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Postmortem Analysis of Osseointegration in Cementless Acetabular Components After Total Hip Arthroplasty: A Multimodal Study
Saba, Braden V; Schaffler, Benjamin; Martins de Souza, Bruno; Schaffer, Olivia; Fallah, Cameron; Alhaddad, Noor; Montague, Michael; Fritz, Jan; Hopper, Robert; Engh, Charles A; Witek, Lukasz; Schwarzkopf, Ran
INTRODUCTION/BACKGROUND:Press-fit acetabular components achieve long-term fixation through osseointegration, yet the extent of bone ingrowth necessary for durable stability in well-functioning implants remains unclear. Postmortem retrievals provide a unique opportunity to directly assess the bone-cup interface in clinically successful total hip arthroplasties (THAs). This study evaluated osseointegration and biomechanical fixation strength in deceased-donor acetabular components to better define the characteristics of stable long-term fixation. METHODS:Cadaver pelvis specimens containing uncemented THAs from a single institution were evaluated. There were 29 acetabular components that underwent axial pull-out testing using a universal testing machine. A total of seven of these were additionally processed for histologic evaluation, including dehydration, acrylic embedding, thin-sectioning, staining, and digital imaging. Osseointegration was quantified by bone-area fraction occupancy (%BAFO), representing the proportion of bone occupying the porous thread spaces of the cup. RESULTS:All 29 specimens failed through fracture of the ilium rather than at the bone-cup interface, indicating that the mechanical integrity of the osseointegrated construct exceeded that of the surrounding bone under axial tension. Among the seven histologically analyzed components, %BAFO ranged from 4.2 to 27.0% (mean 15.1%), despite all implants being clinically stable at the time of death. There were no significant linear correlations observed between %BAFO and time implanted, fracture load, or body mass index. A significant quadratic relationship between %BAFO and age was identified, peaking near 81 years. CONCLUSIONS:Cementless acetabular components exhibited strong fixation despite modest osseointegration, with failure occurring through host bone on axial testing. Durable biological fixation appears achievable with limited, but mechanically favorable bone ingrowth.
PMID: 42069020
ISSN: 1532-8406
CID: 6029862
Extended hydrothermal aging and glass infiltration on minimally processed recycled 3Y-TZP: microstructural and optical properties
Strazzi-Sahyon, Henrico B; Silva, Bruna M; Campos, Tiago M B; Dos Santos, Claudinei; Piza, Mariana M T; Bergamo, Edmara T P; Tebcherani, Sergio M; Witek, Lukasz; Coelho, Paulo G; Yamaguchi, Satoshi; Bonfante, Estevam A
This study evaluated the effects of glass infiltration and hydrothermal aging on the microstructural and optical properties of minimally processed recycled 3Y-TZP. Unprocessed 3Y-TZP remnants were milled into powder, compacted into discs, and sintered. Specimens were divided into six groups according to glass infiltration and hydrothermal aging (immediate, 50 h, and 100 h at 134 °C/2.2 bar). Particle size was measured by laser diffraction. Density and optical properties (contrast ratio and translucency) were longitudinally evaluated on the same specimens using Archimedes' principle and reflectance measurements (n = 10), whereas crystalline phases (Raman spectroscopy, n = 3), surface and cross-sectional morphology (n = 3), and elemental composition (n = 3) were analyzed on independent specimens allocated to each experimental condition. Color stability and translucency variation were compared with perceptibility (PT = 0.81; TPT = 0.62) and acceptability (AT = 1.77; TAT = 2.62) thresholds (n = 10). Density data were analyzed using one-way repeated-measures ANOVA, while optical properties were analyzed using two-way repeated-measures ANOVA, followed by Tukey's post hoc test. Mean particle size of recycled powder was 1.61 μm. Relative densities for immediate, 50 h, and 100 h groups were 99.68%, 99.24%, and 99.04%. Raman spectra revealed predominance of tetragonal-cubic phases in immediate non-infiltrated group, while monoclinic phase prevailed in others. SEM showed homogeneous surfaces. EDS confirmed zirconium, yttrium, and hafnium in non-infiltrated groups, and silicon, aluminum, sodium, potassium, and calcium in infiltrated. Non-infiltrated groups showed lower contrast ratio and greater translucency than infiltrated, independent of aging. Aging minimally affected optical properties, except infiltrated specimens, where translucency was higher immediately than after 50-100 h. All groups exhibited color and translucency variation below perceptibility and acceptability thresholds. Prolonged hydrothermal degradation influenced the microstructural and optical features of recycled 3Y-TZP, while glass infiltration further modified these characteristics, reducing translucency while increasing opacity and color stability.
PMID: 42624969
ISSN: 1618-1255
CID: 6071568
Dipyridamole-Coated 3D-Printed β-Tricalcium Phosphate Scaffolds: Spectrophotometric Characterization, Drug Release Kinetics, and In Vitro Evaluation to Guide Critical-Sized Bone Defect Repair Studies
Rasane, Purva; Nayak, Vasudev Vivekanand; Weerasinghe Arachchige, Lahiru Chamara; Rice, Eleni; Ashin, Zeinab Fotouhi; Venkatesan, Bharath; Varanasi, Venu; Ono, Noriaki; Young, Simon; Witek, Lukasz
Critical-sized bone defects remain a significant clinical challenge, and dipyridamole (DIPY)-coated 3D-tricalcium phosphate (β-TCP) scaffolds have shown promising osteogenic efficacy in preclinical models. However, the literature on the systematic physicochemical characterization of this scaffold system, including optimization of DIPY loading parameters, release kinetics, and surface properties, is lacking. This study addresses these gaps by characterizing DIPY-loaded 3D-printed β-TCP scaffolds across solid and porous architectures, three coating concentrations (10, 100, and 1000 µM), and three coating volumes (250, 500, and 1000 µL). Under static PBS conditions, drug release over 21 days was quantifiable only at 1000 µM, and release-kinetics modeling (zero-order, Higuchi, and Korsmeyer-Peppas) was therefore restricted to this highest concentration. At 1000 µM, both scaffold types showed biphasic release profiles, with standard empirical models reasonably approximating the overall kinetics, while not fully capturing the biphasic behavior over the entire duration. Porous scaffolds showed significant volume-dependent release (p = 0.002, η
PMCID:13514228
PMID: 42646199
ISSN: 2079-4983
CID: 6071738
Light-based vat-polymerization of electroconductive gelatin methacryloyl composite hydrogels for soft tissue interfacing
Elkhoury, Kamil; Zhou, Jiarui; Usmani, Sadaf; Nagarajan, Vinod; Menon, Abhay; Boitet, Maylis; Hacquebord, Jacques H; Witek, Lukasz; Ramadi, Khalil; Vijayavenkataraman, Sanjairaj
Conductive hydrogels have emerged as promising materials for soft tissue interfacing by combining tissue-like mechanical compliance with electrical conductivity, thereby enabling improved electrical communication with electroactive biological tissues. This work presents an electroconductive composite hydrogel fabricated via light-based vat-polymerization by integrating a choline-based bio-ionic liquid (IL) with gelatin methacryloyl (GelMA). The resulting hydrogels demonstrate tunable conductivity, structural integrity, and high print fidelity when fabricated using digital light processing (DLP) light-based 3D printing. Electrical conductivity was optimized at 20% v/v IL concentration, with the hydrogels demonstrating stable performance for over 28 days. A food-grade photoabsorber was integrated into the formulation to improve DLP resolution and was effectively removed after printing process. The hydrogels supported the human mesenchymal stem cells' viability and proliferation, confirming their cytocompatibility. They also promoted enhanced maturation of primary neurons, demonstrating a supportive microenvironment for neural cells. In vivo implantation of indocyanine green-loaded hydrogels exhibited sustained stability and robust retention of signal over a period of 4 weeks, with histological analysis indicating seamless integration with surrounding tissues. Impedance spectroscopy at both gut and spinal cord interfaces illustrated that GelMA/IL composites achieved the lowest impedance across a range of frequencies, outperforming both GelMA-only and tissue-only conditions. Collectively, these findings position light-based vat-polymerized electroconductive composites as a promising platform for the development of anatomically conformal materials tailored for soft tissue interfacing.
PMID: 42492710
ISSN: 1879-0003
CID: 6071584
Mechanical Constriction of the Maxilla Alters Nasal Architecture
Teixeira, Cristina C; Uribe-Querol, Eileen; Garzón, Daniel L; Sangsuwon, Chinapa; Nervina, Jeanne; Abdullah, Fanar; Alikhani, Mona; Galindo-Solano, Nuria; Serrano-Bello, Janeth; Pérez-Sánchez, Lucia; Witek, Lukasz; Villagómez-Olea, Guillermo; Marichi-Rodríguez, Francisco J; Alikhani, Mani
PMCID:13410686
PMID: 42513341
ISSN: 2077-0383
CID: 6070508
Comparative Histological Evaluation of Collagen Matrix Architectures for Soft Tissue Augmentation in the Oral Cavity: A Preclinical Canine Model
Shah, Hana; Iglesias, Nicholas J; Munkwitz, Sara E; Slavin, Blaire V; Stauber, Zachary M; Ehlen, Quinn T; Nayak, Vasudev Vivekanand; Thaller, Seth R; Witek, Lukasz; Coelho, Paulo G
Intraoral soft-tissue defects are traditionally managed with autogenous connective tissue grafts, though donor site morbidity has driven interest in xenogeneic collagen matrices as alternatives. However, the impact of matrix architecture on soft-tissue integration remains poorly understood. This study compared soft-tissue responses to a sheet-form collagen matrix (ShCM) and a spongy collagen matrix (SpCM) placed beneath full-thickness flaps in a beagle mandibular defect model. Standardized bilateral defects were created in 23 skeletally mature female beagles. Defects were then assigned to serve as the negative control (sham) or were treated with porcine collagen matrix in (i) sheet form (ShCM) (Regenity Biosciences, Oakland, NJ, USA), or (ii) porous/spongy form (SpCM) (Fibro-Gide®, Geistlich Pharma North America, West Windsor Township, NJ, USA). The mandibular sites that received no surgical intervention served as positive controls. Experimental conditions were randomized and interpolated within each animal to minimize anatomical site bias and evaluated histologically at 4- (n = 7), 8- (n = 7), and 12-weeks (n = 9) postoperatively. Histologic sections were evaluated for matrix presence, inflammation, subepithelial healing, and matrix thickness. At 4 weeks, both matrices were present, though SpCM showed significantly higher inflammation scores (p = 0.013). By 8 weeks, ShCM demonstrated greater resorption (p = 0.003) alongside an organized collagen layer with fibroblasts and new microvessels, while SpCM remained thick and porous, with a persistent fibrous capsule and elevated inflammation versus both ShCM (p = 0.002) and sham (p = 0.009). At 12 weeks, inflammation declined and subepithelial healing improved similarly across matrix groups. These findings suggest matrix architecture influences soft-tissue healing outcomes in the oral cavity. Sheet-form matrices may be preferable where biocompatibility and predictable integration are priorities, while spongy matrices may better support long-term space maintenance and tissue ingrowth. However, clinical studies are needed to confirm these translational implications.
PMCID:13295686
PMID: 42351907
ISSN: 2306-5354
CID: 6056252
Rasping in Rhinoplasty: Bone Healing Outcomes With Manual Versus Piezoelectric-Assisted Techniques
Shah, Hana; Munkwitz, Sara E; Iglesias, Nicholas J; Wu, Shangtao; Brochu, Baylee M; Nayak, Vasudev Vivekanand; Jabori, Sinan; Thaller, Seth R; Witek, Lukasz; Coelho, Paulo G
There has been an increasing trend in using piezoelectric devices in craniofacial surgery to selectively cut bone and reduce collateral soft tissue trauma. Although the benefits of piezosurgery have been well demonstrated for osteotomies, its impact on bone healing during rasping remains understudied. This study evaluated bone regeneration following medial maxillary rasping performed with a manual rasp (MR) compared with piezotome-assisted rasping (PR) in a skeletally mature sheep model. Bilateral defects (rasps: ∼2 cm x ∼2 cm) were created along the coronal plane on the anterodorsal aspect of the nasal bone, with PR used on the anatomic right side and MR on the anatomic left side. Nondecalcified histologic processing and analysis was performed on the nasomaxillary bone at 3 and 12 weeks postoperatively (n=6 sheep/timepoint). At 3 weeks, MR-treated defects showed smoother, intact bone defect margins with minimal bone deposition. PR-treated defects displayed more irregular margins with scattered bone fragments, consistent with ultrasonic microfracturing. By 12 weeks, both techniques demonstrated comparable healing patterns with a regenerating nasal bone contour, maturation of bone architecture, visible osteocytes, and no evidence of bone fragments or inflammatory infiltrates. Semiquantitative scoring of osteogenesis revealed statistically homogenous findings between MR and PR usage (p=0.63 at 3 weeks; p=1.00 at 12 weeks). Within the limits of this model, piezotome-assisted rasping altered early bone surface topography but did not impair long-term bone regeneration compared with manual rasping. This provides preclinical support for piezotome use as an alternative bone-modifying technique in rhinoplasty.
PMID: 41557018
ISSN: 1536-3732
CID: 5988262
Histologic Evaluation of Piezotome and Traditional Osteotomy Techniques in Posterior Maxillary Rhinoplasty
Iglesias, Nicholas J; Shah, Hana; Munkwitz, Sara E; Wu, Shangtao; Sheinberg, Derek S; Nayak, Vasudev Vivekanand; Jabori, Sinan K; Thaller, Seth R; Witek, Lukasz; Coelho, Paulo G
Rhinoplasty is the fifth most commonly performed cosmetic surgery globally. While surgical techniques used for rhinoplasty have evolved significantly in the past century, the creation of precise osteotomies remains a cornerstone of the procedure. Recently, piezotomes have been associated with reduced postoperative pain, edema, ecchymosis, complications, and revision rates in rhinoplasty. Despite these clinically significant benefits, there remains a paucity of histologic analysis of osteotomies performed with piezotomes in a large translational preclinical model. In this study, n=12 adult sheep underwent lateral rhinoplasty of the posterior maxilla using each of the three surgical devices: piezotome, manual osteotome, and oscillatory saw. Subjects were randomized to heal for either 3 or 12 weeks postoperatively (n = 6 animals per cohort). En bloc samples were processed and analyzed histologically. A semiquantitative healing scale was used to quantify bony ingrowth into the osteotomy. Wilcoxon signed-rank tests were used to analyze the outcome variable. No statistically significant differences in semiquantitative grades were observed among groups (p > 0.05) at either time point. However, the piezotome was associated with more uniform, reproducible, and smoother osteotomy walls, and smaller bone chips at 3 weeks. At 12 weeks, all osteotomy techniques had complete or near-complete osteogenesis. Use of the piezotome did not completely prevent soft tissue injury. Some osteotomies demonstrated full-thickness penetration and injury to the underlying cartilage. All groups demonstrated comparable healing outcomes after 12 weeks. However, histologic results indicate that reliance solely on device technology may not be sufficient. Clinical judgement of these techniques and relevant case presentations is required to minimize unintended tissue injury.
PMID: 41941121
ISSN: 1536-3732
CID: 6025112
Bone Tissue Engineering Strategies To Treat Critically Sized Defects in Compromised Wound Healing Environments
Munkwitz, Sara E; Shah, Hana; Iglesias, Nicholas J; Camacho, Michelle; Fix, Taylor; Pavon, Cesar; Nayak, Vasudev Vivekanand; Witek, Lukasz; Coelho, Paulo G
Critically sized bone defects are difficult to treat, necessitating tissue engineering strategies to restore form and function. However, translation of these approaches is often constrained by preclinical models that fail to replicate systemic comorbidities commonly seen in clinical practice, such as diabetes, prior irradiation, osteonecrosis, and osteoporosis, and instead favor healthy wound environments that may overestimate efficacy. This comprehensive review aimed to provide a detailed overview of in vivo bone regeneration strategies for critically sized defects specifically within compromised healing environments, summarizing how animal models are developed and how biomaterial, cellular, and drug delivery platforms are tailored to these disease states. Recent work has sought to address key pathological barriers including chronic inflammation, oxidative stress, poor vascularization, hypocellularity, and the limited efficacy of cell-seeding approaches through a range of bioengineered solutions. Strategies include nanoengineered drug delivery systems, bioactive ion-releasing scaffolds, immunomodulatory and antioxidant biomaterials, advanced cell provisioning, and extracellular vesicle-based therapies designed to restore redox balance, promote angiogenesis, and reestablish osteogenesis. Remaining challenges include heterogeneity and poor standardization of defect models, underrepresentation of multimorbidity and treatment-related injury, ethical and logistical barriers to large animal studies, and uncertainty in how best to bridge emerging platforms with regulatory expectations. Future directions will require coordinated refinement of disease-relevant models and development of multifunctional, context-responsive constructs to more reliably predict and improve clinical translation of bone tissue engineering therapies.
PMID: 41937489
ISSN: 2373-9878
CID: 6024952
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