Soyoung Hwang, Seunghye Park, Jin Woo Lee, Mira Park, Le Anh Nguyet, Yongsung Hwang, Keunsun Ahn, Hyun-Young Shin, Kuk Hui Son
Plant-derived polynucleotides (PNs) have emerged as promising regenerative biomolecules; however, their mechanisms remain less defined than those of salmon-derived polydeoxyribonucleotides (S-PDRNs). Here, we extracted polynucleotides from Paeonia lactiflora callus (PL-PN) and evaluated their biological effects on human dermal fibroblasts. PL-PN treatment increased cell viability and pro-collagen I α1 secretion. PL-PN enhanced adenosine A2A receptor expression and activated the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, accompanied by increased Cyclin D1 levels, retinoblastoma protein (Rb) phosphorylation, and nuclear proliferating cell nuclear antigen (PCNA) levels, indicating an accelerated G1/S transition. PL-PN also significantly reduced nuclear NF-κB localization and downregulated MMP1, MMP3, MMP9, and MMP13, suggesting attenuation of inflammatory and catabolic signaling. Furthermore, PL-PN increased TGF-β maturation, Smad2/3 phosphorylation, and the transcription of COL1A1, COL3A1, and elastin, resulting in enhanced collagen and elastin deposition. These effects are comparable to those of S-PDRN. Although the pathway specificity and in vivo relevance require further studies, our findings provide evidence that PL-PN promotes extracellular matrix regeneration via coordinated proliferative, anabolic, and anti-inflammatory actions. Thus, PL-PN represents a potential sustainable plant-based alternative to S-PDRN for dermatological regeneration.
{"title":"<i>Paeonia lactiflora</i> Callus-Derived Polynucleotides Enhance Collagen Accumulation in Human Dermal Fibroblasts.","authors":"Soyoung Hwang, Seunghye Park, Jin Woo Lee, Mira Park, Le Anh Nguyet, Yongsung Hwang, Keunsun Ahn, Hyun-Young Shin, Kuk Hui Son","doi":"10.3390/jfb17010056","DOIUrl":"10.3390/jfb17010056","url":null,"abstract":"<p><p>Plant-derived polynucleotides (PNs) have emerged as promising regenerative biomolecules; however, their mechanisms remain less defined than those of salmon-derived polydeoxyribonucleotides (S-PDRNs). Here, we extracted polynucleotides from <i>Paeonia lactiflora</i> callus (PL-PN) and evaluated their biological effects on human dermal fibroblasts. PL-PN treatment increased cell viability and pro-collagen I α1 secretion. PL-PN enhanced adenosine A2A receptor expression and activated the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, accompanied by increased Cyclin D1 levels, retinoblastoma protein (Rb) phosphorylation, and nuclear proliferating cell nuclear antigen (PCNA) levels, indicating an accelerated G1/S transition. PL-PN also significantly reduced nuclear NF-κB localization and downregulated MMP1, MMP3, MMP9, and MMP13, suggesting attenuation of inflammatory and catabolic signaling. Furthermore, PL-PN increased TGF-β maturation, Smad2/3 phosphorylation, and the transcription of COL1A1, COL3A1, and elastin, resulting in enhanced collagen and elastin deposition. These effects are comparable to those of S-PDRN. Although the pathway specificity and in vivo relevance require further studies, our findings provide evidence that PL-PN promotes extracellular matrix regeneration via coordinated proliferative, anabolic, and anti-inflammatory actions. Thus, PL-PN represents a potential sustainable plant-based alternative to S-PDRN for dermatological regeneration.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12842499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted considerable interest. The primary advantage of this material is the level of structural control it affords. The fibre orientation, porosity, and overall microarchitecture can be adjusted to replicate the organisation and mechanical behaviour of the natural membrane. A range of biocompatible polymers-among them silk fibroin, poly(ε-caprolactone), poly(lactic acid), and poly(vinyl alcohol) and their composites-provide options for tuning stiffness, degradation rates, and interactions with cells, making them suitable building blocks for TM repair constructs. This review provides a comprehensive overview of contemporary fabrication methodologies, namely electrospinning, additive manufacturing, melt electrowriting, and hybrid strategies. In addition, it offers a detailed discussion of the evaluation procedures employed for these scaffolds and discusses how scaffold structure affects later performance. Mechanical testing, microstructural imaging, and in vitro biocompatibility assays help to determine how closely a construct can approach the performance of the native tissue. Bringing these elements together may support the gradual translation of fibre-based TM scaffolds into clinical practice.
{"title":"Fibrous Biomaterial Scaffold for Tympanic Membrane Repair: Microarchitectural Engineering and Structure Function Performance.","authors":"Lea Jiang, Chokri Cherif, Michael Wöltje","doi":"10.3390/jfb17010053","DOIUrl":"10.3390/jfb17010053","url":null,"abstract":"<p><p>Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted considerable interest. The primary advantage of this material is the level of structural control it affords. The fibre orientation, porosity, and overall microarchitecture can be adjusted to replicate the organisation and mechanical behaviour of the natural membrane. A range of biocompatible polymers-among them silk fibroin, poly(ε-caprolactone), poly(lactic acid), and poly(vinyl alcohol) and their composites-provide options for tuning stiffness, degradation rates, and interactions with cells, making them suitable building blocks for TM repair constructs. This review provides a comprehensive overview of contemporary fabrication methodologies, namely electrospinning, additive manufacturing, melt electrowriting, and hybrid strategies. In addition, it offers a detailed discussion of the evaluation procedures employed for these scaffolds and discusses how scaffold structure affects later performance. Mechanical testing, microstructural imaging, and in vitro biocompatibility assays help to determine how closely a construct can approach the performance of the native tissue. Bringing these elements together may support the gradual translation of fibre-based TM scaffolds into clinical practice.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hydraulic calcium silicate cements (HCSCs) are contemporary materials in vital pulp therapy (VPT) and regenerative endodontic therapy (RET) due to their favorable effects on pulpal and periodontal cells, including cell differentiation and hard tissue formation. Recent studies also indicated the involvement of several S100A proteins in inflammatory, differentiation, and mineralization processes of the pulp. The aim of the present study was to investigate the effects of HCSCs on S100A gene expression in human dental pulp stem cells (hDPSCs). Human DPSCs were isolated and characterized by multi-lineage stem-cell markers and differentiation protocols. In stimulation experiments hDPSCs were exposed to ProRoot®MTA, Biodentine®, IL-1β, and dexamethasone. Cell viability was determined by XTT assay. IL-6 and IL-8 mRNA expression was measured to analyze proinflammatory response. In addition, odontogenic differentiation and biomineralization assays were conducted (DSPP- and ALP-mRNA expression, ALP activity, and Alizarin Red staining). Differential expression of 13 S100A genes was examined using qPCR. Low concentrations of HCSCs enhanced the proliferation of hDPSCs, whereas higher concentrations exhibited cytotoxic effects. HCSCs induced a pro-inflammatory response and led to odontogenic differentiation and biomineralization. This was accompanied by significant alterations in the expression levels of various S100A genes. ProRoot®MTA and Biodentine® significantly affect the expression of several S100A genes in hDPSCs, supporting their role in inflammation, differentiation, and mineralization. These findings indicate a link between the effects of HCSCs on human pulp cells during VPT or RET and S100A proteins.
{"title":"Differential Expression of S100A Genes in hDPSCs Following Stimulation with Two Hydraulic Calcium Silicate Cements: A Laboratory Investigation.","authors":"Holger Jungbluth, Diana Lalaouni, Jochen Winter, Søren Jepsen, Dominik Kraus","doi":"10.3390/jfb17010055","DOIUrl":"10.3390/jfb17010055","url":null,"abstract":"<p><p>Hydraulic calcium silicate cements (HCSCs) are contemporary materials in vital pulp therapy (VPT) and regenerative endodontic therapy (RET) due to their favorable effects on pulpal and periodontal cells, including cell differentiation and hard tissue formation. Recent studies also indicated the involvement of several S100A proteins in inflammatory, differentiation, and mineralization processes of the pulp. The aim of the present study was to investigate the effects of HCSCs on S100A gene expression in human dental pulp stem cells (hDPSCs). Human DPSCs were isolated and characterized by multi-lineage stem-cell markers and differentiation protocols. In stimulation experiments hDPSCs were exposed to ProRoot<sup>®</sup>MTA, Biodentine<sup>®</sup>, IL-1β, and dexamethasone. Cell viability was determined by XTT assay. IL-6 and IL-8 mRNA expression was measured to analyze proinflammatory response. In addition, odontogenic differentiation and biomineralization assays were conducted (DSPP- and ALP-mRNA expression, ALP activity, and Alizarin Red staining). Differential expression of 13 S100A genes was examined using qPCR. Low concentrations of HCSCs enhanced the proliferation of hDPSCs, whereas higher concentrations exhibited cytotoxic effects. HCSCs induced a pro-inflammatory response and led to odontogenic differentiation and biomineralization. This was accompanied by significant alterations in the expression levels of various S100A genes. ProRoot<sup>®</sup>MTA and Biodentine<sup>®</sup> significantly affect the expression of several S100A genes in hDPSCs, supporting their role in inflammation, differentiation, and mineralization. These findings indicate a link between the effects of HCSCs on human pulp cells during VPT or RET and S100A proteins.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Przemysław Wróblewski, Michał Wieteska, Mateusz Midura, Grzegorz Domański, Damian Wanta, Wojciech Obrębski, Tomasz Płociński, Ewa Piątkowska-Janko, Kamil Lipiński, Mikhail Ivanenko, Mateusz Orzechowski, Waldemar T Smolik, Piotr Bogorodzki
The aim of the article was to analyze the potential simultaneous use of magnetic nanoparticles as contrast agents in MRI imaging and for magnetic hyperthermia. The study proposed characterizing the nanoparticles using various measurement methods in order to investigate the relationships between different properties. The first stage involved measuring images of nanoparticle samples using scanning transmission electron microscopy (TEM) and dynamic light scattering (DLS). The diameter distribution of nanoparticles was determined based on image segmentation. The next step involved measuring relaxation properties of nanoparticles in low and high magnetic fields. The research was carried out for nanoparticle solutions of various concentrations and properties. The last step was measuring calorimetric properties of nanoparticles as a thermal source under alternating magnetic field excitation conditions. The range of nanoparticle diameters (20-25 nm) for which maximum losses occur in an alternating magnetic field corresponds to the diameter range in which the maximum r2 relaxivity is observed.
{"title":"Analysis of the Feasibility of Concurrent Application of Magnetic Nanoparticles as MRI Contrast Agents and for Magnetic Hyperthermia.","authors":"Przemysław Wróblewski, Michał Wieteska, Mateusz Midura, Grzegorz Domański, Damian Wanta, Wojciech Obrębski, Tomasz Płociński, Ewa Piątkowska-Janko, Kamil Lipiński, Mikhail Ivanenko, Mateusz Orzechowski, Waldemar T Smolik, Piotr Bogorodzki","doi":"10.3390/jfb17010054","DOIUrl":"10.3390/jfb17010054","url":null,"abstract":"<p><p>The aim of the article was to analyze the potential simultaneous use of magnetic nanoparticles as contrast agents in MRI imaging and for magnetic hyperthermia. The study proposed characterizing the nanoparticles using various measurement methods in order to investigate the relationships between different properties. The first stage involved measuring images of nanoparticle samples using scanning transmission electron microscopy (TEM) and dynamic light scattering (DLS). The diameter distribution of nanoparticles was determined based on image segmentation. The next step involved measuring relaxation properties of nanoparticles in low and high magnetic fields. The research was carried out for nanoparticle solutions of various concentrations and properties. The last step was measuring calorimetric properties of nanoparticles as a thermal source under alternating magnetic field excitation conditions. The range of nanoparticle diameters (20-25 nm) for which maximum losses occur in an alternating magnetic field corresponds to the diameter range in which the maximum r<sub>2</sub> relaxivity is observed.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cristian Scheau, Andreea Cristiana Didilescu, Constantin Caruntu
Regenerative medicine stands at a crossroad between biology and materials science, where functional biomaterials are expected to interact with living tissues, guide repair, and restore functionality [...].
{"title":"From Scaffolds to Complex Systems: Functional Biomaterials in Regenerative Medicine.","authors":"Cristian Scheau, Andreea Cristiana Didilescu, Constantin Caruntu","doi":"10.3390/jfb17010051","DOIUrl":"10.3390/jfb17010051","url":null,"abstract":"<p><p>Regenerative medicine stands at a crossroad between biology and materials science, where functional biomaterials are expected to interact with living tissues, guide repair, and restore functionality [...].</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faye Fouladgar, Robert Powell, Emily Carney, Andrea Escobar Martinez, Amir Jafari, Neda Habibi
Mechanical stimulation critically regulates mesenchymal stem cell (MSC) differentiation, yet its effects in three-dimensional (3D) environments remain poorly defined. Here, we developed a custom dynamic stretcher integrating poly(dimethylsiloxane) (PDMS) chambers to apply cyclic strain to human MSCs encapsulated in Fmoc-diphenylalanine (Fmoc-FF) peptide hydrogels-a fully synthetic, tunable extracellular matrix mimic. Finite element modeling verified uniform strain transmission across the hydrogel. Dynamic stretching at 0.5 Hz and 10% strain induced pronounced cytoskeletal alignment, enhanced actin stress fiber formation (coherency index ≈ 0.85), and significantly increased proliferation compared to static or high-frequency (2.5 Hz, 1%) conditions (coherency index ≈ 0.6). Quantitative image analysis confirmed strain-dependent increases in coherency index and F-actin intensity, indicating enhanced mechanotransductive remodeling. Biochemical assays and qRT-PCR revealed 2-3-fold upregulation of osteogenic markers-RUNX2, ALP, COL1A1, OSX, BMP, ON, and IBSP-under optimal strain. These results demonstrate that low-frequency, high-strain mechanical loading in 3D peptide hydrogels activates RhoA/ROCK and YAP/TAZ pathways, driving osteogenic differentiation. The integrated experimental-computational approach provides a robust platform for studying mechanobiological regulation and advancing mechanically tunable biomaterials for bone tissue engineering.
{"title":"Biomechanical Stimulation of Mesenchymal Stem Cells in 3D Peptide Nanofibers for Bone Differentiation.","authors":"Faye Fouladgar, Robert Powell, Emily Carney, Andrea Escobar Martinez, Amir Jafari, Neda Habibi","doi":"10.3390/jfb17010052","DOIUrl":"10.3390/jfb17010052","url":null,"abstract":"<p><p>Mechanical stimulation critically regulates mesenchymal stem cell (MSC) differentiation, yet its effects in three-dimensional (3D) environments remain poorly defined. Here, we developed a custom dynamic stretcher integrating poly(dimethylsiloxane) (PDMS) chambers to apply cyclic strain to human MSCs encapsulated in Fmoc-diphenylalanine (Fmoc-FF) peptide hydrogels-a fully synthetic, tunable extracellular matrix mimic. Finite element modeling verified uniform strain transmission across the hydrogel. Dynamic stretching at 0.5 Hz and 10% strain induced pronounced cytoskeletal alignment, enhanced actin stress fiber formation (coherency index ≈ 0.85), and significantly increased proliferation compared to static or high-frequency (2.5 Hz, 1%) conditions (coherency index ≈ 0.6). Quantitative image analysis confirmed strain-dependent increases in coherency index and F-actin intensity, indicating enhanced mechanotransductive remodeling. Biochemical assays and qRT-PCR revealed 2-3-fold upregulation of osteogenic markers-<i>RUNX2</i>, <i>ALP</i>, <i>COL1A1</i>, <i>OSX</i>, <i>BMP</i>, <i>ON</i>, and <i>IBSP</i>-under optimal strain. These results demonstrate that low-frequency, high-strain mechanical loading in 3D peptide hydrogels activates RhoA/ROCK and YAP/TAZ pathways, driving osteogenic differentiation. The integrated experimental-computational approach provides a robust platform for studying mechanobiological regulation and advancing mechanically tunable biomaterials for bone tissue engineering.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leticia Martins Pereira, Marina Damasceno E Souza de Carvalho Chiari, Diego Mauro Carneiro Pereira, Regina Maria Puppin-Rontani, Fábio Dupart Nascimento
(1) Background: The synthetic eleven-amino acid peptide P11-4, derived from DMP-1, self-assembles into β-sheet tapes, ribbons, fibrils, and fibers that form a 3D matrix enriched with calcium-binding sites. This study investigated whether P11-4 modulates gene and protein expression or induces adverse metabolic alterations in odontoblast-like cells. (2) Methods: MDPC-23 cells were cultured under standard conditions and stimulated with different concentrations of P11-4, followed by assessments of cell viability using the MTT assay, proliferation and migration, cytoplasmic calcium kinetics, reactive oxygen species (ROS) production, osteogenic differentiation-related gene expression via PCR array, and expression of the pro-inflammatory cytokine interleukin-6 (IL-6) using confocal microscopy and flow cytometry. (3) Results: The MTT assay showed that P11-4 at 6.3, 12.6, and 25.2 µmol/L was non-cytotoxic and did not alter MDPC-23 cell proliferation or migration. Only the 25.2 µmol/L concentration induced a detectable Ca2+ influx and a slight increase in ROS. Among the 84 genes examined, P11-4 at 6.3 µmol/L upregulated 79 genes, including transcription factors, signaling molecules, and extracellular matrix-related proteins. Furthermore, P11-4 did not increase IL-6 expression under any condition tested. (4) Conclusion: P11-4 markedly modulates mineralization-associated gene regulation without causing metabolic damage in odontoblast-like cells.
{"title":"The Self-Assembling Peptide P<sub>11</sub>-4 Induces the Expression of Mineralization-Related Genes in Odontoblasts Independently of Metabolic Alterations.","authors":"Leticia Martins Pereira, Marina Damasceno E Souza de Carvalho Chiari, Diego Mauro Carneiro Pereira, Regina Maria Puppin-Rontani, Fábio Dupart Nascimento","doi":"10.3390/jfb17010050","DOIUrl":"10.3390/jfb17010050","url":null,"abstract":"<p><p>(1) Background: The synthetic eleven-amino acid peptide P<sub>11</sub>-4, derived from DMP-1, self-assembles into β-sheet tapes, ribbons, fibrils, and fibers that form a 3D matrix enriched with calcium-binding sites. This study investigated whether P<sub>11</sub>-4 modulates gene and protein expression or induces adverse metabolic alterations in odontoblast-like cells. (2) Methods: MDPC-23 cells were cultured under standard conditions and stimulated with different concentrations of P<sub>11</sub>-4, followed by assessments of cell viability using the MTT assay, proliferation and migration, cytoplasmic calcium kinetics, reactive oxygen species (ROS) production, osteogenic differentiation-related gene expression via PCR array, and expression of the pro-inflammatory cytokine interleukin-6 (IL-6) using confocal microscopy and flow cytometry. (3) Results: The MTT assay showed that P<sub>11</sub>-4 at 6.3, 12.6, and 25.2 µmol/L was non-cytotoxic and did not alter MDPC-23 cell proliferation or migration. Only the 25.2 µmol/L concentration induced a detectable Ca<sup>2+</sup> influx and a slight increase in ROS. Among the 84 genes examined, P<sub>11</sub>-4 at 6.3 µmol/L upregulated 79 genes, including transcription factors, signaling molecules, and extracellular matrix-related proteins. Furthermore, P<sub>11</sub>-4 did not increase IL-6 expression under any condition tested. (4) Conclusion: P<sub>11</sub>-4 markedly modulates mineralization-associated gene regulation without causing metabolic damage in odontoblast-like cells.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12842195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Little is known about the effects of orthodontic loading on dental implants used for orthodontic anchorage in patients with Stage IV periodontitis. This retrospective case-control study included 58 dental implants in 24 patients with treated Stage IV periodontitis. The dental implants were used for both chewing function and orthodontic anchorages. The outcome measures included peri-implant marginal bone loss and peri-implantitis. Pair t-test and Wilcoxon rank-sum test were used to analyze the impact of implants as orthodontic anchorage on marginal bone loss (MBL) and peri-implantitis. No implants were lost during the 17-year follow-up. There was no statistically significant difference in the MBL and incidence of peri-implantitis between implants used as orthodontic anchorage and non-anchorage controls. (p > 0.05). Poor oral hygiene (p = 0.05), one-piece implants (p = 0.05) and implants with a keratinized mucosa < 2 mm (p = 0.015) were associated with a higher risk of peri-implantitis. Results from the present long-term study indicated that dental implants could be successfully used as orthodontic anchorage in periodontal compromised patients.
{"title":"Dental Implants Used for Orthodontic Anchorage in Patients with Treated Stage IV Periodontitis: A Retrospective Case-Control Study.","authors":"Shing-Zeng Dung, I-Shiang Tzeng","doi":"10.3390/jfb17010049","DOIUrl":"10.3390/jfb17010049","url":null,"abstract":"<p><p>Little is known about the effects of orthodontic loading on dental implants used for orthodontic anchorage in patients with Stage IV periodontitis. This retrospective case-control study included 58 dental implants in 24 patients with treated Stage IV periodontitis. The dental implants were used for both chewing function and orthodontic anchorages. The outcome measures included peri-implant marginal bone loss and peri-implantitis. Pair <i>t</i>-test and Wilcoxon rank-sum test were used to analyze the impact of implants as orthodontic anchorage on marginal bone loss (MBL) and peri-implantitis. No implants were lost during the 17-year follow-up. There was no statistically significant difference in the MBL and incidence of peri-implantitis between implants used as orthodontic anchorage and non-anchorage controls. (<i>p</i> > 0.05). Poor oral hygiene (<i>p</i> = 0.05), one-piece implants (<i>p</i> = 0.05) and implants with a keratinized mucosa < 2 mm (<i>p</i> = 0.015) were associated with a higher risk of peri-implantitis. Results from the present long-term study indicated that dental implants could be successfully used as orthodontic anchorage in periodontal compromised patients.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María-Inmaculada Vidal-Montolío, José Luis Sanz, James Ghilotti, Sofía Folguera, Carmen Llena
Irrigation plays a crucial role in the success of root canal treatment; however, currently, no standardized irrigation protocols exist, particularly regarding the optimal sequence for smear layer removal. This systematic review aimed to determine which irrigation protocol achieves superior smear layer removal: traditional sequential irrigation with sodium hypochlorite (NaOCl) followed by ethylenediaminetetraacetic acid (EDTA), or irrigation with etidronic acid, either combined with NaOCl in continuous chelation or used as a final irrigant. Continuous chelation with etidronic acid may be clinically advantageous in daily practice, as it would facilitate workflow by using a single irrigating solution without compromising the efficacy of the irrigation process. A comprehensive electronic search was conducted in Medline, Embase, Cochrane, Scopus, and Web of Science, last updated in August 2025. In vitro studies were selected according to predefined PICO-based criteria. Two reviewers independently screened the studies and extracted data, with an inter-rater agreement of 0.92 using the Kappa index. Risk of bias was evaluated using a modified CONSORT checklist for in vitro studies on dental materials. The average item compliance of the included studies was 58%. The maximum score was 73% and the minimum was 47%. Twenty studies met the inclusion criteria. Etidronic acid used in continuous chelation showed equal or superior smear layer removal compared with sequential irrigation in nine of ten studies. Conversely, when used as a final irrigant, etidronic acid demonstrated inferior performance in more than half of the studies, particularly in the apical third. Based on the available evidence, etidronic acid in continuous chelation appears as effective as, or more effective than, traditional NaOCl-EDTA sequential irrigation.
灌洗在根管治疗的成功中起着至关重要的作用;然而,目前还没有标准化的灌溉方案,特别是关于去除涂抹层的最佳顺序。本系统综述旨在确定哪种灌溉方案能更好地去除涂抹层:传统的次氯酸钠(NaOCl)顺序灌溉,然后是乙二胺四乙酸(EDTA),或者用地替膦酸灌溉,要么与NaOCl连续螯合,要么作为最后的灌溉剂。与依地膦酸的持续螯合在日常实践中可能具有临床优势,因为它可以通过使用单一的冲洗溶液来简化工作流程,而不会影响冲洗过程的效果。对Medline、Embase、Cochrane、Scopus和Web of Science进行了全面的电子检索,最后一次更新是在2025年8月。根据预先确定的基于pico的标准选择体外研究。两名审稿人独立筛选研究并提取数据,使用Kappa指数,审稿人间一致性为0.92。使用改良的CONSORT清单评估牙科材料体外研究的偏倚风险。纳入研究的平均项目依从性为58%。最高分数为73%,最低分数为47%。20项研究符合纳入标准。在十项研究中,有九项研究表明,与连续冲洗相比,连续螯合中使用的Etidronic酸具有相同或更好的涂抹层去除效果。相反,当用作最后的冲洗剂时,在一半以上的研究中,特别是在根尖的三分之一中,伊地膦酸表现出较差的性能。根据现有证据,持续螯合的依地膦酸似乎与传统的NaOCl-EDTA序贯灌洗一样有效,甚至更有效。
{"title":"Efficacy of Etidronic Acid for Smear Layer Removal: A Systematic Review of In Vitro Studies.","authors":"María-Inmaculada Vidal-Montolío, José Luis Sanz, James Ghilotti, Sofía Folguera, Carmen Llena","doi":"10.3390/jfb17010048","DOIUrl":"10.3390/jfb17010048","url":null,"abstract":"<p><p>Irrigation plays a crucial role in the success of root canal treatment; however, currently, no standardized irrigation protocols exist, particularly regarding the optimal sequence for smear layer removal. This systematic review aimed to determine which irrigation protocol achieves superior smear layer removal: traditional sequential irrigation with sodium hypochlorite (NaOCl) followed by ethylenediaminetetraacetic acid (EDTA), or irrigation with etidronic acid, either combined with NaOCl in continuous chelation or used as a final irrigant. Continuous chelation with etidronic acid may be clinically advantageous in daily practice, as it would facilitate workflow by using a single irrigating solution without compromising the efficacy of the irrigation process. A comprehensive electronic search was conducted in Medline, Embase, Cochrane, Scopus, and Web of Science, last updated in August 2025. In vitro studies were selected according to predefined PICO-based criteria. Two reviewers independently screened the studies and extracted data, with an inter-rater agreement of 0.92 using the Kappa index. Risk of bias was evaluated using a modified CONSORT checklist for in vitro studies on dental materials. The average item compliance of the included studies was 58%. The maximum score was 73% and the minimum was 47%. Twenty studies met the inclusion criteria. Etidronic acid used in continuous chelation showed equal or superior smear layer removal compared with sequential irrigation in nine of ten studies. Conversely, when used as a final irrigant, etidronic acid demonstrated inferior performance in more than half of the studies, particularly in the apical third. Based on the available evidence, etidronic acid in continuous chelation appears as effective as, or more effective than, traditional NaOCl-EDTA sequential irrigation.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12842351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Ewa Kuc, Jacek Kotuła, Kamil Sybilski, Szymon Saternus, Jerzy Małachowski, Natalia Kuc, Grzegorz Hajduk, Joanna Lis, Beata Kawala, Michał Sarul, Magdalena Sulewska
Background: Adult patients with a thin buccal cortical plate and fragile periodontal phenotype are at high risk of dehiscence, fenestration and recession during transverse orthodontic expansion. Conventional mechanics often create a cervical compression-dominant environment that exceeds the adaptive capacity of the periodontal ligament (PDL)-bone complex. Objectives: This study proposes an integrative mechanobiological model in which a skeletal-anchorage-assisted loading protocol (Bone Protection System, BPS) transforms expansion into a tension-dominant regime that favours buccal phenotype preservation. Methods: Patient-specific finite element models were used to compare conventional expansion with a BPS-modified force system. Regional PDL stress patterns and crown/apex displacement vectors were analysed to distinguish tipping-dominant from translation-dominated mechanics. A pilot CBCT proof-of-concept (n = 1 thin-phenotype adult) with voxel-based registration quantified changes in maxillary and mandibular alveolar ridge width and buccal cortical plate thickness before and after BPS-assisted expansion. The mechanical findings were integrated with current evidence on compression- versus tension-driven inflammatory and osteogenic pathways in the PDL and cortical bone. Results: FEM demonstrated that conventional expansion concentrates high cervical compressive stress along the buccal PDL and cortical surface, accompanied by bending-like crown-root divergence. In contrast, the BPS protocol redirected forces to create a buccal tensile-favourable region and a more parallel crown-apex displacement pattern, indicative of translation-dominated movement. In the proof-of-concept (n = 1) CBCT case, BPS-assisted expansion was associated with preservation or increase of buccal ridge dimensions without radiographic signs of cortical breakdown. Conclusions: A tension-dominant orthodontic loading environment generated by a skeletal-anchorage-assisted force system may support buccal cortical preservation and vestibular phenotype reinforcement in thin-phenotype patients. The proposed mechanobiological model links these imaging and FEM findings to known molecular pathways of inflammation, angiogenesis and osteogenesis. It suggests a functional biomaterial-based strategy for widening the biological envelope of safe tooth movement.
{"title":"Tension-Dominant Orthodontic Loading and Buccal Periodontal Phenotype Preservation: An Integrative Mechanobiological Model Supported by FEM and a Proof-of-Concept CBCT.","authors":"Anna Ewa Kuc, Jacek Kotuła, Kamil Sybilski, Szymon Saternus, Jerzy Małachowski, Natalia Kuc, Grzegorz Hajduk, Joanna Lis, Beata Kawala, Michał Sarul, Magdalena Sulewska","doi":"10.3390/jfb17010047","DOIUrl":"10.3390/jfb17010047","url":null,"abstract":"<p><p><b>Background:</b> Adult patients with a thin buccal cortical plate and fragile periodontal phenotype are at high risk of dehiscence, fenestration and recession during transverse orthodontic expansion. Conventional mechanics often create a cervical compression-dominant environment that exceeds the adaptive capacity of the periodontal ligament (PDL)-bone complex. <b>Objectives:</b> This study proposes an integrative mechanobiological model in which a skeletal-anchorage-assisted loading protocol (Bone Protection System, BPS) transforms expansion into a tension-dominant regime that favours buccal phenotype preservation. <b>Methods:</b> Patient-specific finite element models were used to compare conventional expansion with a BPS-modified force system. Regional PDL stress patterns and crown/apex displacement vectors were analysed to distinguish tipping-dominant from translation-dominated mechanics. A pilot CBCT proof-of-concept (n = 1 thin-phenotype adult) with voxel-based registration quantified changes in maxillary and mandibular alveolar ridge width and buccal cortical plate thickness before and after BPS-assisted expansion. The mechanical findings were integrated with current evidence on compression- versus tension-driven inflammatory and osteogenic pathways in the PDL and cortical bone. <b>Results:</b> FEM demonstrated that conventional expansion concentrates high cervical compressive stress along the buccal PDL and cortical surface, accompanied by bending-like crown-root divergence. In contrast, the BPS protocol redirected forces to create a buccal tensile-favourable region and a more parallel crown-apex displacement pattern, indicative of translation-dominated movement. In the proof-of-concept (n = 1) CBCT case, BPS-assisted expansion was associated with preservation or increase of buccal ridge dimensions without radiographic signs of cortical breakdown. <b>Conclusions:</b> A tension-dominant orthodontic loading environment generated by a skeletal-anchorage-assisted force system may support buccal cortical preservation and vestibular phenotype reinforcement in thin-phenotype patients. The proposed mechanobiological model links these imaging and FEM findings to known molecular pathways of inflammation, angiogenesis and osteogenesis. It suggests a functional biomaterial-based strategy for widening the biological envelope of safe tooth movement.</p>","PeriodicalId":15767,"journal":{"name":"Journal of Functional Biomaterials","volume":"17 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12843214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}