Faculty Bibliography

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.

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.

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.

Two-photon polymerization (2PP) has enabled three-dimensional printing at micro- and nanometer level resolution, allowing for the fabrication of patient-specific implants and finely structured cell scaffolds. This comprehensive review highlights recent advancements in integrating 2PP across various medical specialties, emphasizing its potential role in clinical and translational settings including ophthalmology, orthopedics, neurology, dermatology, and otolaryngology. Despite technological achievements, significant challenges hinder its widespread use, which are also discussed. This includes scaling of manufacturing processes, ensuring long-term biocompatibility of fabricated structures, and a lack of 2PP research in other medical fields. Advancements in biomaterials, photoinitiators, and integrated fabrication approaches within 2PP could significantly impact clinical practice and further improve patient outcomes.

OBJECTIVE/UNASSIGNED:Reconstruction of critical-sized bone defects, particularly in the cranio-maxillofacial region, presents unique challenges due to the need for integration with adjacent well-vascularized tissue and the absence of significant load-bearing requirements. This study evaluated the clinical readiness of bone tissue engineering (BTE) for critically sized cranial defects using custom 3D-printed hydroxyapatite scaffolds augmented with either recombinant human bone morphogenetic protein-2 (rhBMP-2) or dipyridamole (DIPY) in a highly translational nonhuman primate model. METHODS/UNASSIGNED: = 3). Bone growth and integration were assessed over 12 months through serial CT scans, followed by ex vivo micro-CT scanning, histology, and nanoindentation testing. RESULTS/UNASSIGNED:< 0.05). CONCLUSIONS/UNASSIGNED:Reconstructing critically sized cranial defects with custom 3D-printed hydroxyapatite scaffolds was successful and yielded favorable results in this model. Scaffolds augmented with rhBMP-2 demonstrated superior bone ingrowth, integration, and mechanical properties, highlighting their potential as a viable alternative to autografts and allograft materials for cranioplasty.

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.

Exosomes, nanoscale extracellular vesicles, have garnered substantial interest in biomedical research owing to their critical roles in intercellular communication, diagnostics, and regenerative therapeutics. Among biomolecules investigated in regenerative medicine, exosomes are one of the most intensively researched. While no clinical trials have yet been conducted to assess their regenerative efficacy in human dental applications, a rapidly growing body of preclinical research highlights their therapeutic potential in oral and maxillofacial regeneration. Dental tissue-derived exosomes, most notably from dental pulp stem cells, periodontal ligament stem cells, gingival fibroblasts, and stem cells from exfoliated deciduous teeth, have shown the ability to promote regeneration of bone, the periodontal ligament and other supporting tissues. Moreover, these exosomes have demonstrated potential roles in modulating orthodontic tooth movement and alleviating temporomandibular joint disorders. Preclinical studies included in this review consistently reported improved bone regeneration outcomes, such as increased bone volume, mineralization, and osteogenic marker expression following exosome application. Importantly, exosomes have also exhibited potent immunomodulatory effects, notably through inhibition of inflammation in bone defects and periodontitis models. The therapeutic versatility of exosomes is further reflected in their application across several fields of dentistry, such as periodontitis therapy, pulp regeneration, alveolar bone regeneration, and immune regulation. The majority of the studies highlighted the anti-inflammatory, pro-angiogenic, and osteoinductive features of exosomes, derived from diverse cellular sources. These promising preclinical outcomes collectively indicate that exosome-based therapies hold strong potential for translation into clinical dental practice, offering a novel, cell-free, and biologically targeted strategy to craniofacial tissue regeneration.

OBJECTIVES/OBJECTIVE:This study aims to explore the application of Fused Deposition Modeling (FDM) as a 3D printing technique for developing endosseous Polyetheretherketone (PEEK) dental implants. Specifically, the primary aim of the study is to systematically investigate the effects of key FDM processing parameters, including thermal conditions, print speed, layer height, build orientation, and post-processing heat treatments, on the mechanical and thermal properties of PEEK implants. By conducting an in-depth analysis, this study aims to establish optimized processing guidelines for the reliable manufacturing of high-performance, clinically viable PEEK dental implants. METHODS:PEEK dental implants were fabricated using FDM with variations in thermal conditions (nozzle, bedplate, and chamber temperatures), print speed, layer height, build orientation, and post-print heat treatments. Mechanical testing (compression and fatigue), detailed thermal characterization using Differential Scanning Calorimetry (DSC), and fractographic analysis were performed. Finite Element Analysis (FEA) was also conducted to understand the implant's load-bearing performance. RESULTS:Nozzle temperature dictates implant resolution, while chamber temperature is a key determinant of implant crystallinity. Interestingly, for PEEK dental implants, all the FDM thermal processing conditions play a crucial role in influencing the part's thermal properties. Moreover, print speed plays an essential role in developing dimensionally accurate high-strength implants. Notably, the fractographic analysis of the failed implants revealed interesting multimodal fracture behavior specific to 3D-printed threaded implants. FEA demonstrates that the implants tend to buckle under load and break at the implant-abutment interface, consistent with experimental results. Furthermore, fatigue testing reveals that PEEK implants, fabricated at a specific build orientation with respect to the bedplate, suffice the Food and Drug Administration durability requirements. SIGNIFICANCE/CONCLUSIONS:These findings underscore the clinical potential of FDM-developed PEEK as a customizable, lightweight, and durable alternative to conventional metallic implants, paving the way for next-generation patient-specific lightweight dental implant solutions.

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.

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.