Fabiana Aellos

All Publications

• 5-FU Weakens Defensive Functions of the Junctional Epithelium. Journal of periodontal research Aellos, F., Ramos, A., Civit-Balta, A., Grauer, J. A., Cuevas, P. L., Rao, S., Yuan, X., Liu, B., Helms, J. A. 2025

  Abstract

  To investigate additional factors contributing to the pathophysiology of chemotherapy-induced oral mucositis and periodontitis beyond the systemic immune suppression caused by the chemotherapeutic agent 5-Fluorouracil (5-FU).5-Fluorouracil was topically delivered to the non-keratinized, rapidly proliferating junctional epithelium (JE) surrounding the dentition, and acts as an immunologic and functional barrier to bacterial ingression. Various techniques, including EdU incorporation, quantitative immunohistochemistry (qIHC), histology, enzymatic activity assays, and micro-computed tomographic (μCT) imaging, were employed to analyze the JE at multiple time points following topical 5-FU treatment. Systemic 5-FU delivery was used for comparison, and all 5-FU treated tissues were compared to vehicle-treated controls.We first showed that systemic 5-FU blocked mitotic activity that rapidly led to JE atrophy. This atrophy was accompanied by suppression of the immune system. We then demonstrated that topical 5-FU delivery effectively inhibited cell proliferation in the JE. Quantitative immunohistochemical (qIHC) analyses further demonstrated a progressive breakdown in JE barrier functions following topical 5-FU. CBC analyses confirmed that topical 5-FU did not alter the innate immune system but did suppress the local immune response of the JE. The longer-term consequences of this disruption in JE barrier functions were significant alveolar bone loss and an increase in porosity. Together, these results document the essential requirement for rapid JE cell proliferation to maintain homeostasis of the periodontium.The reduction of cell division in the JE due to 5-FU treatment directly compromises both its structural integrity and immune surveillance capabilities, contributing to the destruction of periodontal hard tissues.

  View details for DOI 10.1111/jre.13375

  View details for PubMedID 39799458

• Non-invasive and quantitative methods for assessment of blood flow in periodontal and oral soft tissues: a systematic review. Frontiers in dental medicine Rodriguez, A., Kripfgans, O., Aellos, F., Velasquez, D., Baltazar, A., Chan, H. 2025; 6: 1587821

  Abstract

  Objectives: Understanding the available methods to study blood flow in the oral cavity can enhance knowledge of research methodology on periodontal circulation related to disease initiation and progression as well as wound healing. This study aims to systematically review non-invasive techniques that allow for the assessment of oral tissue perfusion in clinical and pre-clinical studies.Methods: A complete electronic literature search in 5 databases (NLM PubMed, Embase, EBSCOhost CINAHL, EBSCOhost Dentistry and Oral Sciences Source, and Wiley Cochrane Central Register of Controlled Trials) was conducted by two reviewers. The search terms included gingival blood flow, tissue perfusion, imaging perfusion, soft tissue perfusion, diagnostic, vascularization, soft tissue, and microvascularization. The focused question is: What are the available non-invasive and quantitative imaging techniques used to evaluate oral and periodontal tissue perfusion?Results: A total of 79 articles were included for qualitative analysis. Various methods were identified, including Laser Doppler Flowmetry (LDF), Laser Speckle Contrast Imaging (LSCI), Spectral Imaging Methods (such as Diffuse Reflectance Spectroscopy), Ultrasound (US), Intravital Video Microscopy, and Oral Videocapillaroscopy. LDF is the most applied to estimate blood flow in a small focal area for the study of periodontal diseases and oral wound healing, among other indications. LSCI, providing surrogate superficial blood flow values in a 2-dimensional, larger field-of-view, has been used for similar reasons. The use of cross-sectional ultrasound is on a rise to record blood velocity and blood volume using color flow and color power modes, respectively. Comparisons of the available technologies revealed their strengths and limitations related to their spatial resolution, sensitivity, reliability, accuracy, invasiveness, dependence of (image) data in the field of view relative to probe positioning and angulation, and safety. The ideal features of such a device pertinent to probe geometry, data acquisition, recording, and infection control needs were also discussed.Conclusions: A few imaging technologies have been identified in the literature to study blood flow in the oral cavity. These methods could potentially augment our ability to diagnose oral diseases and monitor wound healing objectively and timely. In combination, these could potentially enhance treatment outcomes significantly.

  View details for DOI 10.3389/fdmed.2025.1587821

  View details for PubMedID 40475388

• Evaluation of Postoperative Outcomes Following Early and Late Palate Repair: A Preclinical Study. The Journal of craniofacial surgery Aellos, F., Verma, I., Ly, M., Hoy, M., Quach, T., Rosbander, I., Sandoval, A., Wolvis, E., Turkkahraman, H., Helms, J. A. 2024

  Abstract

  To quantitatively assess the impact of early versus late surgical intervention on midfacial growth using a mouse model.A full-thickness mucoperiosteal flap surgery was performed on newborn (P17) mice and on neonatal (P30) mice. High-resolution micro-computed tomographic imaging coupled with histomorphometric analyses was used to assess craniomaxillofacial growth. Histology and immunohistochemical analyses were used to assess cellular and molecular responses postsurgery.Early surgical intervention at P17 resulted in significant midfacial growth arrest, with pronounced maxillary hypoplasia. Histomorphometric analyses revealed significant (P < 0.05) growth disruptions in the mid-palatal suture complex, including premature removal of the cartilaginous growth plate and its replacement by bone. In the suture itself, cell proliferation was significantly reduced (P < 0.05) compared with controls. The same surgical intervention performed in mice at P30 did not lead to significant midfacial growth arrest.Early surgical intervention in a mouse model mirrors the adverse growth outcomes in children undergoing early cleft repair. Molecular and cellular observations accompanying this midfacial growth arrest may inform therapeutic strategies to mitigate midfacial growth disturbances in patients and highlight the need for refined surgical techniques to minimize adverse growth outcomes.

  View details for DOI 10.1097/SCS.0000000000010827

  View details for PubMedID 39499137

• Dynamic analyses of a soft tissue-implant interface: Biological responses to immediate versus delayed dental implants. Journal of clinical periodontology Aellos, F., Grauer, J. A., Harder, K. G., Dworan, J. S., Fabbri, G., Cuevas, P. L., Yuan, X., Liu, B., Brunski, J. B., Helms, J. A. 2024

  Abstract

  To qualitatively and quantitatively evaluate the formation and maturation of peri-implant soft tissues around 'immediate' and 'delayed' implants.Miniaturized titanium implants were placed in either maxillary first molar (mxM1) fresh extraction sockets or healed mxM1 sites in mice. Peri-implant soft tissues were evaluated at multiple timepoints to assess the molecular mechanisms of attachment and the efficacy of the soft tissue as a barrier. A healthy junctional epithelium (JE) served as positive control.No differences were observed in the rate of soft-tissue integration of immediate versus delayed implants; however, overall, mucosal integration took at least twice as long as osseointegration in this model. Qualitative assessment of Vimentin expression over the time course of soft-tissue integration indicated an initially disorganized peri-implant connective tissue envelope that gradually matured with time. Quantitative analyses showed significantly less total collagen in peri-implant connective tissues compared to connective tissue around teeth around implants. Quantitative analyses also showed a gradual increase in expression of hemidesmosomal attachment proteins in the peri-implant epithelium (PIE), which was accompanied by a significant inflammatory marker reduction.Within the timeframe examined, quantitative analyses showed that connective tissue maturation never reached that observed around teeth. Hemidesmosomal attachment protein expression levels were also significantly reduced compared to those in an intact JE, although quantitative analyses indicated that macrophage density in the peri-implant environment was reduced over time, suggesting an improvement in PIE barrier functions. Perhaps most unexpectedly, maturation of the peri-implant soft tissues was a significantly slower process than osseointegration.

  View details for DOI 10.1111/jcpe.13980

  View details for PubMedID 38708491

• Linking the Mechanics of Chewing to Biology of the Junctional Epithelium. Journal of dental research Yuan, X., Liu, B., Cuevas, P., Brunski, J., Aellos, F., Petersen, J., Koehne, T., Bröer, S., Grüber, R., LeBlanc, A., Zhang, X., Xu, Q., Helms, J. A. 2023: 220345231185288

  Abstract

  The capacity of a tissue to continuously alter its phenotype lies at the heart of how an animal is able to quickly adapt to changes in environmental stimuli. Within tissues, differentiated cells are rigid and play a limited role in adapting to new environments; however, differentiated cells are replenished by stem cells that are defined by their phenotypic plasticity. Here we demonstrate that a Wnt-responsive stem cell niche in the junctional epithelium is responsible for the capability of this tissue to quickly adapt to changes in the physical consistency of a diet. Mechanical input from chewing is required to both establish and maintain this niche. Since the junctional epithelium directly attaches to the tooth surface via hemidesmosomes, a soft diet requires minimal mastication, and consequently, lower distortional strains are produced in the tissue. This reduced strain state is accompanied by reduced mitotic activity in both stem cells and their progeny, leading to tissue atrophy. The atrophied junctional epithelium exhibits suboptimal barrier functions, allowing the ingression of bacteria into the underlying connective tissues, which in turn trigger inflammation and mild alveolar bone loss. These data link the mechanics of chewing to the biology of tooth-supporting tissues, revealing how a stem cell niche is responsible for the remarkable adaptability of the junctional epithelium to different diets.

  View details for DOI 10.1177/00220345231185288

  View details for PubMedID 37555395

• Clinical and cone beam computed tomography outcomes of maxillary anterior implant restorations after immediate implant placement with interim restorations: A 1- to 14-year retrospective analysis. The Journal of prosthetic dentistry Bernal, G., Ruiz, L., Aellos, F., Salazar, C., Sadowsky, S. J. 2023

  Abstract

  STATEMENT OFPROBLEM: Achieving and maintaining optimal tissue health and esthetics when immediately placing maxillary anterior implants with interim restorations has been challenging and the clinical outcomesheterogenous.PURPOSE: The purpose of this retrospective study was to evaluate the clinical outcomes of immediate placement of maxillary anterior implants with interim restorations and compare the tomographic and clinical results before and after implant placement in participants followed for 1 to14 years.MATERIAL AND METHODS: Twenty participants receiving 25 postextraction single implants in the anterior maxilla were studied. Clinical parameters included pink esthetic score (PES) and white esthetic score (WES), peri-implant phenotype, implant probing, plaque index, and cone beam computed tomography (CBCT) to compare initial and at least 1 year after crown placement (postoperative). For qualitative variables, a descriptive analysis was carried out. The PES and WES results were analyzed by using nonparametric statistics, the median (ME) and the interquartile range (IQR) were used as summary measures, and the Wilcoxon sum of signs test was used to compare the total scores between the intervention area and the contralateral tooth. To compare pre- and postoperative data points, the paired t test was used (alpha=.05).RESULTS: Mean±standard deviation (SD) time of follow-up was 7.6±4.2 years. Twenty participants with a mean±SD age of 62.4±11.0 years old received 25 implants. Mean±SD initial torque value at implant placement was 38.6±9.63Ncm. Bone height at the top of the alveolar ridge (BH) and bone width at the middle of the alveolar ridge (BW2) showed a statistically significant decrease between the initial and subsequent CBCT measurements (both P<.001). Likewise, the bone width at the alveolar crest (BW1) showed a statistically significant decrease between the initial and post-CBCT measurements (P=.006). Facial bone integrity (FBI) revealed a statistically significant increase between the initial and postoperative time periods (P<.001). The PES index showed a median of 9.0 IQR (8-10), statistically lower than the contralateral tooth (P=.032). No significant differences were found for the WES index or for FBI, regardless of the peri-implant phenotype.CONCLUSIONS: Immediate implant placement in the maxillary anterior sextant was found to be a predictable procedure with good esthetic results when the protocol described was used. Labial bone loss is inevitable after tooth extraction but can be compensated for by filling the space with a xenograft material. Long-term gingival tissue integrity was maintained, regardless of phenotype, in periodontally healthy participants.

  View details for DOI 10.1016/j.prosdent.2023.05.028

  View details for PubMedID 37451900

• Wnt/beta-Catenin Signaling in Craniomaxillofacial Osteocytes. Current osteoporosis reports Cuevas, P. L., Aellos, F., Dawid, I. M., Helms, J. A. 2023

  Abstract

  PURPOSE OF REVIEW: There is a growing appreciation within the scientific community that cells exhibit regional variation. Whether the variation is attributable to differences in embryonic origin or anatomical location and mechanical loading has not been elucidated; what is clear, however, is that adult cells carry positional information that ultimately affects their functions. The purpose of this review is to highlight the functions of osteocytes in the craniomaxillofacial (CMF) skeleton as opposed to elsewhere in the body, and in doing so gain mechanistic insights into genetic conditions and chemically-induced diseases that particularly affect this region of our anatomy.RECENT FINDINGS: In the CMF skeleton, elevated Wnt/beta-catenin signaling affects not only bone mass and volume, but also mineralization of the canalicular network and osteocyte lacunae. Aberrant elevation in the Wnt/beta-catenin pathway can also produce micropetrosis and osteonecrosis of CMF bone, presumably due to a disruption in the signaling network that connects osteocytes to one another, and to osteoblasts on the bone surface.

  View details for DOI 10.1007/s11914-023-00775-w

  View details for PubMedID 36807035