Journal of Functional Biomaterials最新文献

Background: This study aimed to evaluate the effects of tetracalcium phosphate (TTCP) graft material on the stability and osseointegration of dental implants placed in anatomically compromised bone.

Materials and methods: Six healthy sheep were used following ethical approval. Osteotomies were created in the tibial region and divided into three groups: Group A (control, n = 12) with standard osteotomy; Group B (n = 12) with enlarged and deepened osteotomy; and Group C (n = 36), where osteotomy sites were filled with TTCP prior to implant placement. Implant stability was measured using the resonance frequency analysis (RFA), and osseointegration was evaluated histologically by bone-to-implant contact percentage (BIC%). Animals were sacrificed at the 3rd and 6th weeks for histological analysis.

Results: Initial RFA values exceeded 42.5 in all groups. Group C demonstrated the highest RFA at Week 6 (79) and significantly higher RFA values at Week 3 compared to other groups, while Group B consistently showed the lowest stability. At Week 3, Group A exhibited the highest BIC% (28.04 ± 5.05%). By Week 6, BIC% increased in all groups, with no significant intergroup differences. Robust ANOVA revealed significant effects of time and group on both RFA and BIC%.

Conclusions: TTCP significantly enhanced implant stability and osseointegration in compromised bone, providing improved secondary stability and suggesting its potential clinical benefit in challenging anatomical conditions.

This study evaluated the bond strength of self-adhesive resin cement (SARC) containing 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and calcium silicate, with and without zirconia primer, before and after thermocycling. Sintered zirconia specimens (n = 180) were sequentially polished, sandblasted, and bonded with TheraCem (TC), Clearfil SA Luting (SA), or Rely X U200 (RU), with and without Z-Prime Plus primer. Specimens were stored in water at 37 °C or subjected to 10,000 thermocycles (5-55 °C). Shear bond strength (SBS), failure modes, fracture surfaces, flexural strength, and Vickers hardness were assessed. Bonding performance was governed by material-specific interactions rather than a complex three-factor interplay between resin cement type, primer application, and thermocycling. SBS followed the order TC > SA > RU and was significantly higher with primer application. Thermocycling significantly reduced SBS in all groups. Premature failure occurred in the RU and SA groups. Mixed failure was predominant across all conditions. The flexural strength and Vickers hardness were highest in the RU group, followed by the TC and SA groups, with RU maintaining significantly higher hardness even after thermocycling. Overall, SARCs containing MDP and calcium silicate demonstrated favorable bonding performance, which was further enhanced by zirconia primer application.

Large bone defects and loss present major orthopedic challenges. In preclinical research, femoral bone defects in rats are commonly used as in vivo models to evaluate new osteoregenerative biomaterials. These test items are typically compared to negative and positive controls. This review aims to summarize the different control groups used to evaluate new osteoregenerative test items in preclinical rat femoral defect models and to identify potential pitfalls related to these controls, ultimately to enhance the future translational success. The protocol for this review was registered in PROSPERO, and no specific funding was received for this work. The systematic search comprised publications between January 2001 and January 2023. 436 studies were included for analysis. The choice of control groups was inconsistent across studies. A negative (e.g., empty defects or inert carriers) and positive (e.g., bone grafts or commercially available bone substitutes) control group was included in 56% (n = 245/436) and 34% (n = 149/436) of the included studies, respectively. Notably, 25% (n = 109/436) of the studies did not include any control group. Bone grafts were used as positive controls in 50% of the studies that included positive controls (n = 74/149), mainly of allogeneic origin (45%, n = 33/74). The control groups used to evaluate the test item impacted the healing comparison, with 81% of studies showing better healing of their test items compared to negative control (n = 198/245) versus 54% compared to positive control (n = 80/149). A qualitative risk-of-bias and reporting assessment was performed using an integrated ARRIVE-SYRCLE framework. Most studies demonstrated moderate concern in several domains, with frequent absence of randomization (67%, high concern) and blinding (84%, high concern), incomplete reporting of inclusion/exclusion criteria (74%, moderate concern), and variable clarity regarding animal characteristics and statistical methodology. The variability in the choice of control groups appears to influence study outcomes. Inadequate control group selection can lead to misleading conclusions regarding the efficacy of new biomaterials. Therefore, standardizing control group selection is crucial to enhance the reliability and comparability of preclinical research findings.

Reliable vascular access remains a major clinical challenge for hemodialysis patients, as expanded polytetrafluoroethylene (PTFE) grafts exhibit poor patency and frequent complications driven by thrombosis and neointimal hyperplasia. Tissue-engineered vascular grafts offer a regenerative alternative but often lack the mechanical resilience required for high-flow arteriovenous (AV) environments. Here, we developed a reinforced, biofunctionalized coaxial electrospun graft comprising a poly(ε-caprolactone) mechanical core and a norbornene-functionalized poly(ethylene glycol) sheath incorporating pro-endothelialization cues. Circumferential PTFE rings were added to improve kink resistance. Grafts were implanted in a porcine AV configuration that recapitulates clinical hemodynamic conditions. Mechanical characterization included compliance, burst pressure, and kink resistance; host remodeling was assessed using histology, immunofluorescence, and multiphoton imaging at 4 weeks. Ring-reinforced electrospun grafts demonstrated a kink radius of 0.187 cm, compliance of 1.04 ± 0.29%/100 mmHg, and burst pressure of 1505 ± 565 mmHg, values all comparable to Gore-Tex PTFE and within industrial performance standards. In vivo, the electrospun grafts showed extensive host cell infiltration, collagen deposition, and formation of smooth muscle-like tissue, whereas PTFE controls remained largely acellular. Immunofluorescence confirmed intramural α-SMA⁺ and CD31⁺ cell populations, and multiphoton microscopy revealed significantly greater collagen and elastin content compared with PTFE (p < 0.05). Collectively, these findings demonstrate that the reinforced electrospun graft maintains mechanical integrity under physiological AV loading while supporting in situ endothelialization and extracellular matrix remodeling in a clinically relevant, large animal model. This work provides one of the first demonstrations of functional tissue regeneration within a fully synthetic, acellular scaffold in a porcine hemodialysis model and advances the translational development of durable, regenerative vascular access grafts that couple mechanical resilience with bioactive healing capacity.

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.

Hemostatic biomaterials are widely used in surgical and trauma settings, yet their influence on early wound healing remains incompletely understood. This in vivo study investigated the effects of cellulose- and gelatin-based hemostatic biomaterials on early wound healing using a murine skin wound model. Oxidized non-regenerated cellulose (ONRC), oxidized regenerated cellulose (ORC), and a porcine gelatin-based matrix (GELA) were left in situ following standardized subcutaneous implantation and compared with sham-treated controls. Tissue responses were analyzed at postoperative days 3 and 7 using histology, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR). Cellulose-based materials persisted as eosinophilic remnants, whereas fibrous matrix structures and enhanced extracellular matrix deposition were observed in the GELA group. Immunohistochemical analysis revealed increased cluster of differentiation 68 (CD68)-positive macrophage presence in the ORC group at day 3 and in the GELA group at day 7, indicating biomaterial-dependent modulation of macrophage involvement during early wound healing. Expression of Kiel 67 (Ki-67), a marker of cellular proliferation, was significantly elevated in the epidermis of the GELA group at day 7, suggesting enhanced proliferative activity during the reparative phase. In contrast, no significant differences were detected in the expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), or cluster of differentiation 14 (CD14) between groups. Overall, none of the investigated biomaterials impaired early wound healing, while the gelatin-based material demonstrated features consistent with enhanced reparative cellular responses without excessive inflammation.

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.

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.

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.

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.