Journal of Functional Biomaterials

17 pages, 3957 KB

Open AccessArticle

Evaluation of Antimicrobials Incorporated into Artificial Saliva: Analysis Against Candida albicans

by Camila Alves Carneiro, Fenelon Martinho Lima Pontes, Karin Hermana Neppelenbroek, Rodrigo França and Vinicius Carvalho Porto

J. Funct. Biomater. 2026, 17(2), 63; https://doi.org/10.3390/jfb17020063 - 27 Jan 2026

Abstract

Saliva is essential for maintaining oral health, and conditions like hyposalivation increase the risk of diseases. To address this, artificial saliva (AS) formulations incorporated with antimicrobials have been proposed. This study aimed to evaluate the antimicrobial activity and determine the minimum inhibitory concentration [...] Read more.

Saliva is essential for maintaining oral health, and conditions like hyposalivation increase the risk of diseases. To address this, artificial saliva (AS) formulations incorporated with antimicrobials have been proposed. This study aimed to evaluate the antimicrobial activity and determine the minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of AS formulations containing nystatin (Nys), chlorhexidine diacetate 98% (Chx), and silver nanoparticles (AgNp) against Candida albicans biofilm. The fungistatic and fungicidal properties of six groups (AS; AS + AgNp 2 mM; AS + AgNp 4 mM; AS + AgNp 6 mM; AS + Nys; AS + Chx) were assessed using the XTT colorimetric assay. Additionally, 35 denture base heat-polymerized acrylic resin specimens were prepared and treated with the antimicrobials, serving as substrates for C. albicans biofilm development over 3, 6, and 12 h. Biofilm growth was quantified by CFU/mL counting. All analyses were performed with a significance level of p < 0.05. Results demonstrated fungal load inhibition and a reduction in metabolic activity across all experimental groups (p < 0.05). Notably, AS + Nys, AS + Chx, and AS + AgNp 6 mM exhibited similar and significant inhibitory effects against C. albicans biofilm. Full article

(This article belongs to the Special Issue Surface Analyses, Physicochemical and Mechanical Properties of Dental Biomaterials (2nd Edition))

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19 pages, 2602 KB

Open AccessArticle

Laser-Enhanced Biomorphic Scaffolds Support Multipotent Stem Cell Differentiation and Angiogenesis for Vascularised Bone Regeneration

by Sandeep Kumar, Neelam Iqbal, Yahui Pan, Evangelos Daskalakis, Heather Elizabeth Owston, El Mostafa Raif, Payal Ganguly, Sarathkumar Loganathan, Peter V. Giannoudis and Animesh Jha

J. Funct. Biomater. 2026, 17(2), 62; https://doi.org/10.3390/jfb17020062 - 26 Jan 2026

Abstract

Biomorphic hydroxyapatite scaffolds derived from rattan wood (GreenBone) show significant promise in bone tissue engineering due to their inherent structural similarity to natural bone. Laser-drilled GreenBone scaffolds were studied for enhanced porosity, nutrient diffusion, cellular infiltration, and vascularisation. Patient-derived bone marrow mesenchymal stromal/stem [...] Read more.

Biomorphic hydroxyapatite scaffolds derived from rattan wood (GreenBone) show significant promise in bone tissue engineering due to their inherent structural similarity to natural bone. Laser-drilled GreenBone scaffolds were studied for enhanced porosity, nutrient diffusion, cellular infiltration, and vascularisation. Patient-derived bone marrow mesenchymal stromal/stem cells (BMMSCs) and culture-expanded mesenchymal stem cells (cMSCs) demonstrated high cell viability (>90%), considerable adhesion, and extensive cytoskeletal organisation. Trilineage differentiation confirmed the multipotency of BMMSCs, with osteogenic, adipogenic, and chondrogenic markers being successfully expressed. BMMSCs and cMSCs exhibited enhanced differentiation and gene expression profiles. At week 4, key osteogenic and angiogenic genes such as BMP2, VEGFC, RUNX2, and COL1A1 showed elevated expression, indicating improved bone formation and vascularisation activity. Markers associated with extracellular matrix (ECM) remodelling, including MMP9 and TIMP1, were also upregulated, suggesting active tissue remodelling. ELISA analysis for VEGF further demonstrated increased VEGF secretion, highlighting the scaffold’s angiogenic potential. The improved cellular response and vascular signalling emphasise the translational relevance of laser-modified GreenBone scaffolds for bone tissue engineering, particularly for critical-sized defect repair requiring rapid vascularised bone regeneration. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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10 pages, 1530 KB

Open AccessArticle

Anodization and Its Role in Peri-Implant Tissue Adhesion: A Novel 3D Bioprinting Approach

by Béla Kolarovszki, Alexandra Steinerbrunner-Nagy, Dorottya Frank, Gábor Decsi, Attila Mühl, Beáta Polgár, Péter Maróti, Ákos Nagy, Judit E. Pongrácz and Kinga Turzó

J. Funct. Biomater. 2026, 17(2), 61; https://doi.org/10.3390/jfb17020061 - 26 Jan 2026

Abstract

Background: Soft tissue stability around dental implant abutments is critical for maintaining a functional peri-implant seal. Yellow anodization is used to improve the aesthetic and surface characteristics of titanium abutments, yet its epithelial effects under more physiologically relevant 3D conditions remain insufficiently explored. [...] Read more.

Background: Soft tissue stability around dental implant abutments is critical for maintaining a functional peri-implant seal. Yellow anodization is used to improve the aesthetic and surface characteristics of titanium abutments, yet its epithelial effects under more physiologically relevant 3D conditions remain insufficiently explored. Objective: To develop a 3D bioprinted in vitro peri-implant mucosa model and to compare epithelial cell responses on yellow anodized versus turned titanium abutment surfaces. Methods: Commercial Grade 5 (Ti6Al4V) titanium abutments were anodized and compared with turned controls. A collagen-based 3D bioprinted “collar-like” construct incorporating YD-38 epithelial cells was fabricated using a custom holder system to simulate peri-implant mucosal contact. Samples were cultured for 14 and 21 days. Cell distribution and morphology were assessed by optical microscopy and HE staining, while cytoskeletal organization was evaluated by TRITC-phalloidin/Hoechst staining and confocal microscopy. Quantitative fluorescence analysis was performed at 21 days. Results: Both surfaces supported epithelial coverage in the 3D environment. Anodized specimens showed more pronounced actin cytoskeletal organization and the presence of actin-rich, filamentous cellular extensions compared with turned controls. Quantitative image analysis demonstrated significantly higher TRITC-phalloidin signal intensity at 21 days on anodized samples (p < 0.001). Conclusions: Within the limitations of a 3D epithelial in vitro model using YD-38 cells, yellow anodization was associated with enhanced epithelial cytoskeletal organization compared with turned titanium. The presented 3D bioprinted platform may serve as a practical in vitro tool for screening abutment surface modifications relevant to peri-implant soft tissue integration. Full article

(This article belongs to the Special Issue 3D-Printed Biomaterials: Development, Optimization, and Biomedical Applications)

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22 pages, 3970 KB

Open AccessArticle

Electrospun Phage-Loaded Bilayer Nanofibrous Scaffolds for Wound Dressing Applications: A Comparative Study of Different Bacteriophages

by Siavash Aghili, Muhammed Awad, Md Hasib Adnan, George Bouras, Tran Thanh Tung, Sarah Vreugde and Dusan Losic

J. Funct. Biomater. 2026, 17(2), 60; https://doi.org/10.3390/jfb17020060 - 26 Jan 2026

Abstract

Antimicrobial resistance is a growing global health threat, necessitating alternatives to conventional antibiotics. Bacteriophages, viruses that specifically target bacteria, represent a promising option, and phage-loaded electrospun fibers have recently gained attention as wound dressings for localized phage therapy. However, the influence of phage [...] Read more.

Antimicrobial resistance is a growing global health threat, necessitating alternatives to conventional antibiotics. Bacteriophages, viruses that specifically target bacteria, represent a promising option, and phage-loaded electrospun fibers have recently gained attention as wound dressings for localized phage therapy. However, the influence of phage morphology and scaffold design has been largely overlooked. This study investigates how phage morphology and structure, in conjunction with scaffold design and processing conditions, may influence the biological performance of electrospun scaffolds. A bilayer scaffold was developed comprising a supportive polycaprolactone (PCL)/gelatin (70:30) layer and a polyvinyl alcohol (PVA) top layer loaded with bacteriophages. Two phage types, short-tailed podovirus APTC-SL.1 and long-tailed myovirus APTC-Efa.20, were incorporated into PVA fibers to evaluate their antibacterial activity against Staphylococcus lugdunensis and Enterococcus faecalis, respectively. The fibers were characterized using XRD, FTIR, TGA, optical microscopy, SEM, TEM, wettability analysis, and in vitro degradation tests. Biological assessments included antimicrobial testing, phage viability, and phage release. The bilayer scaffold containing short-tailed phages preserved phage viability and produced clear zones of lysis against S. lugdunensis, with ≈8.15% viability retained after electrospinning and relatively controlled release, whereas long-tailed phages showed no antibacterial activity. These results suggest that phage structure and morphology, together with electrospinning conditions and scaffold architecture, may play an important role in maintaining phage functionality in wound dressing applications, while acknowledging that host–phage interactions may also contribute to the observed differences. Full article

(This article belongs to the Section Antibacterial Biomaterials)

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17 pages, 9958 KB

Open AccessArticle

Medial Malleolar Fracture Fixation with Stainless Steel, Titanium, Magnesium, and PLGA Screws: A Finite Element Analysis

by Mehmet Melih Asoglu, Volkan Kızılkaya, Ali Levent, Huseyin Kursat Celik, Ozkan Kose and Allan E. W. Rennie

J. Funct. Biomater. 2026, 17(2), 59; https://doi.org/10.3390/jfb17020059 - 24 Jan 2026

Abstract

Background: Implant material may influence interfragmentary mechanics in medial malleolar (MM) fracture fixation. This study aimed to compare stainless steel, titanium, magnesium, and PLGA screws under identical conditions using finite element analysis (FEA). Methods: A CT-based ankle model with a unilateral oblique MM [...] Read more.

Background: Implant material may influence interfragmentary mechanics in medial malleolar (MM) fracture fixation. This study aimed to compare stainless steel, titanium, magnesium, and PLGA screws under identical conditions using finite element analysis (FEA). Methods: A CT-based ankle model with a unilateral oblique MM fracture (θ = 60° to the medial tibial plafond) was fixed with two parallel M4 × 35 mm screws placed perpendicular to the fracture plane (inter-axial distance 13 mm). Contacts were defined as nonlinear frictional, and each screw was assigned a pretension force of 2.5 N. Static single-leg stance was simulated with physiologic tibia/fibula load sharing. Four scenarios differed only by screw material. Primary outputs were interfragmentary micromotion (maximum sliding and gap). Secondary measures included fracture interface contact/frictional stresses, screw/bone von Mises stress, global construct displacement, and average tibiotalar cartilage contact pressure. Results: Interfragmentary micromotion increased as screw stiffness decreased. Maximum sliding was 32.2–33.8 µm with stainless steel/titanium, 40.4 µm with magnesium, and 65.0 µm with PLGA; corresponding gaps were 31.2–32.0 µm with stainless steel and titanium, 31.2 µm with magnesium, and 54.1 µm with PLGA, respectively. Interface stresses followed the same pattern: contact pressure (3.18–3.24 MPa for stainless steel/titanium/magnesium vs. 4.29 MPa for PLGA); frictional stress (1.46–1.49 MPa vs. 1.98 MPa). Peak screw von Mises stress was highest in stainless steel (104.1 MPa), then titanium (73.4 MPa), magnesium (47.4 MPa), and PLGA (17.9 MPa). Global axial displacement (0.26–0.27 mm) and average tibiotalar cartilage contact pressure (0.73–0.75 MPa) were essentially unchanged across materials. All conditions remained below commonly cited thresholds for primary bone healing (gap < 100 µm); however, PLGA exhibited a reduced safety margin. Conclusions: Under identical geometry and loading conditions, titanium and stainless steel yielded the most favorable interfragmentary mechanics for oblique MM fixation; magnesium showed intermediate performane, and PLGA produced substantially greater micromotion and interface stresses. These findings support the use of metallic screws when maximal initial stability is required and suggest that magnesium may be a selective alternative when reducing secondary implant removal is prioritized. Full article

(This article belongs to the Section Bone Biomaterials)

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24 pages, 4164 KB

Open AccessArticle

Antimicrobial Activity of Acidifying Hyaluronic Acid–Starch Microfiber Dressings Against Clinical Isolates from Chronic Wounds

by Ivana Stará, Petra Moťková, Markéta Vydržalová, Marcela Pejchalová, Ladislav Burgert, Radim Hrdina, Marek Bouška, Martin Adam, Karel Královec and Iveta Brožková

J. Funct. Biomater. 2026, 17(2), 58; https://doi.org/10.3390/jfb17020058 - 23 Jan 2026

Abstract

Hyaluronic acid (HA) is a natural biopolymer widely used in wound dressings for its supportive role in the healing process. In this study, we investigated the occurrence of microorganisms in chronic wounds and evaluated the antimicrobial activity of newly synthesized HA–Starch-based materials enriched [...] Read more.

Hyaluronic acid (HA) is a natural biopolymer widely used in wound dressings for its supportive role in the healing process. In this study, we investigated the occurrence of microorganisms in chronic wounds and evaluated the antimicrobial activity of newly synthesized HA–Starch-based materials enriched with acidifying agents. Microbial isolates obtained from chronic wounds were tested for susceptibility using the agar diffusion method. The prepared materials exhibited significant antimicrobial activity against both reference strains and multidrug-resistant clinical isolates. Further characterization by scanning electron microscopy and elemental analysis confirmed uniform microfiber morphology and the expected elemental composition of the fibers. Cytotoxicity assessments performed using the xCELLigence system demonstrated the potential safety of developed materials. Overall, the results indicate that HA–Starch-based materials containing acidifying compounds exhibit strong in vitro antimicrobial activity against chronic-wound isolates, supporting their potential for further evaluation in wound care applications. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

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Graphical abstract

15 pages, 11097 KB

Open AccessArticle

RNA-Seq of Gingival Fibroblasts Grown on Collagen Membranes and Hyaluronic Acid

by Layla Panahipour, Xiaoyu Huang and Reinhard Gruber

J. Funct. Biomater. 2026, 17(2), 57; https://doi.org/10.3390/jfb17020057 - 23 Jan 2026

Abstract

Purpose: Collagen membranes are widely used biomaterials in periodontal and implant dentistry and can be combined with hyaluronic acid (HA). Although collagen membranes are expected to exhibit bioactive properties and support fibroblast infiltration, their specific impact on fibroblast behavior remains unclear. Methods: To [...] Read more.

Purpose: Collagen membranes are widely used biomaterials in periodontal and implant dentistry and can be combined with hyaluronic acid (HA). Although collagen membranes are expected to exhibit bioactive properties and support fibroblast infiltration, their specific impact on fibroblast behavior remains unclear. Methods: To investigate this, human gingival fibroblasts were seeded on collagen matrices—mucoderm^®, a collagen fleece derived from dermis, and Jason^® membrane derived from pericardium—with or without lyophilized HA. Subsequent bulk RNA sequencing was used to assess transcriptional responses. Results: Both mucoderm^® and the collagen fleece caused significant transcriptional changes compared with fibroblasts grown on standard tissue culture surfaces and Jason^® membrane. These changes included upregulation of CEMIP, STC1, and TM4SF1, and downregulation of ADM2, PSAT1, and GPR1. Notably, the collagen fleece increased expression of extracellular matrix-related genes including CCN1, CCN2, COL1A1, POSTN, SPARC, TAGLN, FBN2, CCDC80, and CREB3L1 relative to mucoderm^®. Additionally, the expression of proteases MMP3 and MMP10, along with detoxification-related genes MT1E, MT2A, HMOX1, and NQO1, was relatively decreased. HA coating elevated IL24 expression in mucoderm^®, but no similar effect was observed in the collagen fleece. Conclusions: These findings demonstrate that collagen membranes can influence the transcriptome of gingival fibroblasts and suggest that collagen fleece has a stronger effect on extracellular matrix formation than mucoderm^®. Furthermore, HA coating does not consistently alter fibroblast responses. Full article

(This article belongs to the Special Issue Role of Dental Biomaterials in Promoting Oral Health)

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18 pages, 1992 KB

Open AccessArticle

Paeonia lactiflora Callus-Derived Polynucleotides Enhance Collagen Accumulation in Human Dermal Fibroblasts

by Soyoung Hwang, Seunghye Park, Jin Woo Lee, Mira Park, Le Anh Nguyet, Yongsung Hwang, Keunsun Ahn, Hyun-young Shin and Kuk Hui Son

J. Funct. Biomater. 2026, 17(1), 56; https://doi.org/10.3390/jfb17010056 - 22 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Natural Biomaterials for Biomedical Applications)

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22 pages, 1861 KB

Open AccessArticle

Differential Expression of S100A Genes in hDPSCs Following Stimulation with Two Hydraulic Calcium Silicate Cements: A Laboratory Investigation

by Holger Jungbluth, Diana Lalaouni, Jochen Winter, Søren Jepsen and Dominik Kraus

J. Funct. Biomater. 2026, 17(1), 55; https://doi.org/10.3390/jfb17010055 - 21 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Dental Biomaterials)

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20 pages, 4212 KB

Open AccessArticle

Analysis of the Feasibility of Concurrent Application of Magnetic Nanoparticles as MRI Contrast Agents and for Magnetic Hyperthermia

by 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 and Piotr Bogorodzki

J. Funct. Biomater. 2026, 17(1), 54; https://doi.org/10.3390/jfb17010054 - 21 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials for Cancer Therapies)

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38 pages, 4278 KB

Open AccessReview

Fibrous Biomaterial Scaffold for Tympanic Membrane Repair: Microarchitectural Engineering and Structure Function Performance

by Lea Jiang, Chokri Cherif and Michael Wöltje

J. Funct. Biomater. 2026, 17(1), 53; https://doi.org/10.3390/jfb17010053 - 21 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)

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17 pages, 7685 KB

Open AccessArticle

Biomechanical Stimulation of Mesenchymal Stem Cells in 3D Peptide Nanofibers for Bone Differentiation

by Faye Fouladgar, Robert Powell, Emily Carney, Andrea Escobar Martinez, Amir Jafari and Neda Habibi

J. Funct. Biomater. 2026, 17(1), 52; https://doi.org/10.3390/jfb17010052 - 19 Jan 2026

Abstract

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 [...] Read more.

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

\approx 0.85

), and significantly increased proliferation compared to static or high-frequency (2.5 Hz, 1%) conditions (coherency index

\approx 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. Full article

(This article belongs to the Section Biomaterials for Tissue Engineering and Regenerative Medicine)

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3 pages, 154 KB

Open AccessEditorial

From Scaffolds to Complex Systems: Functional Biomaterials in Regenerative Medicine

by Cristian Scheau, Andreea Cristiana Didilescu and Constantin Caruntu

J. Funct. Biomater. 2026, 17(1), 51; https://doi.org/10.3390/jfb17010051 - 19 Jan 2026

Abstract

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 [...] Full article

(This article belongs to the Special Issue The 15th Anniversary of JFB—Functional Biomaterials: Bioactive Properties and Medical Applications)

17 pages, 3200 KB

Open AccessArticle

The Self-Assembling Peptide P₁₁-4 Induces the Expression of Mineralization-Related Genes in Odontoblasts Independently of Metabolic Alterations

by Leticia Martins Pereira, Marina Damasceno e Souza de Carvalho Chiari, Diego Mauro Carneiro Pereira, Regina Maria Puppin-Rontani and Fábio Dupart Nascimento

J. Funct. Biomater. 2026, 17(1), 50; https://doi.org/10.3390/jfb17010050 - 18 Jan 2026

Abstract

(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 [...] Read more.

(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. Full article

(This article belongs to the Special Issue Biomaterials in Restorative Dentistry and Endodontics (2nd Edition))

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15 pages, 1527 KB

Open AccessArticle

Dental Implants Used for Orthodontic Anchorage in Patients with Treated Stage IV Periodontitis: A Retrospective Case–Control Study

by Shing-Zeng Dung and I-Shiang Tzeng

J. Funct. Biomater. 2026, 17(1), 49; https://doi.org/10.3390/jfb17010049 - 18 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Functional Dental Materials for Orthodontics and Implants)

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18 pages, 971 KB

Open AccessSystematic Review

Efficacy of Etidronic Acid for Smear Layer Removal: A Systematic Review of In Vitro Studies

by María-Inmaculada Vidal-Montolío, José Luis Sanz, James Ghilotti, Sofía Folguera and Carmen Llena

J. Funct. Biomater. 2026, 17(1), 48; https://doi.org/10.3390/jfb17010048 - 16 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Advanced Biomaterials and Biotechnology: Applications in Dental Medicine—2nd Edition)

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20 pages, 1826 KB

Open AccessArticle

Tension-Dominant Orthodontic Loading and Buccal Periodontal Phenotype Preservation: An Integrative Mechanobiological Model Supported by FEM and a Proof-of-Concept CBCT

by Anna Ewa Kuc, Jacek Kotuła, Kamil Sybilski, Szymon Saternus, Jerzy Małachowski, Natalia Kuc, Grzegorz Hajduk, Joanna Lis, Beata Kawala, Michał Sarul and Magdalena Sulewska

J. Funct. Biomater. 2026, 17(1), 47; https://doi.org/10.3390/jfb17010047 - 16 Jan 2026

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Functional Dental Materials for Orthodontics and Implants)

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13 pages, 3249 KB

Open AccessArticle

Clinical Success Rates of Dental Implants with Bone Grafting in a Large-Scale National Dataset

by Mordechai Findler, Haim Doron, Jonathan Mann, Tali Chackartchi and Guy Tobias

J. Funct. Biomater. 2026, 17(1), 46; https://doi.org/10.3390/jfb17010046 - 15 Jan 2026

Abstract

Objective: To evaluate the clinical success outcomes and risk factors associated with dental implants placed with simultaneous bone augmentation in a large-scale, real-world cohort. Methods: A retrospective analysis was conducted on 158,824 implants, including 45,715 Dental Bone Grafts, placed between 2014 and 2022 [...] Read more.

Objective: To evaluate the clinical success outcomes and risk factors associated with dental implants placed with simultaneous bone augmentation in a large-scale, real-world cohort. Methods: A retrospective analysis was conducted on 158,824 implants, including 45,715 Dental Bone Grafts, placed between 2014 and 2022 within a national healthcare network. Multivariate Generalized Estimating Equations were utilized to assess the impact of demographic, anatomical, and procedural variables on implant failure. Results: The augmented cohort demonstrated a high clinical success rate of 97.83% (2.17% failure), statistically comparable to the general implant population. Failures were predominantly early (<1 year), accounting for 70% of losses. Significant independent risk factors included immediate implant placement (3.08% failure vs. 2.07% for delayed), male gender, and maxillary location. Notably, low socioeconomic status (SES) emerged as a significant predictor, with a failure rate of 3.07% compared to 2.06% in high-SES groups. Conclusions: Simultaneous bone augmentation is a predictable modality that does not inherently increase implant failure risk, supporting the stabilization hypothesis. However, failure is modulated by specific variables. The identification of lower SES, male gender, and immediate placement as significant risk indicators highlights the necessity for personalized risk assessment and targeted protocols to optimize outcomes in augmented sites. Full article

(This article belongs to the Special Issue Biomaterials for Periodontal and Peri-Implant Regeneration)

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28 pages, 30300 KB

Open AccessReview

An Exploration of Nanobiotechnology Bridging Patho-Therapeutics with Regenerative and Clinical Perspectives in Periodontitis

by Baozhu Zhang, Muhammad Umar Javed, Yinghe Zhang and Bing Guo

J. Funct. Biomater. 2026, 17(1), 45; https://doi.org/10.3390/jfb17010045 - 15 Jan 2026

Abstract

Periodontal disease represents a major global concern characterized by chronic biofilm-driven inflammation, excessive oxidative stress, progressive tissue destruction, and impaired regenerative capacity. Beyond conventional antimicrobial approaches, recent progress has shifted toward host-directed and regenerative therapeutic strategies aimed at restoring both oral function and [...] Read more.

Periodontal disease represents a major global concern characterized by chronic biofilm-driven inflammation, excessive oxidative stress, progressive tissue destruction, and impaired regenerative capacity. Beyond conventional antimicrobial approaches, recent progress has shifted toward host-directed and regenerative therapeutic strategies aimed at restoring both oral function and tissue homeostasis. This review consolidates current developments in nanobiotechnology-based materials that modulate immune responses, scavenge reactive oxygen species, and promote angiogenesis and osteogenesis, thereby facilitating the effective regeneration of dental and periodontal tissues. Emphasis is placed on bioresponsive hydrogels, bioactive scaffolds, and gas-releasing platforms that integrate therapeutic regulation with tissue repair. The discussion further highlights key advances in polymeric and inorganic biomaterials designed to balance antibacterial action with cellular compatibility and regenerative potential. By linking pathophysiological mechanisms with material-guided healing processes, this review provides a comprehensive perspective on emerging nanobiotechnological solutions that bridge patho-therapeutics with regenerative and clinical dentistry. Full article

(This article belongs to the Section Dental Biomaterials)

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