Pulp Survival of Cracked Teeth with Reversible Pulpitis after Orthodontic Banding and Coronal Coverage - A Prospective Cohort Study with One Year Follow Up.

INTRODUCTION: The aim of this prospective study was to investigate the 1-year pulp survival of cracked teeth with reversible pulpitis managed with initial stabilization using orthodontic bands, followed by coronal coverage restorations. METHODS: One-hundred-and-twenty-five patients with a cracked tooth with reversible pulpitis each were recruited. Preoperative patient and tooth data were collected. After definitive pulp diagnoses were determined following an interim period of orthodontic banding, coronal coverage restorations were placed. Cox and logistic regression analyses were used to assess possible prognostic factors and to correlate initial time to pulp stabilization while in orthodontic bands with eventual outcome. Pulp survival was determined using both clinical and radiographic findings. RESULTS: One-hundred-and-six cracked teeth were followed up at 1 year. Pulp survival based on clinical and radiographic findings was found in 81 teeth (76.4%). Out of 25 failures, 11 (44%) required root canal treatment (RCT) in the orthodontic band stage and 10 (40%) required RCT during the process of or after coronal coverage restorations. Four teeth (16%) had incidental findings of periapical radiolucencies at the 1-year review without clinical symptoms. Teeth requiring RCT were found to have required longer periods in orthodontic bands prior to a definitive pulp diagnosis (P < .05). CONCLUSION: A step-by-step approach by using orthodontic banding to monitor pulp status may reduce the incidence of RCT required through definitive coronal coverage restorations for cracked teeth with reversible pulpitis.

Knowledge of undergraduate and postgraduate dental students about managing traumatic dental injuries based on the 2020 International Association of Dental Traumatology guidelines: A online survey of 10 dental schools from 10 countries.

BACKGROUND/AIM: The knowledge of dental students about managing traumatic dental injuries (TDIs) may not be uniform, depending on global location and dental education. The aim of this study was to evaluate the level of knowledge of undergraduate and postgraduate students specializing in endodontics and pediatric dentistry at 10 dental schools in 10 countries about the 2020 International Association of Dental Traumatology (IADT) guidelines regarding the management of TDIs. MATERIALS & METHODS: A previously published questionnaire was used in the current survey. It was an online survey with 12 questions regarding the management of TDIs and some additional questions regarding sociodemographic and professional profiles of the participants were added. The survey was distributed to final-year undergraduate students and postgraduate students in pediatric dentistry and endodontics from 10 dental schools. Simple frequency distributions and descriptive statistics were predominantly used to describe the data. Differences in the median percentage scores among the student categories were assessed using the Kruskal-Wallis test followed by Dwass-Steel-Critchlow-Fligner pairwise comparisons. RESULTS: A total of 347 undergraduates, 126 postgraduates in endodontics, and 72 postgraduates in pediatric dentistry from 10 dental schools participated in this survey. The postgraduates had a significantly higher percentage score for correct responses compared with the undergraduates. No significant difference was observed between the endodontic and pediatric dentistry postgraduates. CONCLUSION: The knowledge possessed by undergraduate and postgraduate students concerning the IADT-recommended management of TDIs varied across the globe and some aspects were found to be deficient. This study emphasizes the critical importance of reassessing the teaching and learning activities pertaining to the management of TDIs.

Generation of Induced Pluripotent Stem Cell-Derived iTenocytes via Combined Scleraxis Overexpression and 2D Uniaxial Tension.

Today's challenges in tendon and ligament repair necessitate the identification of a suitable and effective candidate for cell-based therapy to promote tendon regeneration. Mesenchymal stromal cells (MSCs) have been explored as a potential tissue engineering strategy for tendon repair. While they are multipotent and have regenerative potential in vivo, they are limited in their self-renewal capacity and exhibit phenotypic heterogeneity. Induced pluripotent stem cells (iPSCs) can circumvent these limitations due to their high self-renewal capacity and unparalleled developmental plasticity. In tenocyte development, Scleraxis (Scx) is a crucial direct molecular regulator of tendon differentiation. Additionally, mechanoregulation has been shown to be a central element guiding embryonic tendon development and healing. As such, we have developed a protocol to encapsulate the synergistic effect of biological and mechanical stimulation that may be essential for generating tenocytes. iPSCs were induced to become mesenchymal stromal cells (iMSCs) and were characterized with classic mesenchymal stromal cell markers via flow cytometry. Next, using a lentiviral vector, the iMSCs were transduced to stably overexpress SCX (iMSCSCX+). These iMSCSCX+ cells can be further matured into iTenocytes via uniaxial tensile loading using a 2D bioreactor. The resulting cells were characterized by observing the upregulation of early and late tendon markers, as well as collagen deposition. This method of generating iTenocytes can be used to assist researchers in developing a potentially unlimited off-the-shelf allogeneic cell source for tendon cell therapy applications.

Phase-sensitive deep reconstruction method for rapid multiparametric MR fingerprinting and quantitative susceptibility mapping in the brain.

INTRODUCTION: This study explores the potential of Magnetic Resonance Fingerprinting (MRF) with a novel Phase-Sensitivity Deep Reconstruction Network (PS-DRONE) for simultaneous quantification of T1, T2, Proton Density, B1+, phase and quantitative susceptibility mapping (QSM). METHODS: Data were acquired at 3 T in vitro and in vivo using an optimized EPI-based MRF sequence. Phantom experiments were conducted using a standardized phantom for T1 and T2 maps and a custom-made agar-based gadolinium phantom for B1 and QSM maps. In vivo experiments included five healthy volunteers and one patient diagnosed with brain metastasis. PSDRONE maps were compared to reference maps obtained through standard imaging sequences. RESULTS: Total scan time was 2 min for 32 slices and a resolution of [1 mm, 1 mm, 4.5 mm]. The reconstruction of T1, T2, Proton Density, B1+ and phase maps were reconstructed within 1 s. In the phantoms, PS-DRONE analysis presented accurate and strongly correlated T1 and T2 maps (r = 0.99) compared to the reference maps. B1 maps from PS-DRONE showed slightly higher values, though still correlated (r = 0.6) with the reference. QSM values showed a small bias but were strongly correlated (r = 0.99) with reference data. In the in vivo analysis, PS-DRONE-derived T1 and T2 values for gray and white matter matched reference values in healthy volunteers. PS-DRONE B1 and QSM maps showed strong correlations with reference values. CONCLUSION: The PS-DRONE network enables concurrent acquisition of T1, T2, PD, B1+, phase and QSM maps, within 2 min of acquisition time and 1 s of reconstruction time.

A video-based decision aid improved knowledge and decreased decisional conflict for asymptomatic persistent endodontic lesions.

AIM: This prospective cohort study aimed to (i) evaluate patients' treatment decisions, decisional conflict and knowledge levels before and after use of a video-based decision aid (DA) on asymptomatic persistent endodontic lesions (APEL) and to (ii) elicit important decision factors for patients in the decision-making process. METHODOLOGY: A video DA modelled after the International Patient Decision Aids Standards (IPDAS) was designed. The video was pilot-tested, revised and used on 50 patients referred to the graduate endodontic clinic and presenting with an incidental finding of APEL detected on radiographs, with informed consent (DSRB 2020/00133). Recruitment was conducted from June 2020 to November 2021. Patients' treatment decisions and decision-making process were studied. Patients also completed a questionnaire on knowledge gain, decisional conflict and confidence levels. RESULTS: Forty-three patients (48 teeth) out of 50 patients chose long-term monitoring of APEL while 7 patients (7 teeth) decided on endodontic intervention. Median knowledge scores increased from 58.3 (IQR: 41.7, 75.0) to 87.5 (IQR: 75.0, 100.0) (p < .001); median decisional conflict scale (DCS) scores decreased from 25.0 (IQR: 12.5, 34.4) to 3.1 (IQR: 0, 23.8) (p < .001), and 44 (88%) patients were confident or very confident with their treatment decisions. Statistical analyses showed that asymptomatic condition of tooth was the sole decision factor with statistical significance while socioeconomic factors (age, gender, race, education and income levels) showed no significant trend. CONCLUSIONS: The majority of patients presenting with APEL in this study chose long-term monitoring over immediate intervention. Using the video-based DA in the decision-making process significantly improved patients' knowledge and decreased their decisional conflict levels.

The Use of Magnetic Resonance Imaging in Radiation Therapy Treatment Simulation and Planning.

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Prevalence of Comprehensive Eye Examination in Preschool Children With Eye Conditions.

Introduction: The purpose of this study is to assess the prevalence of comprehensive eye examinations in multiethnic preschool children, including children with visually significant eye conditions, and identify factors associated with comprehensive eye examinations. Methods: A sample of 9,197 African American, Hispanic, Asian American, and non-Hispanic White children aged 6-72 months was recruited for the Multi-Ethnic Pediatric Eye Disease Study from 2003 to 2011. Logistic regression performed in 2022 identified independent factors associated with parent-reported history of comprehensive eye examinations. The proportion of children with previous comprehensive eye examinations and the proportion with undetected amblyopia or strabismus were measured. Results: The prevalence of comprehensive eye examinations was 6.3% overall and 38.3%, 24.8%, 19.1%, 15.1%, and 9.8% among children with strabismus, amblyopia, significant anisometropia, hyperopia, and astigmatism, respectively. Children without prior comprehensive eye examinations were more likely to have undetected amblyopia or strabismus than those with comprehensive eye examination history (ps<0.001). The prevalence of comprehensive eye examinations was higher among older children. Prevalence varied by race/ethnicity, with 8.1%, 7.9%, 6.3%, and 4.9% of non-Hispanic White, Asian American, African American, and Hispanic children having had prior comprehensive eye examinations, respectively; however, the differences did not remain after adjusting for other associated factors. Older age, a primary caregiver with a college/university degree or higher, having vision insurance, gestational age <33 weeks, neurodevelopmental disorder diagnosis, strabismus, and ocular disease history were all statistically significantly associated with a relatively higher prevalence of comprehensive eye examinations in multivariable analyses. Conclusions: Comprehensive eye examinations were uncommon among preschool children, including those with treatable vision disorders. Interventions, such as parent education and vision insurance, are needed to imaprove comprehensive eye examination access and utilization for at-risk preschool children.

Retinal perfusion is linked to cognition and brain MRI biomarkers in Black Americans.

INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.

Prolonged operative time predicts postoperative deep venous thrombosis in head and neck cancer patients who undergo free flap reconstruction.

Objective: This study sought to quantify the deep venous thrombosis (DVT) incidence in head and neck cancer (HNC) patients undergoing free tissue transfer and to identify independent predictors of postoperative DVT. Materials and Methods: This is a cross-sectional study of the National Surgical Quality Improvement Program database from 2010 through 2020. The sample included all HNC surgical patients treated with free flap reconstruction. The study outcome was the presence of a DVT requiring treatment within 30 days of surgery. Univariate analyses were performed using chi-squared and independent t-tests. A multiple logistic regression model was created using all significant univariate predictors. Results: A total of 3954 patients were identified, of whom 53 (1.3%) experienced a postoperative DVT. The only medical comorbidity associated with DVT was COPD (RR = 2.7 [1.3, 5.4]; p < .01). Operative time longer than 9 hours (RR = 1.9 [1.0, 3.2]; p = .04) and length of stay longer than 10 days (RR = 1.9 [1.1, 3.2]; p = .02) were associated with greater DVT rates. In the multivariate analysis, only COPD (p < .01) and operative time (p = .02) were independently associated with DVT risk. The presence of a DVT was found to increase the relative risk of readmission (RR = 2.1 [1.2, 3.6]; p < .01) and non-home disposition (RR = 2.4 [1.7, 3.5]; p < .01). Conclusions: The incidence of DVT in HNC free flap patients was comparable to what has been reported in the general population of HNC surgery patients. Operative time >9 h and COPD history were independent risk factors for DVT in this subset of patients. Symptomatic DVTs necessitating treatment were accompanied by poorer post-hospitalization outcomes. Level of Evidence: Level 3.

Experimental Modeling of Host-Bacterial Interactions in Head and Neck Squamous Cell Carcinoma.

The microscopic species colonizing the human body, collectively referred to as the microbiome, play a crucial role in the maintenance of tissue homeostasis, immunity, and the development of disease. There is evidence to suggest associations between alterations in the microbiome and the development of head and neck squamous cell carcinomas (HNSCC). The use of two-dimensional (2D) modeling systems has made significant strides in uncovering the role of microbes in carcinogenesis; however, direct mechanistic links remain in their infancy. Patient-derived three-dimensional (3D) HNSCC organoid and organotypic models have recently been described. Compared to 2D models, 3D organoid culture systems effectively capture the genetic and epigenetic features of parent tissue in a patient-specific manner and may offer a more nuanced understanding of the role of host-microbe responses in carcinogenesis. This review provides a topical literature review assessing the current state of the field investigating the role of the microbiome in HNSCC; including in vivo and in vitro modeling methods that may be used to characterize microbiome-epithelial interactions.

Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma.

(1) Background: The role of rare immune cell subtypes in many solid tumors, chief among them head and neck squamous cell carcinoma (HNSCC), has not been well defined. The objective of this study was to assess the association between proportions of common and rare immune cell subtypes and survival outcomes in HNSCC. (2) Methods: In this cohort study, we utilized a deconvolution approach based on the CIBERSORT algorithm and the LM22 signature matrix to infer proportions of immune cell subtypes from 517 patients with untreated HPV-negative HNSCC from The Cancer Genome Atlas. We performed univariate and multivariable survival analysis, integrating immune cell proportions with clinical, pathologic, and genomic data. (3) Results: We reliably deconvolved 22 immune cell subtypes in most patients and found that the most common immune cell types were M0 macrophages, M2 macrophages, and memory resting CD4 T cells. In the multivariable analysis, we identified advanced N stage and the presence of γδ T cells as independently predictive of poorer survival. (4) Conclusions: We uncovered that γδ T cells in the tumor microenvironment were a negative predictor of survival among patients with untreated HNSCC. Our findings underscore the need to better understand the role of γδ T cells in HNSCC, including potential pro-tumorigenic mechanisms, and whether their presence may predict the need for alternative therapy approaches.

Retention of Human iPSC-Derived or Primary Cells Following Xenotransplantation into Rat Immune-Privileged Sites.

In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.

Predicting Overall Survival for Patients with Malignant Mesothelioma Following Radiotherapy via Interpretable Machine Learning.

PURPOSE/OBJECTIVES: Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer arising from the cells of the thoracic pleura with a poor prognosis. We aimed to develop a model, via interpretable machine learning (ML) methods, predicting overall survival for MPM following radiotherapy based on dosimetric metrics as well as patient characteristics. MATERIALS/METHODS: Sixty MPM (37 right, 23 left) patients treated on a Tomotherapy unit between 2013 and 2018 were retrospectively analyzed. All patients received 45 Gy (25 fractions). The multivariable Cox regression (Cox PH) model and Survival Support Vector Machine (sSVM) were applied to build predictive models of overall survival (OS) based on clinical, dosimetric, and combined variables. RESULTS: Significant differences in dosimetric endpoints for critical structures, i.e., the lung, heart, liver, kidney, and stomach, were observed according to target laterality. The OS was found to be insignificantly different (p = 0.18) between MPM patients who tested left- and right-sided, with 1-year OS of 77.3% and 75.0%, respectively. With Cox PH regression, considering dosimetric variables for right-sided patients alone, an increase in PTV_Min, Total_Lung_PTV_Mean, Contra_Lung_Volume, Contra_Lung_V20, Esophagus_Mean, and Heart_Volume had a greater hazard to all-cause death, while an increase in Total_Lung_PTV_V20, Contra_Lung_V5, and Esophagus_Max had a lower hazard to all-cause death. Considering clinical variables alone, males and increases in N stage had greater hazard to all-cause death; considering both clinical and dosimetric variables, increases in N stage, PTV_Mean, PTV_Min, and esophagus_Mean had greater hazard to all-cause death, while increases in T stage and Heart_V30 had lower hazard to all-cause-death. In terms of C-index, the Cox PH model and sSVM performed similarly and fairly well when considering clinical and dosimetric variables independently or jointly. CONCLUSIONS: Clinical and dosimetric variables may predict the overall survival of mesothelioma patients, which could guide personalized treatment planning towards a better treatment response. The identified predictors and their impact on survival offered additional value for translational application in clinical practice.

Corrigendum: A review of the peripheral proprioceptive apparatus in the larynx.

[This corrects the article DOI: 10.3389/fnana.2023.1114817.].

Protocol for tumor dissociation and fluorescence-activated cell sorting of human head and neck cancers.

Tumors originating from the head and neck represent diverse histologies and are comprised of several cell types, including malignant cells, cancer-associated fibroblasts, endothelial cells, and immune cells. In this protocol, we describe a step-by-step approach for the dissociation of fresh human head and neck tumor specimens, followed by isolation of viable single cells using fluorescence-activated cell sorting. Our protocol facilitates the effective downstream use of techniques, including single-cell RNA sequencing and generation of three-dimensional patient-derived organoids. For complete details on the use and execution of this protocol, please refer to Puram et al. (2017)1 and Parikh et al. (2022).2.

Single Cell Transcriptomics-Informed Induced Pluripotent Stem Cells Differentiation to Tenogenic Lineage.

During vertebrate embryogenesis, axial tendons develop from the paraxial mesoderm and differentiate through specific developmental stages to reach the syndetome stage. While the main roles of signaling pathways in the earlier stages of the differentiation have been well established, pathway nuances in syndetome specification from the sclerotome stage have yet to be explored. Here, we show stepwise differentiation of human iPSCs to the syndetome stage using chemically defined media and small molecules that were modified based on single cell RNA-sequencing and pathway analysis. We identified a significant population of branching off-target cells differentiating towards a neural phenotype overexpressing Wnt. Further transcriptomics post-addition of a WNT inhibitor at the somite stage and onwards revealed not only total removal of the neural off-target cells, but also increased syndetome induction efficiency. Fine-tuning tendon differentiation in vitro is essential to address the current challenges in developing a successful cell-based tendon therapy.

Quantitative longitudinal mapping of radiation-treated prostate cancer using MR fingerprinting with radial acquisition and subspace reconstruction.

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the acquisition. Iterative reconstruction with the subspace model and additional regularization of the signal representation in the subspace is performed to minimize the number of spokes and maintain matching quality and SNR. Reconstruction accuracy was assessed using the ISMRM NIST phantom. In-vivo validation was performed on two healthy subjects and two prostate cancer patients undergoing radiation therapy. The longitudinal repeatability was quantified using the concordance correlation coefficient (CCC) in one of the healthy subjects by repeated scans over 1 year. One prostate cancer patient was scanned at three time points, before initiating therapy and following brachytherapy and external beam radiation. Changes in the T1/T2 maps obtained with the proposed method were quantified. The prostate, peripheral and transitional zones, and visible dominant lesion were delineated for each study, and the statistics and distribution of the quantitative mapping values were analyzed. Significant image quality improvements compared with standard reconstruction methods were obtained with the proposed subspace reconstruction method. A notable decrease in the spread of the T1/T2 values without biasing the estimated mean values was observed with the subspace reconstruction and agreed with reported literature values. The subspace reconstruction enabled visualization of small differences in T1/T2 values in the tumor region within the peripheral zone. Longitudinal imaging of a volunteer subject yielded CCC of 0.89 for MRF T1, and 0.81 for MRF T2 in the prostate gland. Longitudinal imaging of the prostate patient confirmed the feasibility of capturing radiation treatment related changes. This work is a proof-of-concept for a high resolution and fast quantitative mapping using golden-angle radial MRF combined with a subspace reconstruction technique for longitudinal treatment response assessment in subjects undergoing radiation treatment.

A review of the peripheral proprioceptive apparatus in the larynx.

The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx.

Smoking and Head and Neck Cancer.

This Patient Page describes the association of tobacco use with head and neck cancer and provides suggested treatment and prevention measures.

iPSC-derived tenocytes seeded on microgrooved 3D printed scaffolds for Achilles tendon regeneration.

Tendons and ligaments have a poor innate healing capacity, yet account for 50% of musculoskeletal injuries in the United States. Full structure and function restoration postinjury remains an unmet clinical need. This study aimed to assess the application of novel three dimensional (3D) printed scaffolds and induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) overexpressing the transcription factor Scleraxis (SCX, iMSCSCX+ ) as a new strategy for tendon defect repair. The polycaprolactone (PCL) scaffolds were fabricated by extrusion through a patterned nozzle or conventional round nozzle. Scaffolds were seeded with iMSCSCX+ and outcomes were assessed in vitro via gene expression analysis and immunofluorescence. In vivo, rat Achilles tendon defects were repaired with iMSCSCX+ -seeded microgrooved scaffolds, microgrooved scaffolds only, or suture only and assessed via gait, gene expression, biomechanical testing, histology, and immunofluorescence. iMSCSCX+ -seeded on microgrooved scaffolds showed upregulation of tendon markers and increased organization and linearity of cells compared to non-patterned scaffolds in vitro. In vivo gait analysis showed improvement in the Scaffold + iMSCSCX+ -treated group compared to the controls. Tensile testing of the tendons demonstrated improved biomechanical properties of the Scaffold + iMSCSCX+ group compared with the controls. Histology and immunofluorescence demonstrated more regular tissue formation in the Scaffold + iMSCSCX+ group. This study demonstrates the potential of 3D-printed scaffolds with cell-instructive surface topography seeded with iMSCSCX+ as an approach to tendon defect repair. Further studies of cell-scaffold constructs can potentially revolutionize tendon reconstruction by advancing the application of 3D printing-based technologies toward patient-specific therapies that improve healing and functional outcomes at both the cellular and tissue level.