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J. Funct. Biomater., Volume 17, Issue 3 (March 2026) – 52 articles

Cover Story (view full-size image): This study investigates the in vivo biodegradation and biodistribution of a BMP-2-binding peptide amphiphile supramolecular implant designed as an osteoinductive biomaterial for spinal fusion. In a rat posterolateral fusion model, longitudinal MRI and ICP-MS analyses of a gadolinium-labelled implant demonstrated progressive clearance from the fusion site, minimal off-target accumulation, and only low-level transient uptake in the liver. Micro-CT and histology confirmed robust fusion, indicating preserved implant bioactivity. These findings provide key preclinical data to support the translational potential of this BMP-2-binding implant technology for effective spinal fusion. View this paper
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24 pages, 4170 KB  
Article
Surface-Activated Zirconia Nanotubes with UV-Assisted Mg Deposition: Novel Bioinstructive Implants
by Swathi N. V. Raghu, Yomna Badran, Shanmugapriya Periyannan and Manuela S. Killian
J. Funct. Biomater. 2026, 17(3), 158; https://doi.org/10.3390/jfb17030158 - 23 Mar 2026
Viewed by 1081
Abstract
Modern bioimplants increasingly depend on surface-engineered functionality to elicit adaptive biological responses. One promising strategy involves the electrodeposition of bioresponsive elements such as magnesium (Mg), which plays a critical role in osseointegration. In this study, we present a novel approach for modifying anodized [...] Read more.
Modern bioimplants increasingly depend on surface-engineered functionality to elicit adaptive biological responses. One promising strategy involves the electrodeposition of bioresponsive elements such as magnesium (Mg), which plays a critical role in osseointegration. In this study, we present a novel approach for modifying anodized zirconia nanotubes (ZrNTs) via Mg decoration using electrochemical deposition. A controlled pulsed cathodic linear sweep protocol was employed to control Mg deposition behaviour, enabling reduced clustering and improved spatial distribution. Notably, ultraviolet (UV) irradiation was found to influence Mg adsorption dynamics, revealing a distinct pattern of interaction. Comprehensive surface characterization was conducted to assess nanotube morphology, Mg adherence, and distribution. These modified surfaces were subsequently evaluated for their potential in further functionalization, targeting surface chemistries conducive to biomaterial viability. The biomineralization capacity of Mg-decorated ZrNTs was systematically investigated using electrochemical impedance spectroscopy (EIS) and Tafel analysis, demonstrating enhanced apatite formation and improved corrosion resistance. This work establishes Mg decoration of ZrNTs as a viable route for developing bioactive, corrosion-resistant implant surfaces. Full article
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14 pages, 2508 KB  
Article
The Effect of Surface Pretreatments on the Bond Strength of Hybrid CAD/CAM with Composite Elevation
by Mehmet Ali Fildisi, Burcu Oglakci Ozkoc, Zumrut Ceren Ozduman and Evrim Eliguzeloglu Dalkilic
J. Funct. Biomater. 2026, 17(3), 157; https://doi.org/10.3390/jfb17030157 - 23 Mar 2026
Viewed by 874
Abstract
In computer-aided design/computer-aided manufacturing (CAD/CAM) restorations for severely damaged teeth, the cavity floor or proximal margins may be elevated with composite resin to improve adhesion. This in vitro study investigated how different surface pretreatment methods affect the shear bond strength (SBS) of hybrid [...] Read more.
In computer-aided design/computer-aided manufacturing (CAD/CAM) restorations for severely damaged teeth, the cavity floor or proximal margins may be elevated with composite resin to improve adhesion. This in vitro study investigated how different surface pretreatment methods affect the shear bond strength (SBS) of hybrid CAD/CAM materials to dentin or composite surfaces, simulating clinical situations of composite elevation. Hybrid CAD/CAM samples were bonded to dentin or composite substrates following different surface pretreatment protocols and cemented using a dual-cure adhesive resin cement. The samples were thermocycled and subjected to shear bond strength testing, and failure modes were analyzed. The SBS in the sandblasting (SB)+Dentin group and hydrofluoric acid (HF)+Dentin was significantly higher than that in the SB+Composite and HF+Composite groups (p < 0.05). Untreated+composite and untreated+dentin groups showed significantly lower SBS (p < 0.05). Failure mode analysis revealed a predominance of cohesive failures in the SB+Dentin group, while adhesive failures were more frequently observed in most of the other groups. SB-treated and HF-etched hybrid CAD/CAM materials showed more favorable bonding behavior to dentin than to composite, highlighting that bonding to the elevated composite layer may be less effective than bonding directly to prepared dentin. Full article
(This article belongs to the Section Dental Biomaterials)
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25 pages, 799 KB  
Review
Heparin-Based Biomaterials for Sustained Release of Growth Factors for Bone Tissue Engineering and Regeneration
by Keisuke Nakayama, Xueqin Gao, Britney S. Force, Marc J. Philippon and Johnny Huard
J. Funct. Biomater. 2026, 17(3), 156; https://doi.org/10.3390/jfb17030156 - 22 Mar 2026
Cited by 1 | Viewed by 1557
Abstract
Large bone defects resulting from trauma, tumor resection, infection, or degenerative diseases pose a major clinical challenge in orthopedic surgery and regenerative medicine. Despite advances in biomaterials and surgical techniques, successful outcomes are often compromised by poor vascularization, limited osteoinduction, and donor-site morbidity [...] Read more.
Large bone defects resulting from trauma, tumor resection, infection, or degenerative diseases pose a major clinical challenge in orthopedic surgery and regenerative medicine. Despite advances in biomaterials and surgical techniques, successful outcomes are often compromised by poor vascularization, limited osteoinduction, and donor-site morbidity associated with autografts or allografts. However, conventional delivery systems suffer from burst release, rapid clearance, off-target effects, and supraphysiologic dosing, which can lead to undesirable complications such as ectopic ossification and inflammation, with some reports raising concerns about the long-term tumorigenic risk. Heparin, a naturally highly sulfated glycosaminoglycan structurally related to heparan sulfate, has emerged as a particularly attractive candidate for affinity-based biomaterial systems. It naturally binds over 300 growth factors, including bone morphogenetic proteins. By protecting these proteins from enzymatic degradation, enhancing their bioavailability, and mediating receptor clustering, heparin provides both biochemical stability and biofunctional modulation. This review provides a comprehensive overview of heparin-based delivery strategies in bone tissue engineering. We begin by describing the biological functions of heparin in modulating growth factor activity. We then discuss in detail the different heparin-based biomaterials designed to sustain the release of growth factors for bone tissue engineering, including the heparin–polycation coacervate system; heparin-based supramolecules; and heparin-based hydrogels, nanoparticles, and microspheres for sustained release of bone morphogenic proteins and other growth factors for bone tissue engineering. Finally, we assess the clinical and translational relevance of heparin-based systems, identify key challenges, and outline future perspectives, highlighting the potential of these biomaterials for providing safer and more effective therapies for bone regeneration. Full article
(This article belongs to the Special Issue Advanced Biomaterials for Bone Tissue Engineering)
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26 pages, 4906 KB  
Article
A Borophosphate Glass Doped with Cobalt Oxide Improves Skeletal Muscle Structure and Function in Myopathic Mice
by Jacob A. Kendra, Alexandra G. Naman, Rebekah L. Blatt, Carla D. Zingariello, Richard K. Brow, Steven S. Segal and Aaron B. Morton
J. Funct. Biomater. 2026, 17(3), 155; https://doi.org/10.3390/jfb17030155 - 20 Mar 2026
Viewed by 1458
Abstract
Skeletal muscle myopathy remains a significant cause of disability with limited treatment strategies. Advancements in tissue engineering have led to the development of borophosphate bioactive glasses (BPBGs) capable of enhancing skeletal muscle structure and function. Using a mouse model of severe myopathy (D2. [...] Read more.
Skeletal muscle myopathy remains a significant cause of disability with limited treatment strategies. Advancements in tissue engineering have led to the development of borophosphate bioactive glasses (BPBGs) capable of enhancing skeletal muscle structure and function. Using a mouse model of severe myopathy (D2.mdx), we investigated muscle force, regeneration, angiogenesis and inflammation at 14, 70 and 140 days post-treatment (dpt). Tibialis anterior (TA) muscles of D2.mdx mice that received a single injection of cobalt oxide-doped BPBG (CoO-TRIM) particles exhibit greater active force, myofiber size, and regeneration through 70 dpt compared to control D2.mdx mice injected with Saline. Vascular endothelial growth factor (VEGF) was elevated up to 70 dpt in D2.mdx CoO-TRIM mice followed by increased muscle vascularity. As a marker of inflammation, interleukin (IL)-6 increased in D2.mdx CoO-TRIM mice compared to D2.mdx Saline controls at 14 dpt, with no differences at 70 or 140 dpt. No differences were observed in outcome measures between wild-type (WT) CoO-TRIM mice and WT Saline controls. We report that CoO-TRIM can stimulate VEGF production and promote restoration of muscle structure and function when inflammation is present. Local injection of an inorganic biomaterial alone can benefit myopathic skeletal muscle. Full article
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12 pages, 266 KB  
Review
Hyaluronic Acid as an Adjunctive Therapy in Periodontal and Dental Treatment of Medically Compromised Patients: A Narrative Review
by Meizi Eliezer, Ruxandra Christodorescu, Alla Belova, Darian Rusu, Stefan Milicescu, Moshe Cohen and Stefan-Ioan Stratul
J. Funct. Biomater. 2026, 17(3), 154; https://doi.org/10.3390/jfb17030154 - 20 Mar 2026
Cited by 2 | Viewed by 1763
Abstract
Hyaluronic acid (HA) is a biologically active glycosaminoglycan with recognized roles in wound healing and inflammation modulation, and its adjunctive use in dental and periodontal therapy has gained interest, particularly in medically compromised patients. This narrative review critically evaluated preclinical and clinical evidence [...] Read more.
Hyaluronic acid (HA) is a biologically active glycosaminoglycan with recognized roles in wound healing and inflammation modulation, and its adjunctive use in dental and periodontal therapy has gained interest, particularly in medically compromised patients. This narrative review critically evaluated preclinical and clinical evidence on locally applied HA in periodontal, oral surgical, peri-implant, and oral medicine treatments in patients with systemic conditions. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (January 2015–December 2025) identified in vivo translational studies, randomized and controlled clinical trials, and selected systematic reviews involving medically compromised populations. Qualitative synthesis focused on biological plausibility, clinical outcomes, and safety. Nine core studies were included, comprising two preclinical in vivo investigations and seven clinical trials. In diabetic models, cross-linked high-molecular-weight HA reduced macrophage infiltration and delayed collagen membrane degradation without impairing angiogenesis. Clinically, adjunctive HA use in patients with type 2 diabetes mellitus was associated with modest but statistically significant short-term improvements in clinical attachment level (CAL) and enhanced early soft tissue healing following tooth extraction. In peri-implantitis therapy and oncology-related oral complications, HA application was linked to reduced inflammatory markers, decreased lesion severity, and improved patient-reported symptoms. No systemic adverse effects were reported. Overall, HA appears to be a locally safe adjunct that may support early healing and inflammation control in medically compromised patients, although its effects are primarily short-term and do not indicate disease-modifying potential. Full article
(This article belongs to the Special Issue Biomaterials for Periodontal and Peri-Implant Regeneration)
11 pages, 1596 KB  
Communication
Amino-Modified Mesoporous Bioactive Glass Adsorbed with Osteopontin Enhances Osteogenic Differentiation and Matrix Mineralization via the Erk1/2 Signaling Pathway
by Ying Yang, Kunlu Lin, Zheng Zhou, Libangxi Liu, Long Liu, Haoming Liu, Hanyue Mao and Xiaoyan Wang
J. Funct. Biomater. 2026, 17(3), 153; https://doi.org/10.3390/jfb17030153 - 19 Mar 2026
Viewed by 797
Abstract
Mesoporous bioactive glass (MBG) has been extensively studied in bone regeneration due to its excellent bioactivity and osteoconductive properties. Here, we prepared amino-modified MBG (MBG-NH2) adsorbed osteopontin (OPN) to form MBG-NH2/OPN composites, enabling the sustained release of OPN and [...] Read more.
Mesoporous bioactive glass (MBG) has been extensively studied in bone regeneration due to its excellent bioactivity and osteoconductive properties. Here, we prepared amino-modified MBG (MBG-NH2) adsorbed osteopontin (OPN) to form MBG-NH2/OPN composites, enabling the sustained release of OPN and enhancing osteoblast differentiation and mineralization capacity. Interestingly, we observed that MBG-NH2 promotes the formation of osteoid deposits and calcium deposition in vitro. Furthermore, we also found that MBG-NH2/OPN significantly enhances cell adhesion, differentiation, and mineralization. Consistent with these observations, we found the expression of the osteoblast-specific marker gene increased, including bone morphogenetic protein 2 (Bmp2) and Collagen I. Intriguingly, we also found that MBG-NH2/OPN promotes osteoblast differentiation and mineralization through activating the extracellular regulated protein kinases1/2 (Erk1/2) signaling pathway. We concluded that MBG-NH2/OPN enhances osteoblast differentiation and mineralization through the Erk1/2 pathway. These findings indicate that MBG-NH2/OPN is a new potential biomaterial for bone regeneration. Full article
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35 pages, 2964 KB  
Review
Green Palladium Nanoparticles: Mechanism of Synthesis and Biomedical Application
by Ekaterina O. Mikhailova
J. Funct. Biomater. 2026, 17(3), 152; https://doi.org/10.3390/jfb17030152 - 19 Mar 2026
Cited by 1 | Viewed by 1666
Abstract
Green synthesis of nanoparticles has become one of the most popular research areas in recent decades due to its environmentally friendly nature and the minimization of harmful chemical by-products. This review focuses on the mechanism of palladium nanoparticle (PdNP) biosynthesis using bacteria, fungi, [...] Read more.
Green synthesis of nanoparticles has become one of the most popular research areas in recent decades due to its environmentally friendly nature and the minimization of harmful chemical by-products. This review focuses on the mechanism of palladium nanoparticle (PdNP) biosynthesis using bacteria, fungi, algae, and plants, and their potential biological activities, such as antibacterial, anticancer, antioxidant, and other properties, with the aim of their further biomedical applications. The role of various biomolecules in these processes is also discussed. Full article
(This article belongs to the Special Issue Emerging Trends of Nanomaterials in Biology)
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15 pages, 2181 KB  
Article
A Flexible and Thermally Uniform TiO2/Ag/SiO2 Transparent Heater for Skin-Integrated Applications
by Jaejeong Jo, Geonwoo Kang, Chankyoung Lee, Tran Thi Bao Vo and Dooho Choi
J. Funct. Biomater. 2026, 17(3), 151; https://doi.org/10.3390/jfb17030151 - 18 Mar 2026
Viewed by 1262
Abstract
Transparent heaters intended for skin-contacting applications must simultaneously satisfy optical transparency, mechanical compliance, thermal uniformity, and operational safety under biologically relevant temperature ranges. Here, we evaluate the applicability of a TiO2/Ag/SiO2 (TAS) dielectric–metal–dielectric transparent heater as a functional biomaterial platform [...] Read more.
Transparent heaters intended for skin-contacting applications must simultaneously satisfy optical transparency, mechanical compliance, thermal uniformity, and operational safety under biologically relevant temperature ranges. Here, we evaluate the applicability of a TiO2/Ag/SiO2 (TAS) dielectric–metal–dielectric transparent heater as a functional biomaterial platform for wearable and skin-integrated thermal systems. By systematically optimizing each layer thickness of the TAS structure, the heater achieves high visible-light transmittance (average of 86.6%) together with low sheet resistance on the order of 7.7 Ω/sq for low-voltage operation. The TAS heater demonstrates rapid and reproducible Joule-heating behavior, showing fast thermal response with short thermal time constants and spatially homogeneous temperature distributions without localized hot spots. Stable electrothermal performance is maintained under repeated on/off cycling and during cyclic mechanical bending down to small radii, confirming excellent mechanical stability under repeated bending relevant to wearable applications. Importantly, direct on-skin evaluations conducted by attaching the device to a human elbow reveal conformal contact, uniform heating at therapeutically relevant temperatures (50–70 °C), and stable operation under dynamic bending and extension. The absence of thermal inhomogeneity during motion highlights the intrinsic stability of the TAS architecture for skin-interfaced use. Given the high optical visibility, mechanical compliance, thermal uniformity, and electrothermal stability, the proposed TAS architecture represents a promising functional biomaterial platform for wearable thermotherapy, skin-mounted healthcare devices, and human-interactive thermal systems operating under continuous mechanical deformation and direct skin contact. Full article
(This article belongs to the Special Issue Advanced Materials and Devices for Medical Interventions)
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20 pages, 2684 KB  
Article
Acute Oroantral Communication Closure: Resorbable Collagen Membrane vs. Buccal Advancement Flap Outcomes: A Clinical Trial
by Agnieszka Balicz, Agnieszka Szurko, Magdalena Jędzierowska, Agnieszka Kiełboń, Sylwia Wójcik, Jakub Adamczyk, Martin Starosta, Jakub Fiegler-Rudol and Tadeusz Morawiec
J. Funct. Biomater. 2026, 17(3), 150; https://doi.org/10.3390/jfb17030150 - 18 Mar 2026
Viewed by 1367
Abstract
Background: Oroantral communication (OAC) is a frequent complication after the extraction of maxillary posterior teeth and requires immediate closure to prevent sinus pathology and long-term functional impairment. Objectives: This study aimed to compare the clinical and radiographic outcomes of acute OAC [...] Read more.
Background: Oroantral communication (OAC) is a frequent complication after the extraction of maxillary posterior teeth and requires immediate closure to prevent sinus pathology and long-term functional impairment. Objectives: This study aimed to compare the clinical and radiographic outcomes of acute OAC closure using resorbable heterogeneous collagen membranes with those of the conventional buccal advancement flap (Rehrmann method). Methods: Twenty-four patients with OACs diagnosed within 24 h post-extraction were enrolled, and 20 completed follow-up. Patients were allocated to a membrane group treated with a resorbable collagen membrane (Creos Xenoprotect) or a control group treated with a buccal advancement flap. Clinical parameters, including vestibular depth, width of keratinized gingiva, alveolar socket dimensions, postoperative complications, and pain intensity assessed using the Visual Analogue Scale, were evaluated at 1, 7, 14, and 90 days. Radiographic outcomes were assessed using cone-beam computed tomography with linear measurements and normalized bone density analysis in Hounsfield Units at baseline and 90 days. Results: The membrane technique provided significantly better preservation of vestibular depth, keratinized gingiva width, and alveolar socket dimensions, with significantly lower postoperative pain and fewer complications compared with the buccal advancement flap. Higher normalized bone density values were observed in the membrane group, although differences were not statistically significant. Conclusions: Resorbable collagen membranes represent a safe, minimally invasive, and clinically effective alternative to buccal advancement flaps for acute OAC closure. Full article
(This article belongs to the Section Dental Biomaterials)
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17 pages, 3311 KB  
Article
Mechanostat-Informed Strain Mapping of Osseodensification-Inspired Peri-Implant Densification Versus Conventional Drilling in Osteoporotic-like Low-Density Cancellous Bone: A 3D Static Linear Finite Element Analysis
by Mesut Tuzlali, Nagehan Baki, Nazik İrem Önügören, Kübra Aral, Erkan Bahçe and Cüneyt Asım Aral
J. Funct. Biomater. 2026, 17(3), 149; https://doi.org/10.3390/jfb17030149 - 18 Mar 2026
Cited by 1 | Viewed by 1119
Abstract
Low-density cancellous bone results in reduced trabecular support and may increase crestal cortical strain around implants. Osseodensification (OD) compacts trabecular bone and may create a peri-osteotomy densified zone, but its strain-level effects in osteoporotic-like bone are unclear. This study evaluated whether an OD-inspired [...] Read more.
Low-density cancellous bone results in reduced trabecular support and may increase crestal cortical strain around implants. Osseodensification (OD) compacts trabecular bone and may create a peri-osteotomy densified zone, but its strain-level effects in osteoporotic-like bone are unclear. This study evaluated whether an OD-inspired peri-implant densified trabecular zone reduces crestal cortical strain compared with conventional drilling (CD) in an osteoporotic-like model. A three-dimensional finite element model of a mandibular posterior segment with a 2.0-mm cortical shell and D4 cancellous core was constructed with a 4.3 × 11.4-mm titanium implant and a cemented monolithic zirconia crown. CD used a 4.0-mm osteotomy in D4 bone. The OD model used the same osteotomy plus a concentric peri-implant densified shell with radial density gradation from D1 to D3. The implant–bone interface was defined as bonded. Static 100 N axial and 45° oblique loads were applied. Outcomes were εeq, εmax, and εmin, summarized as mean top-10 nodal values. OD reduced crestal cortical strains under both loads. Under axial loading, εeq, εmax, and |εmin| decreased by 17.7%, 19.0%, and 24.1%, respectively. Under oblique loading, the corresponding reductions were 9.8%, 8.0%, and 8.9%. Oblique loading produced higher cortical strains than axial loading in both models. OD-inspired peri-implant densification reduced crestal cortical strain in this osteoporotic-like model, whereas oblique loading remained the main driver of elevated strain. These findings support occlusal/prosthetic strategies that minimize oblique forces and warrant experimental and clinical validation. Full article
(This article belongs to the Section Dental Biomaterials)
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15 pages, 16080 KB  
Article
In Vitro and In Ovo CAM Model Evaluation of Periosteum-Derived Micrografts
by Rawan Almujaydil, Conor J. McCann, Linh Nguyen and Francesco D’Aiuto
J. Funct. Biomater. 2026, 17(3), 148; https://doi.org/10.3390/jfb17030148 - 18 Mar 2026
Viewed by 2257
Abstract
Despite advances in periodontal regenerative therapies, consistent tissue regeneration remains challenging, with cells playing an essential role in successful repair. Therefore, this study tested different dental bone substitutes embedded in the chorioallantoic membrane (CAM) combined with periosteum-derived micrografts obtained using a chair-side device [...] Read more.
Despite advances in periodontal regenerative therapies, consistent tissue regeneration remains challenging, with cells playing an essential role in successful repair. Therefore, this study tested different dental bone substitutes embedded in the chorioallantoic membrane (CAM) combined with periosteum-derived micrografts obtained using a chair-side device (Rigenera HBW system). Cell populations within the micrografts were identified and characterised via immunofluorescence and flow cytometry (CD31, CD105, CD34, CD90, CD73, and CD45). A CAM model was employed to examine the angiogenic potential of micrografts combined with bone substitutes, which were analysed through quantitative blood vessel/vascularisation assessments using the Ikosa software (2025), along with histological and immunohistochemical evaluations such as smooth muscle actin (SMA), H&E, and Masson’s trichrome staining. Statistical analysis was performed using GraphPad Prism 10. The addition of periosteum-derived micrografts resulted in angiogenic enhancement compared to the controls. Notable enhancement of total vessel area, total length, and branching points were obtained when Fisiograft® (p = 0.0007, p = 0.0002, and p < 0.0001, respectively), New Shore® (p = 0.0006, p = 0.0149, and p = 0.0083, respectively), and Bio-Oss® (p = 0.0038 and p = 0.0010, respectively) were combined with micrografts, compared to the positive controls. The histological and immunohistochemical analyses confirmed increased vascularisation (positive staining for SMA) in the micrograft groups. Periosteum-derived micrografts represent a promising adjunct to conventional bone-grafting materials, promoting vascularisation and potentially enhancing tissue regeneration and healing outcomes. Full article
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25 pages, 2162 KB  
Systematic Review
Resin-Modified Calcium Silicate-Based Materials Versus Conventional Formulations in Primary Teeth: A Systematic Review and Meta-Analysis of Clinical and Radiographic Outcomes of Vital Pulp Therapy Procedures in Pediatric Dentistry
by Alberto Cabrera-Fernández, Laura Dominguez-Dominguez, Antonio Pérez-Pérez, João Miguel Marques dos Santos, Aránzazu Díaz-Cuenca, Victor Sanchez-Margalet, Diana B. Sequeira, Juan Jose Segura-Egea and Jenifer Martín-González
J. Funct. Biomater. 2026, 17(3), 147; https://doi.org/10.3390/jfb17030147 - 17 Mar 2026
Viewed by 1118
Abstract
Vital pulp therapy comprises a group of procedures whose use in the primary dentition is increasingly supported in pediatric dentistry. The clinical management of pediatric patients requires biomaterials that provide precision, ease of handling, and reduced chairside time; in this context, resin-modified calcium [...] Read more.
Vital pulp therapy comprises a group of procedures whose use in the primary dentition is increasingly supported in pediatric dentistry. The clinical management of pediatric patients requires biomaterials that provide precision, ease of handling, and reduced chairside time; in this context, resin-modified calcium silicate-based materials (RM-CSCs) have been introduced as an alternative to conventional calcium silicate formulations. This systematic review and meta-analysis aimed to evaluate the clinical effectiveness of RM-CSCs compared with non-resin calcium silicate-based materials in vital pulp therapy performed in primary teeth. A systematic search was conducted in MEDLINE, Scopus, Embase, and Web of Science in accordance with PRISMA guidelines. Randomized clinical trials were included, the risk of bias was assessed using the RoB 2 tool, and the certainty of evidence was evaluated using the GRADE approach. Of the 605 records initially identified, nine randomized clinical trials were ultimately included, all of which evaluated TheraCal LC as the RM-CSC. Meta-analyses were performed for vital pulp therapy overall and for procedure-specific subanalyses, including indirect pulp capping and pulpotomy. None of the meta-analyses demonstrated statistically significant differences between RM-CSCs and non-resin calcium silicate-based materials in terms of clinical or radiographic success. Therefore, the available evidence supports the use of TheraCal LC as an effective option for indirect pulp capping in primary teeth; however, its use in pulpotomy should be interpreted with caution until further randomized clinical trials become available. Full article
(This article belongs to the Special Issue Role of Dental Biomaterials in Promoting Oral Health)
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27 pages, 7352 KB  
Article
Cytocompatibility Assessment of L-PBF-Manufactured Zinc–Silver–Copper Alloys for Customized Biodegradable Medical Implants
by Barbara Illing, Jacob Schultheiss, Lukas Schumacher, Evi Kimmerle-Mueller, Ariadne Roehler, Alexander Heiss, Ulrich E. Klotz, Victor O. Okafor, Stefanie Krajewski and Frank Rupp
J. Funct. Biomater. 2026, 17(3), 146; https://doi.org/10.3390/jfb17030146 - 17 Mar 2026
Viewed by 1681
Abstract
Biodegradable zinc (Zn) has attracted increasing interest as a material for temporary implants, primarily due to its moderate degradation kinetics. In recent years, additive manufacturing of Zn alloys using the laser powder bed fusion method (L-PBF) has shown promising results. Compared to as-cast [...] Read more.
Biodegradable zinc (Zn) has attracted increasing interest as a material for temporary implants, primarily due to its moderate degradation kinetics. In recent years, additive manufacturing of Zn alloys using the laser powder bed fusion method (L-PBF) has shown promising results. Compared to as-cast Zn alloys, it offers preferable customized solutions for patient-specific temporary biomedical implants. Due to the novelty of these printed degradable biomaterials and due to reported cytotoxic effects of Zn alloys, this study investigates additively manufactured ZnAgCu, ZnAgCuMn, and ZnAgCuTi alloys, both in as-printed and post-processed conditions, with a focus on L929 and SAOS-2 biocompatibility. In this work, we demonstrate that the increased porosity and therefore larger surface areas compared to polished Zn-alloy samples affect their biocompatibility. Minimal to no cell proliferation was observed on and near the Zn-alloy test plates after 24 h. Undiluted extracts from as-cast Zn and L-PBF-manufactured plates were initially cytotoxic to SAOS-2 cells. However, as passivation proceeded, cytocompatibility was significantly increased from day 3 onward. Zn2+ ion release peaked at 24 h and declined significantly from day 2 to day 10. Compared to the other Zn alloys, ZnAgCuMn exhibited the lowest cytocompatibility. Most intriguingly, 3-month surfaces exhibited reduced cytocompatibility to osteoblasts compared to freshly polished samples. The observed in vitro cytotoxicity motivates further investigation of as-printed and post-processed L-PBF-manufactured Zn alloys, aiming to develop novel surface modification strategies to mitigate the initial ion burst responsible for reduced cytocompatibility and to adjust and tailor the overall degradation kinetics to physiologically tolerable levels tailored to the intended clinical application. Full article
(This article belongs to the Special Issue Biocompatible Research of Materials in Biomedical Applications)
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23 pages, 2021 KB  
Review
Calcium Phosphate Bone Substitutes in the Prevention of Bisphosphonate-Related Osteonecrosis of the Jaw: A Review
by Siri Paulo, Ana Margarida Abrantes, Mafalda Laranjo, Carlos Miguel Marto, Anabela Paula, Pedro Trancoso, Filomena Botelho, Arménio Serra and Manuel Marques Ferreira
J. Funct. Biomater. 2026, 17(3), 145; https://doi.org/10.3390/jfb17030145 - 16 Mar 2026
Viewed by 1289
Abstract
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is characterized by exposed necrotic bone that often progresses with increasing pain and impaired quality of life. Zoledronate, the most potent and widely used bisphosphonate, has been strongly associated with BRONJ development following invasive dental procedures. Given [...] Read more.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is characterized by exposed necrotic bone that often progresses with increasing pain and impaired quality of life. Zoledronate, the most potent and widely used bisphosphonate, has been strongly associated with BRONJ development following invasive dental procedures. Given the rising incidence of BRONJ, understanding and implementing effective preventive strategies have become imperative. Biomaterials based on synthetic hydroxyapatite and beta-tricalcium phosphate have been investigated as potential preventive agents. Their therapeutic rationale is supported by two key principles: the well-documented chemical interaction of calcium phosphates with bisphosphonates when used as drug carriers, and the established clinical use of synthetic calcium phosphate biomaterials in dentistry for bone regeneration. This review examines the underlying mechanisms of this preventive therapeutic strategy and evaluates studies investigating synthetic calcium phosphate biomaterials for BRONJ prevention through zoledronate adsorption at jaw wound sites, thereby reducing soft tissue toxicity and promoting healing. The evidence supports the protective effect of these biomaterials as a scientifically grounded preventive approach for BRONJ. Full article
(This article belongs to the Section Dental Biomaterials)
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25 pages, 18417 KB  
Article
Design and Performance Evaluation of TPMS-Based Dual-Layer Gradient Porous Structures for Bone Scaffolds
by Xiaobing Li, Donglai Zhou, Cuiyuan Lu, Min Zhong, Xianda Xie, Linyu Zhou and Yanghan Fu
J. Funct. Biomater. 2026, 17(3), 144; https://doi.org/10.3390/jfb17030144 - 13 Mar 2026
Cited by 1 | Viewed by 1322
Abstract
This study investigates and compares properties of various P-type Triply Periodic Minimal Surface (TPMS) porous structures for bone scaffold design. At first, six cases of homogeneous single/dual-layer structures, axial single/dual-layer gradient structures and radial single/dual-layer gradient structures with the same average porosity are [...] Read more.
This study investigates and compares properties of various P-type Triply Periodic Minimal Surface (TPMS) porous structures for bone scaffold design. At first, six cases of homogeneous single/dual-layer structures, axial single/dual-layer gradient structures and radial single/dual-layer gradient structures with the same average porosity are developed. Dual-layer gradient structures are selected for further design due to more similar pore and stress distributions to human bones, reduced maximum stress, higher yield strength and greater variations in yield strength and elastic modulus (E). The mechanical and permeability properties of ten cases of axial and radial dual-layer gradient structures with the same overall porosity but different inner and outer layer porosities are then further designed and studied. The results show that yield strength is within 112.75–139.97 MPa, E ranges from 11.15 to 13.01 GPa, the permeability (K) falls within 1.51–10.01 × 10−9 m2 and the average wall shear stress (WSSavg) varies between 6.18 and 9.11 mPa. The yield strength, E and K of radial dual-layer gradient structures are higher and WSSavg is lower than those of axial dual-layer gradient structures. Moreover, with increase in inner average porosity (P¯) and decrease in outer P¯, the yield strength, E and K gradually decrease while WSSavg gradually increases for both types of structures. In particular, the radial dual-layer structure with the lowest porosity of 27.5% in the inner layer and highest porosity of 42.5% in the outer layer has superior mechanical and permeability properties. The findings offer direct guidance for the structural design of bone implants, enabling performance customization for different applications. Full article
(This article belongs to the Section Bone Biomaterials)
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22 pages, 378 KB  
Review
Three-Dimensional Printing of a Spinal Interbody: Design Principles, Biomaterials, and Translational Considerations
by Sahil Garg, Patrick Young, Christopher Franquemont, Rachel Conley and Sanjitpal Gill
J. Funct. Biomater. 2026, 17(3), 143; https://doi.org/10.3390/jfb17030143 - 12 Mar 2026
Cited by 1 | Viewed by 1862
Abstract
Background: Interbody spinal fusion is a common surgical treatment for degenerative, traumatic, and deformity-related spinal pathologies. Despite advances in cage geometry and fixation strategies that improve alignment and early stability, reliable fusion remains limited by the mechanical and biological constraints of conventional interbody [...] Read more.
Background: Interbody spinal fusion is a common surgical treatment for degenerative, traumatic, and deformity-related spinal pathologies. Despite advances in cage geometry and fixation strategies that improve alignment and early stability, reliable fusion remains limited by the mechanical and biological constraints of conventional interbody implant materials. Traditional titanium and polymer-based cages often fail to optimally balance load sharing, osteointegration, and biological activity within the mechanically demanding interbody environment. This narrative review examines the development and translational potential of 3D-printed interbody fusion devices, with emphasis on how additive manufacturing enables the integration of mechanical performance with biologically active scaffold design. Methods: A thorough literature review was performed to evaluate the evolution, design principles, material properties, and translational outcomes of three-dimensional (3D)-printed interbody fusion devices. Results: Additive manufacturing enables precise control over implant architecture, allowing for the fabrication of porous, lattice-based cages with tunable stiffness, optimized load sharing, and enhanced bone–implant integration. Preclinical and early clinical studies suggest that 3D-printed porous titanium cages may reduce subsidence, promote osteointegration, and improve fusion-related outcomes compared with conventional designs. Emerging evidence indicates that scaffold porosity, surface microtopography, and bioactive coatings influence macrophage polarization, angiogenesis, and osteogenic signaling. Polymeric and composite constructs, particularly hybrid designs incorporating surface functionalization, represent promising adjuncts, though clinical evidence remains limited. Conclusions: Three-dimensional printing represents a paradigm shift in interbody fusion device design. Continued translational research and longer-term clinical follow-up are required to validate efficacy and guide widespread clinical adoption. Full article
(This article belongs to the Special Issue Advanced Biomaterials for Bone Tissue Engineering)
19 pages, 877 KB  
Review
Therapeutic Biomaterials for Chronic Osteomyelitis: Time–Space–Control Strategies for Infection Control and Bone Repair—A Narrative Review
by Jinqiu Tian, Qi Meng and Peixun Zhang
J. Funct. Biomater. 2026, 17(3), 142; https://doi.org/10.3390/jfb17030142 - 12 Mar 2026
Cited by 2 | Viewed by 2577
Abstract
Chronic osteomyelitis and infected bone defects are driven by recurrent infection, biofilm persistence, and dysregulated inflammation, but conventional “eradicate bacteria and fill the defect” approaches often fail to restore a regenerative microenvironment. Herein, we review biofilm-associated immune dysfunction in impaired angiogenesis/osteogenesis and summarize [...] Read more.
Chronic osteomyelitis and infected bone defects are driven by recurrent infection, biofilm persistence, and dysregulated inflammation, but conventional “eradicate bacteria and fill the defect” approaches often fail to restore a regenerative microenvironment. Herein, we review biofilm-associated immune dysfunction in impaired angiogenesis/osteogenesis and summarize biomaterials that couple infection control with tissue regeneration. We integrate representative platforms into a “Time–Space–Control” framework: (i) time-programmed systems that sequence early antibiofilm/antibacterial actions with later pro-angiogenic and osteogenic cues; (ii) space-focused designs that enhance defect localization, penetration, and coverage of infected niches; and (iii) controllable strategies that enable pathology-responsive and/or externally triggered, on-demand modulation. Based on this synthesis, we propose a practical 4P principle to guide programmable therapeutic biomaterials. Overall, explicitly managing timing, localization, and controllability may improve the alignment of antimicrobial therapy, immune reprogramming, and regenerative support for chronic infected bone repair. Full article
(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)
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14 pages, 2503 KB  
Article
A Defined-Area Bonding Approach for Microtensile Testing: A Reliable Alternative to Monoblock Sectioning for High-Hardness Restorative Materials
by Koji Yamashita, Chiharu Kawamoto, Yu Toida, Shimpei Kawano, Shuhei Hoshika, Hidehiko Sano and Atsushi Tomokiyo
J. Funct. Biomater. 2026, 17(3), 141; https://doi.org/10.3390/jfb17030141 - 11 Mar 2026
Viewed by 1013
Abstract
Background: The microtensile bond strength (μTBS) test is the gold standard for evaluating adhesive performance in restorative dentistry. However, the conventional non-trimming technique—referred to in this study as the monoblock sectioning technique (MST)—is difficult to apply to hard and brittle CAD/CAM materials such [...] Read more.
Background: The microtensile bond strength (μTBS) test is the gold standard for evaluating adhesive performance in restorative dentistry. However, the conventional non-trimming technique—referred to in this study as the monoblock sectioning technique (MST)—is difficult to apply to hard and brittle CAD/CAM materials such as zirconia and ceramics, thereby limiting test reproducibility. This study compared a newly developed defined-area bonding (DAB) method with MST to determine whether DAB could serve as a reliable specimen preparation technique for μTBS testing. Methods: CAD/CAM resin blocks and resin core materials were bonded using either ESTECEM II or Panavia V5. MST specimens were obtained by bonding the blocks first and subsequently sectioning them into individual beams. In contrast, DAB specimens were produced by pre-shaping the sticks and bonding them within a defined 1 mm2 area. μTBS, failure modes, and fracture/interface morphology (SEM) were evaluated. Results: MST produced significantly higher μTBS values than DAB (p < 0.001), with central MST beams showing the highest bond strengths. DAB values were statistically equivalent to MST peripheral values for both cements. More than 80% of failures were cohesive within resin cement across all groups. SEM revealed uniform cement layer thickness (50–60 μm) and similar peripheral-like fracture patterns in DAB specimens. Conclusions: Although MST yielded higher μTBS overall, the DAB method produced bond strengths equivalent to the MST peripheral region and demonstrated consistent fracture characteristics. Because DAB requires minimal cutting, it offers a promising, reproducible approach for μTBS testing of high-hardness materials that are otherwise difficult to section. Full article
(This article belongs to the Special Issue Biomaterials for Dental Reparative and Regenerative Therapies)
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23 pages, 19318 KB  
Article
Single-Step Extrusion Printing of Microgrooved Annulus Fibrosus Scaffolds via Patterned Nozzles
by Nadine Kluser, Gion Ursin Alig, Christoph Sprecher, Xavier Woods, Sibylle Grad, Mauro Alini, Sonja Häckel, Christoph E. Albers, David Eglin, Rajkishen Narayanan and Andrea J. Vernengo
J. Funct. Biomater. 2026, 17(3), 140; https://doi.org/10.3390/jfb17030140 - 11 Mar 2026
Viewed by 1082
Abstract
Intervertebral disk pathology, including disk herniation and degeneration, is a major contributor to chronic low back pain, and when conservative treatment fails, surgical management often involves discectomy-based procedures that leave residual annulus fibrosus (AF) defects associated with reherniation and progressive degeneration. These limitations [...] Read more.
Intervertebral disk pathology, including disk herniation and degeneration, is a major contributor to chronic low back pain, and when conservative treatment fails, surgical management often involves discectomy-based procedures that leave residual annulus fibrosus (AF) defects associated with reherniation and progressive degeneration. These limitations have motivated interest in regenerative strategies using biomaterial scaffolds; however, reproducing the hierarchical, angle-ply architecture of the AF remains challenging. Here, we present a single-step extrusion-based 3D-printing approach to fabricate polycaprolactone (PCL) scaffolds with aligned microscale surface grooves that promote AF-like organization. Patterned nozzles with circumferential peaks generated uniaxial concave microgrooves (10–17 µm wide) directly during printing, enabling formation of multilamellar angle-ply constructs. Human bone marrow-derived mesenchymal stem cells cultured on patterned scaffolds aligned longitudinally within concave grooves, forming end-to-end arrays that guided extracellular matrix deposition. Gene expression analysis showed that topographical cues governed cellular organization without significantly altering gene expression profiles, while TGF-β3 supplementation upregulated outer AF-associated markers, including COL1, COL12, SFRP2, MKX, MCAM, and SCX. TAGLN expression increased specifically on patterned scaffolds in the absence of TGF-β3, indicating an association between microgroove-guided cellular organization and TAGLN expression, warranting further investigation into potential tension-related mechanisms. This novel single-step extrusion-printing approach leverages custom nozzle geometry to impart concave microgrooves, facilitating scalable fabrication of multilamellar angle-ply scaffolds that induce aligned cellular organization and support potential applications in annulus fibrosus repair, as well as mechanobiological studies of anisotropic musculoskeletal tissues. Full article
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18 pages, 2261 KB  
Article
Cyclic Acidic Beverage Exposure Induces Formulation-Dependent Mechanical Softening and Tribological Alterations in Microhybrid and Nanohybrid Dental Resin Composites
by Żaneta Anna Mierzejewska, Patrycja Wołosiewicz, Kamila Łukaszuk, Bartłomiej Rusztyn, Jan Borys and Bożena Antonowicz
J. Funct. Biomater. 2026, 17(3), 139; https://doi.org/10.3390/jfb17030139 - 11 Mar 2026
Viewed by 1075
Abstract
Dental resin composites are routinely exposed to chemically aggressive beverages that may compromise long-term functional performance. This study investigated the structure–property–tribology relationships of four restorative composites (Filtek Z250, Filtek Z550, Herculite, and Herculite Ultra) subjected to cyclic immersion in beverages with different pH [...] Read more.
Dental resin composites are routinely exposed to chemically aggressive beverages that may compromise long-term functional performance. This study investigated the structure–property–tribology relationships of four restorative composites (Filtek Z250, Filtek Z550, Herculite, and Herculite Ultra) subjected to cyclic immersion in beverages with different pH values. A total of 120 cylindrical specimens (7 mm diameter, 2 mm thickness; n = 5 per material per condition) were fabricated and exposed to mineral water, tea, coffee, Coca-Cola®, Cola Light®, and red wine for 28 days under cyclic conditions. Microhardness, surface roughness (Ra), steady-state coefficient of friction (COF), and mass variation were evaluated. All composites exhibited significant microhardness reduction after acidic exposure (p < 0.05), with the greatest decrease observed for Herculite Ultra in red wine (−47.4%) and Coca-Cola® (−35.3%). Filtek Z250 demonstrated the highest baseline hardness and the lowest degradation susceptibility. Surface roughness changes were formulation-dependent, with Herculite Ultra showing pronounced roughening (ΔRa up to +0.074 µm), whereas Filtek Z550 exhibited erosion-driven smoothing (ΔRa down to −0.068 µm). Tribological behaviour was primarily governed by matrix softening rather than roughness alterations, with softened systems displaying unstable frictional responses (COF range: 0.127–0.697; p < 0.05). The results indicate that polymer matrix stability plays a more critical role in long-term functional performance than surface roughness or mass variation alone. Clinically, frequent exposure to acidic and solvent-containing beverages may accelerate mechanical and tribological degradation of susceptible composite formulations. Full article
(This article belongs to the Special Issue Biomaterials in Dentistry: Current Status and Advances)
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17 pages, 2298 KB  
Article
Differential Response of Stro-1+ and Stro-1 Shed to Er,Cr:YSGG Laser Stimulation: Viability, Matrix Production and Lineage Commitment
by Zornitsa Mihaylova, Marina Miteva, Emilia Karova, Natalia Grancharova, Violeta Dogandzhiyska, Mirela Marinova-Takorova, Krasimir Hristov, Vanyo Mitev, Evgeniy Aleksiev, Dimitar Kosturkov, Nadezhda Mitova, Irina Tsenova-Ilieva and Nikolay Ishkitiev
J. Funct. Biomater. 2026, 17(3), 138; https://doi.org/10.3390/jfb17030138 - 10 Mar 2026
Viewed by 775
Abstract
Stem cell heterogeneity represents a critical yet underexplored variable in laser-assisted regenerative strategies. While photobiomodulation has been shown to influence mesenchymal stem cell (MSC) behavior, it remains unclear whether stem cell maturation status modulates responsiveness to Er,Cr:YSGG irradiation. This study investigated the differential [...] Read more.
Stem cell heterogeneity represents a critical yet underexplored variable in laser-assisted regenerative strategies. While photobiomodulation has been shown to influence mesenchymal stem cell (MSC) behavior, it remains unclear whether stem cell maturation status modulates responsiveness to Er,Cr:YSGG irradiation. This study investigated the differential response of magnetically separated STRO-1+ and STRO-1 SHED subpopulations to low-power Er,Cr:YSGG laser stimulation (0.10 W and 0.25 W), focusing on viability, extracellular matrix production, and lineage commitment. STRO-1+ cells comprised 13.4% ± 1.2% of the total Stem Cells from Human Exfoliated Deciduous teeth (SHED) population. Laser exposure did not impair metabolic activity in either subpopulation. Collagen synthesis demonstrated a power- and time-dependent increase, with maximal enhancement observed in STRO-1+ cells at 0.25 W after 7 days. Laser irradiation selectively promoted osteogenic differentiation, as evidenced by increased alkaline phosphatase (ALP) expression at 0.10 W and enhanced mineral deposition, while chondrogenic potential remained unaffected and adipogenesis was reduced following 0.10 W exposure. These findings suggest that ALP expression is temporally and power-dependently modulated during osteogenic progression. Overall, Er,Cr:YSGG photobiomodulation does not uniformly affect heterogeneous SHED populations but modulates lineage allocation and extracellular matrix deposition in a maturation- and power-dependent manner. Integrating stem cell subpopulation selection with laser-based bioactivation may represent a strategy to refine regenerative endodontic and biomaterial-guided therapies. Full article
(This article belongs to the Special Issue Biomechanical Studies and Biomaterials in Dentistry (2nd Edition))
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12 pages, 1137 KB  
Article
Development of Freeze-Dried Hyaluronic Acid Sheets for Healing Oral Mucositis: Influence of Hyaluronic Acid Molecular Weight and Nicotinamide Mononucleotide Loading on Healing Efficacy
by Akiko Tanaka, Takanobu Takata, Hidemasa Katsumi, Yasuhisa Sawai, Hiroyuki Nakano, Chika Yoneto, Kunio Yoneto, Tomoyuki Furubayashi and Toshiyasu Sakane
J. Funct. Biomater. 2026, 17(3), 137; https://doi.org/10.3390/jfb17030137 - 10 Mar 2026
Viewed by 1289
Abstract
Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This [...] Read more.
Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This study aimed to optimize the HA sheet formulation by evaluating the effects of HA molecular weight and nicotinamide mononucleotide (NMN) loading on therapeutic efficacy. HA sheets were prepared using HA with four different molecular weights (50, 350, 800, and 2000 kDa), and their therapeutic effects were evaluated in an animal oral ulcer model using 6-week-old male Syrian hamsters. Among the formulations tested, the 800 kDa HA sheet exhibited the greatest healing efficacy, and it showed an excellent balance between buccal retention and the sustained release of NMN for the treatment of oral mucositis. In vitro cytotoxicity assays confirmed that HA, with or without NMN, was non-toxic and suitable for local applications. These findings indicate that HA sheets, particularly those composed of 800 kDa HA, may represent a promising and biocompatible mucoadhesive material for the delivery of NMN and the local treatment of oral mucositis associated with head and neck cancer. Full article
(This article belongs to the Special Issue 15th Anniversary of JFB—Advanced Biomaterials for Drug Delivery)
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23 pages, 2254 KB  
Article
Tribological Performance of CAM-Processed Interim Dental Restoration Materials: Effects of 3D Printing, Milling, and Post-Processing on Wear and Surface Topography
by Liliana Porojan, Roxana Diana Vasiliu, Flavia Roxana Bejan, Mihaela Ionela Gherban, Diana Uțu and Anamaria Matichescu
J. Funct. Biomater. 2026, 17(3), 136; https://doi.org/10.3390/jfb17030136 - 10 Mar 2026
Viewed by 1099
Abstract
In order to provide clinically significant evidence on the long-term functional performance of CAD/CAM provisional materials, especially 3D-printed and milled resins, accurate tribologically in vitro wear tests that integrate wear parameters and surface topography analysis are necessary. The goal of the study was [...] Read more.
In order to provide clinically significant evidence on the long-term functional performance of CAD/CAM provisional materials, especially 3D-printed and milled resins, accurate tribologically in vitro wear tests that integrate wear parameters and surface topography analysis are necessary. The goal of the study was to assess the wear resistance of several CAM-obtained dental crown materials and the relationship between wear and the manufacturing process, distinctive postprocessing, microhardness, microroughness, and surface topography. A standardized ball-on-flat tribological protocol was applied to (n = 70) CAD/CAM-fabricated PMMA specimens (four 3D-printed groups with distinct post-processing protocols (Optiprint) and three milled materials (TelioCAD, Shaded PMMA, Copra Temp Symphony)) to quantify wear parameters micro- and nanoroughness (Ra, Rz, Sa, Sy), and Vickers microhardness, followed by comprehensive statistical analysis (t-tests, Pearson correlations) to elucidate material- and process-dependent differences in wear behaviour. Nanoroughness was carried using atomic force microscopy evaluation. Wear testing showed that most materials, particularly the 3D-printed groups, developed limited wear, whereas the milled materials evolved toward groove-dominated wear topographies. Wear statistics showed that the printed resins consistently had an advantage, meaning that the degree and rate of wear are significantly influenced by the manufacturing process. Hardness has a central role in governing the wear performance of interim resin materials, while nanoroughness acts as a secondary factor. Optimised post-processing of printed materials, particularly a prolonged post-curing period, yields a beneficial combination of low wear and specific topography, thereby providing a significant clinical advantage. Full article
(This article belongs to the Section Dental Biomaterials)
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25 pages, 2126 KB  
Review
Living Tissues by Design: The Rise of Hybrid Models in Biofabrication
by Varvara Platania, Argyro Lamprou and Isaac Maximiliano Bugueno
J. Funct. Biomater. 2026, 17(3), 135; https://doi.org/10.3390/jfb17030135 - 10 Mar 2026
Cited by 2 | Viewed by 1495
Abstract
Current in vitro tissue models struggle to recapitulate the structural, vascular, and mechanical complexity of human tissues, limiting their physiological relevance for disease modelling and preclinical testing. Self-organising three-dimensional cultures such as spheroids and organoids capture key aspects of cellular organisation and differentiation, [...] Read more.
Current in vitro tissue models struggle to recapitulate the structural, vascular, and mechanical complexity of human tissues, limiting their physiological relevance for disease modelling and preclinical testing. Self-organising three-dimensional cultures such as spheroids and organoids capture key aspects of cellular organisation and differentiation, but they commonly lack controlled geometry, perfusable vasculature, and reproducible mechanical microenvironments. Conversely, biofabrication strategies, such as three-dimensional (3D) bioprinting and organ-on-chip (OoC) microfluidic devices, offer spatial control, integrated perfusion, and dynamic mechanical stimulation, yet often fall short in recapitulating the full cellular diversity and self-organisation of native tissues. Notably, emerging hybrid approaches that embed self-organising biological units (e.g., organoids and spheroids) into engineered scaffolds or microfluidic platforms combine biological relevance, architectural fidelity, and functional control. Advances in bioink chemistry, sacrificial-printing vascularisation, and chip–organoid interfaces now enable perfusable, multicompartment tissues suitable for disease modelling and preclinical testing. This review highlights the most recent (2020–2025) progress in organoid vascularisation, bioprinting strategies for prevascularised constructs, and OoC integration, outlining remaining challenges and emphasising priorities for next-generation hybrid cellular and tissue models. Full article
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17 pages, 5905 KB  
Article
LHRH-Conjugated Magnetite Nanoparticles and Nanorods as Magnetic Resonance Imaging Contrast Agents for Targeting Triple-Negative Breast Cancer
by Chukwudi C. Ezeala, John D. Obayemi, Ali A. Salifu, Theresa Ezenwafor, Yiporo Danyuo, Maria Chinyerem Onyekanne, Stanley C. Eluu, Toyin Aina, Josephine Oparah, Precious O. Etinosa, Olushola S. Odusanya and Winston O. Soboyejo
J. Funct. Biomater. 2026, 17(3), 134; https://doi.org/10.3390/jfb17030134 - 10 Mar 2026
Viewed by 891
Abstract
This paper presents the results of an experimental study on the effects of magnetite nanoparticle (MNP) shape on magnetic resonance imaging (MRI) of triple-negative breast cancer (TNBC) xenograft tissues. T2-weighted MRI scans using spherical shaped MNPs as contrast agents are compared [...] Read more.
This paper presents the results of an experimental study on the effects of magnetite nanoparticle (MNP) shape on magnetic resonance imaging (MRI) of triple-negative breast cancer (TNBC) xenograft tissues. T2-weighted MRI scans using spherical shaped MNPs as contrast agents are compared to MRI scans done with nanorod-shaped MNPs as contrast agents. The MNPs were first coated with polyethylene glycol (PEG) and subsequently conjugated to luteinizing hormone-releasing hormone (LHRH) to specifically target LHRH receptors, which are present at high levels on the surfaces of xenograft TNBC cells/tissues. After 3 weeks of tumor growth in nude immunocompromised mice, LHRH-conjugated (functionalized) and unconjugated (non-functionalized) MNPs were injected into the immunocompromised mice. Four types of MNPs were used: non-functionalized nanorod-shaped MNPs (BMNR); LHRH-conjugated nanorod-shaped MNPs (LCMNR); non-functionalized spherical-shaped MNPs (BSSMNP); and LHRH-conjugated spherical-shaped MNPs (LCSSMNP). T2-weighted magnetic resonance imaging (MRI) scans were obtained from the mice before the injection of the MNPs and two hours after the injection of the MNPs. The results show that using nanorod-shaped LHRH-conjugate MNPs as contrast agents yielded higher-resolution T2-weighted MRI scans of TNBC tumors compared to those from spherical-shaped MNPs. The implications of the results are discussed in relation to potential applications of functionalized MNPs in MRI for TNBC diagnosis. Full article
(This article belongs to the Special Issue Development of Nanomaterials for Imaging, Diagnosis and Therapy)
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39 pages, 4776 KB  
Article
Influence of Treated Surface Proportion on the Antibacterial Performance of UV-Activated Hydroxyapatite–Magnesium Phosphate–Zinc Oxide Coating on Magnesium Alloys
by Purificación Tamurejo-Alonso, Juan Manuel Casares-López, Federico Rafael García-Galván, Juan Antonio Constantino, Amparo M. Gallardo-Moreno, Juan Carlos Galván, Miguel Ángel Pacha-Olivenza and M. Luisa González-Martín
J. Funct. Biomater. 2026, 17(3), 133; https://doi.org/10.3390/jfb17030133 - 9 Mar 2026
Viewed by 1439
Abstract
Surface damage occurring during surgery can compromise coating integrity, leaving exposed areas susceptible to bacterial colonization. However, the impact of partial coating loss on antibacterial performance has not yet been investigated. In this work, a multifunctional UV-activated coating composed of hydroxyapatite, magnesium phosphate, [...] Read more.
Surface damage occurring during surgery can compromise coating integrity, leaving exposed areas susceptible to bacterial colonization. However, the impact of partial coating loss on antibacterial performance has not yet been investigated. In this work, a multifunctional UV-activated coating composed of hydroxyapatite, magnesium phosphate, and zinc oxide (HMZ) was developed and electrodeposited onto AZ31 and MgCa magnesium alloys. Its antibacterial efficacy against Staphylococcus aureus and Escherichia coli was evaluated under three conditions: adhered bacteria, planktonic cells, and biofilm. In the absence of UV activation, coated surfaces exhibited no significant antibacterial activity. In contrast, fully coated and UV-activated surfaces achieved bacterial reductions above 98% in all scenarios. Surfaces with 60% coverage showed antibacterial efficacy equivalent to that of fully coated surfaces, even against established biofilm. Surfaces with 30% coverage also exhibited moderate activity, particularly against adhered and planktonic bacteria. These results demonstrate that full surface coverage is not required to preserve the coating’s antibacterial effectiveness. This strategy provides a clinically relevant solution to maintain antibacterial protection even when coating integrity is compromised. Full article
(This article belongs to the Section Antibacterial Biomaterials)
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12 pages, 1836 KB  
Article
Influence of the Topography of Zirconium Treated with Laser Micropatterning on Periodontal Ligament Stem Cells: An In Vitro Study
by Ildefonso Serrano-Belmonte, Alba Rico-Molina, Juan Ignacio Rosales-Leal, Guillermo Lorite-Méndez, Miguel Ángel Rodríguez-Valverde, Clara Serna-Muñoz and Ascensión Martínez-Cánovas
J. Funct. Biomater. 2026, 17(3), 132; https://doi.org/10.3390/jfb17030132 - 9 Mar 2026
Cited by 1 | Viewed by 770
Abstract
Zirconium is a widely used material in the field of dentistry, employed for implants and their components as well as for the creation of crowns and veneers. Given that its biocompatibility has been studied and demonstrated in various fields of application, it is [...] Read more.
Zirconium is a widely used material in the field of dentistry, employed for implants and their components as well as for the creation of crowns and veneers. Given that its biocompatibility has been studied and demonstrated in various fields of application, it is necessary to analyze how surface modification of this material influences its properties. The purpose of this study was to analyze the biocompatibility, initial adhesion (48 h), and morphology of periodontal ligament stem cells (PDLSCs) seeded on different zirconium surfaces treated with laser micropatterning, as well as plastic coverslips as a control. The Neubauer chamber was used to count the cells adhered to each of the sets, and confocal and scanning electron microscopy were employed to examine the adhesion and morphology of periodontal ligament stem cells on each of the zirconium surfaces studied. Results: Statistically significant differences were found in terms of primary cell adhesion, with sets 3 (grid topography) and 4 (channel topography) showing the most favorable characteristics for fibroblast adhesion. It was concluded that regular and moderately rough surfaces promoted better cell proliferation and development. Full article
(This article belongs to the Special Issue Advances in Biomaterials for Oral and Dental Tissue Engineering)
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16 pages, 1221 KB  
Article
Evaluation of the Physicochemical and Biological Properties of Calcium-Silicate-Based Root-End Filling Materials
by Asuka Aka, Takashi Matsuura and Atsutoshi Yoshimura
J. Funct. Biomater. 2026, 17(3), 131; https://doi.org/10.3390/jfb17030131 - 9 Mar 2026
Cited by 2 | Viewed by 1112
Abstract
This study compared the physicochemical and biological properties of Bio-C Repair (BR), a new putty-type calcium silicate-based material, with ProRoot MTA (P) and Super-Bond (SB). Discs of the three materials were prepared. Human periodontal ligament cells were seeded onto the discs, and metabolic [...] Read more.
This study compared the physicochemical and biological properties of Bio-C Repair (BR), a new putty-type calcium silicate-based material, with ProRoot MTA (P) and Super-Bond (SB). Discs of the three materials were prepared. Human periodontal ligament cells were seeded onto the discs, and metabolic activity was assessed by MTT assay on days 7 and 28; cells without discs served as the negative control (NC). Moreover, the pH and calcium ion concentration of the eluate, the mass change, and the water sorption were investigated. On day 7, BR showed significantly lower cell activity than P and NC. However, by day 28, BR activity increased significantly, with no significant difference relative to other groups, whereas P activity was significantly suppressed relative to SB and NC. Physiochemically, BR maintained a significantly higher alkalinity (pH ~11.0) and greater calcium ion release than P throughout the 28 days. Furthermore, BR exhibited significant mass gain (15.7%) and the highest water sorption (15.4%), whereas P showed mass loss (−1.1%). Although the high pH of BR initially suppressed cell activity, it demonstrated favorable cytocompatibility by day 28. BR showed a significantly improved long-term cellular response compared to P, suggesting it is a promising alternative as a root-end filling material. Full article
(This article belongs to the Special Issue Advanced Biomaterials and Engineered Systems in Endodontics)
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14 pages, 847 KB  
Article
From Lab to Chairside: Dentists’ Perception of Natural Nanomaterials and Smart Delivery Systems in Regenerative Dentistry
by Dana Emanuela Cot (Pitic), Andreea-Mihaela Kis, Diana Marian, Muntean Călin, Radu Dumitru Moleriu, Lavinia Cristina Moleriu, Adina Feher, Laria Maria Trușculescu, Aura Mara Bodnar and Ramona Amina Popovici
J. Funct. Biomater. 2026, 17(3), 130; https://doi.org/10.3390/jfb17030130 - 9 Mar 2026
Viewed by 811
Abstract
Background: The clinical translation of natural nanomaterials and smart delivery systems in regenerative dentistry relies heavily on practitioner acceptance; however, end-user perspectives remain under-investigated. Objective: This study evaluated dental practitioners’ self-reported knowledge, attitudes, and perceived barriers regarding these innovations. The questionnaire examined stated [...] Read more.
Background: The clinical translation of natural nanomaterials and smart delivery systems in regenerative dentistry relies heavily on practitioner acceptance; however, end-user perspectives remain under-investigated. Objective: This study evaluated dental practitioners’ self-reported knowledge, attitudes, and perceived barriers regarding these innovations. The questionnaire examined stated intention and self-reported willingness, not clinical behaviour. Methods: A cross-sectional survey using convenience sampling was conducted among 713 Romanian dentists. Statistical analysis included Chi-square tests and odds ratio estimation to identify factors associated with willingness to adopt nano-formulations. Results: Self-reported familiarity was moderate, with only 19.1% of respondents describing themselves as “very familiar” with nanodentistry; nevertheless, 77.3% believed natural nano-formulations could match synthetic efficacy. High costs (36.5%), lack of long-term evidence (35.9%), and staining concerns (46.0%) were identified as primary perceived barriers. Experience with digital technologies (CAD/CAM) was significantly associated with a positive attitude toward adoption (OR = 2.05, 95% CI: 1.41–2.98, p < 0.001). Conclusions: Respondents demonstrated a generally positive attitude toward integrating bioactive nanomaterials, though widespread adoption is currently limited by economic, educational, and evidentiary gaps. Future strategies should focus on establishing clear clinical protocols, providing robust long-term safety data, and improving the aesthetic stability of natural biomaterials. Full article
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24 pages, 375 KB  
Review
Next-Generation Orthodontics: Functional Resins, Biomechanics, Biocompatibility, and Current Clinical Reality of Direct 3D-Printed Aligners
by Yulong Zhang and Benjamin M. Wu
J. Funct. Biomater. 2026, 17(3), 129; https://doi.org/10.3390/jfb17030129 - 9 Mar 2026
Cited by 3 | Viewed by 2272
Abstract
The orthodontic landscape is currently witnessing a significant technological evolution with the emergence of direct 3D-printed aligners (DPAs), which promise to close the digital workflow loop by eliminating the geometric limitations and solid model waste inherent to traditional thermoformed clear aligners (TCAs). This [...] Read more.
The orthodontic landscape is currently witnessing a significant technological evolution with the emergence of direct 3D-printed aligners (DPAs), which promise to close the digital workflow loop by eliminating the geometric limitations and solid model waste inherent to traditional thermoformed clear aligners (TCAs). This review provides a comprehensive analysis of the material science governing this transition from inert thermoplastic sheets to reactive photocurable resins. We explore the fundamental chemistry of DPA materials, and the pivotal role of post-processing in ensuring mechanical integrity and biocompatibility. Beyond passive mechanics, this review highlights preclinical research in functional material engineering, detailing how experimental DPAs are being investigated for the integration of antibacterial agents, remineralization fillers, and drug delivery systems. Furthermore, we evaluate the limited but emerging clinical data on DPAs, contrasting their shape-memory properties and force delivery profiles with conventional appliances, while critically addressing emerging safety concerns regarding monomer elution and microplastic generation. We conclude that while DPA technology offers superior dimensional control, comprehensive life cycle assessments and long-term in vivo trials are essential to fully substantiate their clinical efficacy, overall sustainability, and potential as advanced orthodontic appliances. Full article
(This article belongs to the Special Issue Dental Biomaterials in Implantology and Orthodontics)
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