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253


Improving fatigue resistance of translucent 4Y-PSZ zirconia through glass gradation

Souza, Felipe Machado; Alves, Larissa M M; Sousa, Edisa O; Campos, Tiago Moreira Bastos; Marcolino, Giovana Assis; Piza, Mariana Miranda de Toledo; Dias, Rainã S; Yamaguchi, Satoshi; Gierthmuehlen, Petra C; Witek, Lukasz; Coelho, Paulo G; Bonfante, Estevam A; Benalcazar-Jalkh, Ernesto B
To evaluate the effect of graded glass infiltration on the fatigue behavior and mechanical reliability of translucent 4Y-PSZ zirconia before and after hydrothermal aging, disc-shaped specimens were fabricated by uniaxial pressing and divided into control and glass-graded groups (n = 36/group). Glass infiltration was performed on pre-sintered specimens followed by final sintering, and half of the specimens from each group underwent hydrothermal aging (134°C, 2.2 bar, 20 h). Microstructure and phase composition were assessed by scanning electron microscopy and x-ray diffraction. Mechanical performance was evaluated using step-stress accelerated life testing, with Weibull statistics, reliability analysis, and inverse power-law modeling. Glass-graded specimens demonstrated higher reliability and characteristic strength (≈330 MPa increase) with similar Weibull modulus compared to controls. The inverse power-law parameter α0 was higher for the glass-graded group, indicating extended fatigue life, whereas comparable α1 values suggested similar life-stress relationships. Hydrothermal aging did not significantly affect mechanical performance, although phase transformation occurred in the control group. Fractography revealed surface-initiated failures in controls and interface-related crack initiation in glass-graded specimens. Graded glass infiltration improved the fatigue reliability and characteristic strength without compromising hydrothermal stability of 4Y-PSZ. These results suggest that glass-graded 4Y-PSZ may expand the clinical applicability of translucent zirconia for long-span (≥4-unit) prosthetic reconstructions.
PMID: 42076845
ISSN: 1600-0722
CID: 6030812

Comparative Histologic Evaluation of Bone Healing Following Piezotome and Osteotome Techniques for Potential Applications in Rhinoplasty

Munkwitz, Sara E; Iglesias, Nicholas J; Shah, Hana; Wu, Shangtao; Almada, Ricky; Nayak, Vasudev Vivekanand; Jabori, Sinan K; Thaller, Seth R; Witek, Lukasz; Coelho, Paulo G
Rhinoplasty is a technically demanding procedure in which the precision of osteotomy creation directly influences cosmetic and functional outcomes. Traditional osteotomes often produce uncontrolled fracture lines and soft tissue trauma. Piezoelectric devices have been introduced as an alternative. They offer selective cutting of mineralized tissue while sparing surrounding soft tissue structures. Although the clinical benefits of this approach have been well documented, the biological processes defining this technique remain unsettled. The current study aimed to compare the histological changes in bone regeneration and long-term healing outcomes within piezotome-induced and osteotome-induced nasal bone defects in a translational, preclinical ovine model. Bilateral osteotomies were created on the nasal bone of n=12 skeletally mature sheep using a piezoelectric bone-cutting system (Piezotome CUBE, Acteon) or a traditional osteotome. Euthanasia was performed at either 3 or 12 weeks postoperatively (6 defects per group per time point). Histological analysis at 3 weeks postoperatively revealed limited bone ingrowth, followed by substantial bone regeneration in both groups by 12 weeks. Osteotome-treated sites displayed irregular margins and bone debris, while piezotome-treated defects demonstrated cleaner margins and less bony fragmentation. Despite qualitative differences, semi-quantitative scoring of new bone formation showed no statistically significant differences in healing between devices at 3 weeks (p=0.500) or 12 weeks (p=0.125). These findings suggest that although piezoelectric osteotomies may offer advantages in intraoperative precision and early postoperative morbidity, long-term bone regeneration appears comparable to that achieved with conventional osteotomes.
PMID: 42189619
ISSN: 1536-3732
CID: 6070540

Evaluation of the fatigue behavior of implant-supported 3D-printed and milled resins for definitive crowns

Benalcázar-Jalkh, Ernesto B; Alves, Larissa M M; Campos, Tiago M B; Carvalho, Laura F; Silveira, Paulo E A; Gierthmuehlen, Petra C; Silva, Nelson R F A; Witek, Lukasz; Coelho, Paulo G; Yamaguchi, Satoshi; Speratti, Drauseo; Bonfante, Estevam A
OBJECTIVES/OBJECTIVE:To evaluate the reliability and failure modes of 3D-printed crowns fabricated from different resin composites compared to a milled resin composite block, all indicated as definitive restorations. METHODS:Four 3D-printing resins were evaluated: 1) CeramicCrown (CC; SprintRay), 2)VarseoSmile-Crown (VSC, Bego), 3) Crowntec (CRO, Saremco), and 4) Ceramage 3D-Printed (C3D, Shofu), along a milled resin-composite block: Shofu Block HC Super-Hard (SSH, Shofu). Eighteen implant-supported maxillary first-molar crowns were manufactured per group and tested under step-stress accelerated life testing. Weibull statistics were applied, and reliability was calculated for 100,000 cycles at different loads. Fractographic analysis was performed under scanning electron microscopy. RESULTS:All 3D-printed samples failed during fatigue testing, whereas SSH samples survived both the initial protocol and the extended cycling, in which the load profiles were modified to increase the number of cycles (up to 2400,000). Failures were related to material strength (C3D, CC, VSC) or fatigue damage accumulation (CRO). At a mission of 100,000 cycles at 300 N, all 3D printed groups presented high reliability (>99 %). Under higher loads (800-1000 N), CRO and VSC had lower reliability compared to C3D and CC. Characteristic fracture load was highest for C3D and CC, intermediate for CRO, and lowest for VSC. CRO showed the lowest Weibull modulus. Fractographic analysis indicated fracture initiation at the occlusal surface in printed crowns, propagating toward the margins and abutment. SSH crowns exhibited wear marks with no crack formation. SIGNIFICANCE/CONCLUSIONS:While the milled composite demonstrated superior fatigue resistance, 3D-printed definitive crowns exhibited material-dependent fatigue behavior. Among printed groups, CC and C3D presented higher characteristic fracture load and reliability under higher loads compared to CRO and VSC.
PMID: 41444092
ISSN: 1879-0097
CID: 6011102

Mechanosensitive Piezo1 Channels in Enamel Cells

Bomfim, Guilherme H Souza; Zou, Anna; Echeverry, Fabio A; Bui, Ai Thu; de Oliveira Sousa, Edisa; Graciliano Silva, Bruno Luis; Witek, Lukasz; Coetzee, William A; Lacruz, Rodrigo S
Ameloblasts are specialized epithelial cells that form enamel during the secretory and maturation stages, the latter involving an increase in Ca2+ transport to mineralize the enamel crystals. During enamel formation, ameloblasts travel several microns while secreting a matrix and are surrounded by several cell layers in the confined space of the enamel organ. Presumably, ameloblasts are subjected to mechanical stimuli e.g. pressure, stretch. Mechanosensitive (MS) or stretch-gated channels are expressed in the membranes of many cells including mineralizing cells. The opening of MS channels occurs in response to physical stimuli and results in the influx of ions. Piezo1 is a non-selective class of MS channel permeable to Ca2+ and hence it may contribute to Ca2+ homeostasis in ameloblasts. Here we show that secretory and maturation stage ameloblasts express similar protein levels of Piezo1. Cultured rat primary secretory and maturation stage ameloblasts showed stretch-activated currents by patch-clamp. Ameloblasts loaded with the cytosolic Ca2+ indicator Fura-2 were also stimulated with the Piezo1-selective activator Yoda1. We show that ameloblasts are sensitive to Piezo1 stimulation which evoked an increase in cytosolic Ca2+. This effect was inhibited by Piezo1 blockers. Mechanical analysis of the incisors of Piezo1 cKO mice showed no alterations in hardness or elastic modulus relative to littermate control mice. Our work provides the first evidence that Piezo1 channels are functional in both ameloblast stages and their activation leads to an elevation in cytosolic Ca2+, however, Piezo1 does not appear to be essential for enamel mineralization.
PMID: 42036588
ISSN: 1432-0827
CID: 6041412

The Influence of Non-Thermal Plasma Treatment on Osseointegration of Endosteal Implants Presenting Decompressing Vertical Chambers

Mehra, Shray; Shah, Hana; Munkwitz, Sara E; Iglesias, Nicholas J; Joshua, Tina; Tadisina, Kashyap K; Fullerton, Natalia; Nayak, Vasudev Vivekanand; Witek, Lukasz; Coelho, Paulo G
Current evidence suggests that achieving the desired level of osseointegration necessitates a hierarchical approach to implant design. This is particularly relevant for osseointegration around implant systems such as those presenting vertical decompression chambers and acid-etched surfaces which could further be augmented by non-thermal plasma (NTP) treatment. Three implant systems were compared in this study: (i) ND (GM Helix Acqua Implant; Neodent®, Curitiba, PR, Brazil-hybrid, acid-etched thread design treated with isotonic sodium chloride solution), (ii) Sin (Epikut Plus; S.I.N. Implant System, São Paulo, Brazil-V-shaped, acid-etched thread design treated with nano-hydroxyapatite), and (iii) Mp (Maestro; Implacil De Bortoli, São Paulo, Brazil-buttress, acid-etched thread design with decompressing vertical chambers). The ND and Sin implants were used directly as supplied by the manufacturer. For the Mp implants, the manufacturer-supplied surface was subjected to supplemental acid etching with 37% hydrochloric acid followed by Argon-based NTP treatment administered with a pulsed plasma generator prior to implantation into the iliac crest of n = 12 adult female sheep. Histomorphometric analysis was conducted at 3- and 12-week post-implantation (n = 6 sheep per time point) to assess bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). After 3 weeks in vivo, the healing chambers of all implant groups consisted predominantly of newly forming woven bone. By 12 weeks, bone maturation was observed, with the presence of remodeling sites and some areas of well-organized lamellar structures occupying the healing chambers. At both 3 and 12 weeks, the Mp implants demonstrated significantly higher BAFO values relative to ND (p = 0.015 and p = 0.008, respectively). The combination of vertical healing chambers, acid etching, and NTP treatment promoted early vascular infiltration and sustained bone deposition.
PMCID:13113549
PMID: 42072266
ISSN: 2306-5354
CID: 6030722

Bilayered Porcine Derived Collagen Membranes for Soft Tissue Augmentation in the Oral Cavity

Munkwitz, Sara E; Shah, Hana; Iglesias, Nicholas J; Slavin, Blaire V; Stauber, Zachary M; Costello, Joseph P; Nayak, Vasudev Vivekanand; Thaller, Seth R; Witek, Lukasz; Coelho, Paulo G
Soft tissue augmentation in the oral cavity is limited by mechanical loading, salivary enzymes, and rapid degradation of collagen-based biomaterials. Porcine-derived collagen membranes (PDCMs) may provide an alternative to autografts, but their clinical performance is influenced by membrane architecture, crosslinking, and the surgical environment. This study evaluated the long-term biocompatibility, degradation behavior, and soft tissue healing outcomes of two novel crosslinked PDCMs compared with an established noncrosslinked bilayer membrane in a canine mandibular defect model. Standardized full-thickness mandibular soft tissue defects were created in n=24 beagles and treated with a bilayer PDCM with high crosslinking (HXL), a bilayer PDCM with low crosslinking (LXL), or a predicate bilayer membrane (Mucograft, MG). Untreated defects served as controls. Animals were euthanized at 4, 8, and 12 weeks. Qualitative and semiquantitative analyses assessed membrane presence, inflammation, and subepithelial healing, while membrane thickness was quantified across timepoints. All membranes supported successful healing with decreasing inflammation over time. At 4 weeks, MG demonstrated greater membrane thickness (p = 0.023) and inflammation (p = 0.004) than LXL. At 8 weeks, both HXL and LXL showed reduced membrane presence relative to MG (p = 0.001), and this difference persisted at 12 weeks (p = 0.018). At 12 weeks, LXL achieved superior subepithelial healing compared with MG (p = 0.047), with more organized collagen and improved integration. Overall, LXL provided a favorable balance of stability, integration, and biocompatibility, supporting coordinated soft tissue remodeling.
PMID: 41940885
ISSN: 1536-3732
CID: 6025082

3D printing as an innovative tool in personalized management of complex airway diseases: a literature review

Munkwitz, Sara E; Todd, Emily A; Wu, Shangtao; Gangadharan, Sidhu; Majid, Adnan; Iglesias, Nicholas J; Nayak, Vasudev Vivekanand; Witek, Lukasz; Coelho, Paulo G; Buitrago, Daniel H
BACKGROUND AND OBJECTIVE/UNASSIGNED:Personalized medicine tailors interventions to a patient's unique anatomy and physiology. Three-dimensional printing (3DP) enables this precision for complex airway disease, including tracheal stenosis, tracheobronchomalacia, aerodigestive fistulas, and segmental defects, where conventional silicone or metallic stents and surgical reconstruction often fail to provide durable, anatomically congruent solutions. Tissue engineering and 3DP promise patient-specific devices and regenerative scaffolds that maintain patency, resist collapse, and minimize immunogenicity. This review synthesizes clinical and preclinical progress, highlighting materials, design strategies, biologic integration, and translational barriers. METHODS/UNASSIGNED:implantation. Pediatric (<18 years), egg/mouse/rat preclinical studies, review articles, and abstracts were excluded. Data extracted included publication details, participant characteristics, device materials and printing methods, and outcomes. KEY CONTENT AND FINDINGS/UNASSIGNED:From 808 records, 16 clinical and 56 preclinical studies were analyzed. Clinically, indirect 3DP with silicone or metallic alloys predominated, creating Y-stents or straight stents for post-lung transplant (LTx) stenosis, tracheobronchomalacia, granulomatosis with polyangiitis, malignant obstruction, and aerodigestive fistulas. 3DP technologies facilitate the synthesis of customized stents that can better conform to individual airway geometries, offering more precise therapeutic options than conventional one-size-fits-all devices. In parallel, preclinical studies aim to address the limitations observed within clinical settings by focusing on long-term, regenerative solutions. Preclinical studies focused on biodegradable scaffolds, commonly polycaprolactone (PCL), enhanced through surface modification or hybridization with hydrogels such as gelatin methacryloyl (GelMA) or silk fibroin and bioactive factors like transforming growth factor-β (TGF-β) or stromal cell-derived factor-1 (SDF-1). Bilayer constructs with epithelial and chondrogenic components supported epithelialization, cartilage formation, and vascularization. Advanced strategies such as exosome use, ferroptosis inhibition, and heterotopic preconditioning improved integration. CONCLUSIONS/UNASSIGNED:3DP enables anatomically tailored airway implants and promising regenerative scaffolds. Translation is limited by technical variability, regulatory complexity, and sparse long-term data. Standardized protocols, rigorous trials, and multidisciplinary collaboration are essential to bring 3DP airway reconstruction into clinical practice.
PMCID:13077396
PMID: 41988307
ISSN: 2072-1439
CID: 6028032

3D Printed Beta-TCP Ceramic Bone Replacement Manufactured by Lithography-Based Ceramic Manufacturing: A Short-Term Pilot Study

Diaz, Allison L; Torroni, Andrea; Flores, Jackson L; Tovar, Nick; Bergamo, Edmara T P; Graciliano Silva, Bruno Luis; Witek, Lukasz
Clinical application of beta-tricalcium phosphate (β-TCP) has been limited by a lack of bone infiltration within its bulk form. Lithography-based ceramic manufacturing (LCM), a novel additive manufacturing (AM) technique, leverages photopolymerization to create β-TCP structures with higher feature resolution and surface quality than traditional techniques. This modality allows for a more efficient and precise means to control implant microarchitecture and macroarchitecture, enabling the production of novel implant configurations. This pilot study explores the bone regenerative capacity of lithography-based ceramic-manufactured 100% β-TCP scaffolds for the repair of critically sized mandibular defects in a skeletally mature rabbit model. Quantitative and qualitative analyses of regenerated bone were performed using micro-computer tomography (micro-CT) and two-dimensional histologic analysis, respectively. Three-dimensional volumetric reconstruction revealed bridging bone in sites treated with β-TCP implants, yielding ~8.6±3.5% of regenerated bone within the construct and ~33±3.2% remaining scaffold volume. Bone regeneration and remaining scaffold quantification were corroborated using traditional two-dimensional histologic micrographs and three-dimensional volumetric analysis (P<0.05). Qualitative histologic analysis revealed vascularized woven and lamellar bone, with no evidence of ectopic bone, excess inflammation, or fracture. Bone regeneration in this short-term rabbit model following a critical-sized mandibular defect repaired with LCM β-TCP scaffolds demonstrated analogous radiographic and histologic properties to native bone.
PMID: 41182809
ISSN: 1536-3732
CID: 5959442

Coaxial Bioprinting in Regenerative Medicine: Advances and Emerging Applications

Guanche, Isabella Demirdjian; Joshua, Tina; Munkwitz, Sara E; Torquati, Matteo Simone; Shah, Hana; Tadisina, Kashyap Komarraju; Witek, Lukasz; Nayak, Vasudev Vivekanand; Coelho, Paulo G
Coaxial extrusion-based bioprinting (EBB) is an emerging technology that enables the fabrication of biomimetic tissues with precise structural and biological complexities. This three-dimensional bioprinting technique utilizes specialized concentric nozzles to facilitate the simultaneous extrusion of distinct biomaterials, enabling the fabrication of layered constructs that closely resemble native tissues. Unlike traditional extrusion-based methods, coaxial printing allows for independent control over core and shell materials. This enables multimaterial integration, and tailored microenvironments that conventional extrusion methods cannot achieve. Recent technical innovations in coaxial EBB also include improved nozzle designs and bioink formulations, which have contributed to enhanced functional mimicry of native tissues and mechanical integrity of printed constructs. Coaxial EBB has demonstrated potential in spinal cord injury repair, perfusable small-diameter vessel engineering, accurate tumor microenvironment replication for oncology research, and complex organoid systems for personalized medicine. Despite these advancements, persistent challenges in coaxial EBB include maintaining cell viability under shear stress, optimizing bioink rheology, preventing nozzle clogging, and managing regulatory considerations. Future research directions involve the development of predictive computational models and the incorporation of innovative biomaterials for dynamic functionality. Addressing these challenges would allow the full therapeutic and clinical potential of coaxial bioprinting in regenerative medicine to be achieved. This review discusses and summarizes these advancements and limitations in coaxial EBB over the last decade, with an emphasis on applications in regenerative medicine.
PMID: 41027418
ISSN: 1937-3376
CID: 6041622

Comparative Osseointegration in Different Parts of Bone: A Systematic Review of in vivo Experiments

Albuquerque, Gustavo M; Telles, Paula Maria G S; Maluf, Caroline Vieira; Castellon, Maria; Suarez, Camila; Sandino, Adriana I; Bonfante, Estevam A; Witek, Lukasz; Nayak, Vasudev Vivekanand; Coelho, Paulo G
Osseointegration is critical for the long-term success of endosteal implants, as it is influenced by factors such as implant design, material selection, and site of implantation. Considering the structural and vascular properties of trabecular bone, it is reasonable to hypothesize that osseointegration could be enhanced in this region. However, emerging evidence indicates that cortical bone frequently offers a more favorable environment for osseointegration. The objective was to conduct a systematic review of preclinical translational studies comparing osseointegration outcomes around implants placed in cortical and trabecular bone. Preclinical studies comparing bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) between cortical and trabecular regions in animals with solid endosteal implants were retrieved from the PubMed, EMBASE, and Cochrane databases. We included randomized and nonrandomized preclinical translational trials published in English between 2014 and 2024 that reported at least one outcome of interest. Exclusion criteria comprised in vitro or ex vivo experiments, research involving human subjects, studies using powder, liquid, or plasma implants, abstracts, technical descriptions, and narrative or systematic reviews. The systematic review comprised 15 studies, which included a total of 298 animals and 877 implants. The mean follow-up period ranged between 4 and 17 weeks. In 13 studies, the cortical bone region demonstrated higher BIC values, with differences in BIC between cortical and trabecular bone ranging from 5.55% to 49.55% during the first 4 weeks, 1.80% to 51.30% between 4 and 8 weeks, and 9.65% to 35.41% following the 8-week healing period. Regarding BAFO values, data were reported in three studies, all of which indicated elevated values in cortical bone. The mean difference in the first 4 weeks ranged from 15.83% to 29.92%, and from 26.33% to 60.11% after 4 weeks of healing. These findings suggest that cortical regions exhibit enhanced short- and long-term osseointegration outcomes compared to trabecular bone regions. Impact Statement The specific site of implantation significantly influences the degree and rate of osseointegration. Trabecular bone, characterized by its high porosity and larger surface area relative to volume, facilitates the diffusion of nutrients and oxygen from the surrounding marrow and blood vessels. Nevertheless, emerging evidence indicates that cortical bone, due to its greater density and superior mechanical properties, often provides a more stable environment for osseointegration compared to trabecular bone. This systematic review of preclinical studies represents the first comprehensive effort to evaluate and compare osseointegration in cortical versus trabecular bone.
PMID: 41051945
ISSN: 1937-3376
CID: 5951542