Faculty Bibliography

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.

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.

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.

Tricalcium phosphate (TCP) bioceramics, available as α- and β-polymorphs, are frequently employed in the production of three-dimensionally (3D) printed bone scaffolds. Although hydrothermal immersion processing (HP) and sintering (S) are commonly adopted as post-printing techniques for bioceramics, a comprehensive comparative analysis of their effects on the osteogenic performance of α- and β-polymorphs in vivo remains inadequately investigated. In this study, α-TCP and β-TCP scaffolds were fabricated via direct ink writing and subjected to hydrothermal immersion processing (α-TCP/HP) and sintering (β-TCP/S) prior to implantation in n = 12 skeletally mature sheep (n = 1 scaffold per group per animal), and the outcome variables were evaluated at 3 and 12 weeks postoperatively (n = 6 sheep per time point). The quantitative results showed no significant differences in bone deposition or scaffold resorption at 3 weeks postoperatively (p = 0.618 and p = 0.898, respectively). However, at 12 weeks, there was a significant increase in osteogenesis and scaffold resorption in the β-TCP/S cohort relative to the α-TCP/HP counterparts (p < 0.001 and p = 0.004, respectively). β-TCP scaffolds subjected to post-print sintering exhibited superior osteoconductive and resorptive profiles compared to hydrothermal immersion-processed α-TCP scaffolds over the 12-week healing period.

Trabecular Metal^TM (TM) dental implants comprise a tantalum (Ta)-based biomimetic open-cell structure designed to replicate the structural, functional, and physiological properties of cancellous bone. Yet, the current literature primarily focuses on the evaluation of osseointegration outcomes surrounding TM implants in uncompromised bone environments and/or brief periods of observation in pre-clinical models. In addition, the performance of TM implants in bony defect environments reconstructed with allogenic grafts and bioactive molecules, such as platelet-rich fibrin (PRF), has not been thoroughly investigated. This longitudinal, randomized clinical trial comprised patients presenting with completely edentulous maxillaries. Guided Bone Regeneration (GBR) was performed using a cortico-cancellous allograft/PRF agglomerate. After 26 weeks, bone biopsies were obtained, followed by the insertion of a TM implant, after which patients were allowed to heal for 52 weeks for assessment of osseointegration. Qualitatively, histomicrographs at 26 weeks confirmed the presence of newly formed bone extending from the periphery of defects and along the direct surface of the allograft. TM implant biopsies at 52 weeks demonstrated osseointegration with bone ongrowth and ingrowth at the interconnected, porous trabecular region. These histological characteristics were consistent across all patients. No metal debris was detected, and the TM implants maintained their porous structure throughout the study period. TM implants placed in PRF-augmented allograft-reconstructed maxillae fostered a conducive environment for osseointegration. By leveraging the open-cell Ta structure, robust new bone formation was achieved without signs of adverse tissue reactions.

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.