and bioactive scaffolds, offer biologically integrated repair. Genomic discoveries now allow polygenic risk profiling to complement social determinants in identifying vulnerable groups, while novel biomaterials, probiotics, and vaccine research expand options for sustainable caries prevention. These innovations are underpinned by molecular mechanisms such as inflammatory signaling, stem cell differentiation pathways, and antimicrobial activity. Their translation into public health practice requires attention to affordability, regulation, equity, and workforce integration. Harnessed effectively, biotechnology can help shift oral health systems toward more preventive and equitable models of care. Full article
(This article belongs to the Special Issue Application of Biotechnology to Dental Treatment)
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36 pages, 2754 KB  
Review
Bioengineering of Periodontal Tissues: Cell Therapy and Biomaterials Application
by Mohammad Hadi Norahan, Sudesh Sivarasu, Alexey Fayzullin, Chibuike Mbanefo, Polina Bikmulina, Igor Ashurko, Iana Khristidis and Peter Timashev
Bioengineering 2025, 12(11), 1213; https://doi.org/10.3390/bioengineering12111213 - 6 Nov 2025
Cited by 4 | Viewed by 3592
Abstract
Periodontal regeneration remains one of the most demanding challenges in oral bioengineering due to the structural complexity of the periodontium and the inflammatory microenvironment accompanying disease. Conventional surgical and pharmacological therapies often fail to achieve full restoration of bone, ligament and cementum, prompting [...] Read more.
Periodontal regeneration remains one of the most demanding challenges in oral bioengineering due to the structural complexity of the periodontium and the inflammatory microenvironment accompanying disease. Conventional surgical and pharmacological therapies often fail to achieve full restoration of bone, ligament and cementum, prompting the development of cell-based and biomaterial-assisted approaches. This review summarizes current advances in cellular technologies for periodontal regeneration, emphasizing the biological rationale, material design and delivery methods shaping next-generation treatments. We discuss stem-cell-based strategies employing periodontal ligament, dental pulp and mesenchymal stem cells, their paracrine and immunomodulatory roles, and how their therapeutic potential is enhanced through integration into engineered scaffolds. Recent progress in hydrogel systems, microspheres, decellularized matrices and 3D bioprinting is analyzed, highlighting how structural cues, bioactive nanoparticles and gene-modified cells enable multi-tissue regeneration. Emerging delivery and biofabrication techniques, from manual seeding to automated and in situ printing, are reviewed as key determinants of clinical translation. The convergence of bioprinting precision, immune-responsive biomaterials and personalized cellular constructs positions periodontal bioengineering as a rapidly maturing field with strong prospects for functional restoration of diseased oral tissues. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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