Faculty Bibliography

This manuscript reviews the transformative impact of 3-dimensional (3D) printing technologies in the treatment and management of cleft lip and palate (CLP), highlighting its application across presurgical planning, surgical training, implantable scaffolds, and postoperative care. By integrating patient-specific data through computer-aided design and manufacturing, 3D printing offers tailored solutions that improve surgical outcomes, reduce operation times, and enhance patient care. The review synthesizes current research findings, technical advancements, and clinical applications, illustrating the potential of 3D printing to revolutionize CLP treatment. Further, it discusses the future directions of combining 3D printing with other innovative technologies like artificial intelligence, 4D printing, and in situ bioprinting for more comprehensive care strategies. This paper underscores the necessity for multidisciplinary collaboration and further research to overcome existing challenges and fully utilize the capabilities of 3D printing in CLP repair.

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings-for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann^Ⓡ Ti-SLA implants for 21 days. The biofilms included Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus oralis, and Veillonella dispar, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with P. gingivalis, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (p < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (p = 0.038), and cell viability was not affected by LTP (p ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.

The energy state of endosteal implants is dependent on the material, manufacturing technique, cleaning procedure, sterilization method, and surgical manipulation. An implant surface carrying a positive charge renders hydrophilic properties, thereby facilitating the absorption of vital plasma proteins crucial for osteogenic interactions. Techniques to control the surface charge involve processes like oxidation, chemical and topographical adjustments as well as the application of nonthermal plasma (NTP) treatment. NTP at atmospheric pressure and at room temperature can induce chemical and/or physical reactions that enhance wettability through surface energy changes. NTP has thus been used to modify the oxide layer of endosteal implants that interface with adjacent tissue cells and proteins. Results have indicated that if applied prior to implantation, NTP strengthens the interaction with surrounding hard tissue structures during the critical phases of early healing, thereby promoting rapid bone formation. Also, during this time period, NTP has been found to result in enhanced biomechanical fixation. As such, the application of NTP may serve as a practical and reliable method to improve healing outcomes. This review aims to provide an in-depth exploration of the parameters to be considered in the application of NTP on endosteal implants. In addition, the short- and long-term effects of NTP on osseointegration are addressed, as well as recent advances in the utilization of NTP in the treatment of periodontal disease.

Bone tissue regeneration is a rapidly evolving field aimed at the development of biocompatible materials and devices, such as scaffolds, to treat diseased and damaged osseous tissue. Functional scaffolds maintain structural integrity and provide mechanical support at the defect site during the healing process, while simultaneously enabling or improving regeneration through amplified cellular cues between the scaffold and native tissues. Ample research on functionalization has been conducted to improve scaffold-host tissue interaction, including fabrication techniques, biomaterial selection, scaffold surface modifications, integration of bioactive molecular additives, and post-processing modifications. Each of these methods plays a crucial role in enabling scaffolds to not only support but actively participate in the healing and regeneration process in bone and joint surgery. This review provides a state-of-the-art, comprehensive overview of the functionalization of scaffold-based strategies used in tissue engineering, specifically for bone regeneration. Critical issues and obstacles are highlighted, applications and advances are described, and future directions are identified.

Biomimetics is the science of imitating nature's designs and processes to create innovative solutions for various fields, including dentistry and craniofacial reconstruction. In these areas, biomimetics involves drawing inspiration from living organisms/systems to develop new materials, techniques, and devices that closely resemble natural tissue structures and enhance functionality. This field has successfully demonstrated its potential to revolutionize craniofacial procedures, significantly improving patient outcomes. In dentistry, biomimetics offers exciting possibilities for the advancement of new dental materials, restorative techniques, and regenerative potential. By analyzing the structure/composition of natural teeth and the surrounding tissues, researchers have developed restorative materials that mimic the properties of teeth, as well as regenerative techniques that might assist in repairing enamel, dentin, pulp, cementum, periodontal ligament, and bone. In craniofacial reconstruction, biomimetics plays a vital role in developing innovative solutions for facial trauma, congenital defects, and various conditions affecting the maxillofacial region. By studying the intricate composition and mechanical properties of the skull and facial bones, clinicians and engineers have been able to replicate natural structures leveraging computer-aided design and manufacturing (CAD/CAM) and 3D printing. This has allowed for the creation of patient-specific scaffolds, implants, and prostheses that accurately fit a patient's anatomy. This review highlights the current evidence on the application of biomimetics in the fields of dentistry and craniofacial reconstruction.

Osseodensification enhances the stability of endosteal implants. However, pre-clinical studies utilizing osseodensification instrumentation do not account for the limited presence of trabeculae seen clinically. This study aimed to evaluate the effect of osseodensification instrumentation on osteotomy healing in scenarios with and without the presence of trabecular bone. A ~10 cm incision was made over the hip of twelve sheep. Trabecular bone was surgically removed from twelve sites (one site/animal; negative control (Neg. Ctrl)) and left intact at twelve sites (one site/animal; experimental group (Exp.)). All osteotomies were created using the osseodensification drilling protocol. Each osteotomy received an endosteal implant and was evaluated after 3 or 12 weeks of healing (n = 6 animals/time). Histology revealed increased woven and lamellar bone surrounding the implants in the Exp. group relative to the Neg. Ctrl group. The Exp. group demonstrated the presence of bone fragments, which acted as nucleating sites, thereby enhancing the bone formation and remodeling processes. Bone-to-implant contact (%BIC) and bone area fractional occupancy (%BAFO) were significantly higher in the Exp. group relative to the Neg. Ctrl group both at 3 weeks (p = 0.009 and p = 0.043) and 12 weeks (p = 0.010 and p = 0.008). Osseodensification instrumentation in the presence of trabecular bone significantly improved osseointegration. However, no negative influences such as necrosis, inflammation, microfractures, or dehiscence were observed in the absence/limited presence of trabeculae.

Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption.