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Tendons serve to attach muscles to bones, and are dense structures composed offibers. Tendon injuries, as well as tendinopathies, in which a tendon is overused or hasbeen degenerated due to sport injuries or age, are a large problem for many adult patientsand account for about 30% of musculoskeletal diseases. Around 33 millionmusculoskeletal injuries have been reported per year in the United States alone, 50% ofwhich involve tendon and ligament injuries. In American healthcare, only the flexortendon lacerations sustain estimated costs of anywhere between $240.8 to $409.1 millionper year. Having a slow metabolism, tendon tissue needs a substantial period to redevelopenough strength after injury. In most of the cases, tendon tissue does not have fullfunctional recovery because of low regeneration capacity and scar tissue formation.Therefore, the healing of tendon injuries is a significant and clinically challengingproblem requiring an urgent need to find alternative and cost-effective treatments. Toaddress this problem, a combinatorial approach involving synergetic use of a 3-dimensional (3D) scaffold system with adult mesenchymal stem cells (MSCs) and locallyapplied electrical stimulation (ES) was used to produce bioactive extracellular vesicles(EVs) as novel therapeutic tools to enhance tendon regeneration. For this purpose, wheyprotein isolate (WPI)-based 3D scaffolds were developed to provide favorablemicroenvironment for MSCs attachment and growth. Conductive graphene andbiodegradable Polylactic Acid (PLA) based flexible electronic coil was integrated to the 3D WPI scaffold to provide wireless ES of MSCs and modulate EVs secretion. Theisolated EVs were characterized and applied to primary tenocyte cells to evaluate theregenerative activity. The results indicated that the isolated EVs, as well as applied ES,promoted the regeneration capacity of tenocyte cells in vitro and promoted the expressionof tendon markers. This research demonstrated the proof of concept for potential use ofEVs as therapeutic tools for tendon regeneration and can have important impacts inadvancing the tissue regeneration field by offering a less invasive and more effectivetreatment option for tendon injuries, eventually bringing relief to millions of patients.

Abstract: OBJECTIVE: To analyze the relationship between the impacted maxillary canine and the root inclination of the adjacent maxillary incisors. While earlier literature relied on 2-dimensional radiographs, which display an overlapped representation of the maxillary incisors, this project had the advantage of using 3-dimensional imaging to measure each maxillary incisor root inclination independently. METHODS: CBCTs of 27 patients with palatally impacted maxillary canines (group P), 15 patients with buccally impacted canines (group B), and 30 patients with normally erupting maxillary canines (group C) were used in our analysis. Incisor root inclination with respect to the palatal plane was measured for each individual maxillary incisor, and an ANOVA was used to assess significant differences for each incisor between the 3 groups. Paired T-tests were conducted in groups P and B to evaluate whether or not lateral or central incisors on the side of the impacted canine showed significant differences in inclination from their contralateral counterparts. Factors such as distance away from the adjacent lateral incisor, vertical position of the canine crown, and impaction sector were recorded for each patient in groups P and B. These factors were included in Pearson correlation analyses also considering the adjacent lateral incisor’s root inclination. All three statistical analyses were repeated after patients with peg-shaped/small maxillary lateral incisors were removed from the groups (3 in group P, 2 in group B, 1 in group C). RESULTS: Compared to group C, lateral incisors on the side of the palatally impacted canine showed an average of approximately 10 degrees more buccal root inclination, and central incisors on the affected side averaged about 5 degrees more buccal root inclination. Group B showed significant differences in the ipsilateral lateral incisor alone, which averaged 12 more degrees of palatal root inclination when compared to group C. Within group P, the ipsilateral lateral incisor averaged 7.5 more degrees of buccal root inclination than its contralateral counterpart. In comparison, the central incisor on the affected side averaged 3 degrees more buccal root inclination than that of the contralateral side. In group B, the lateral incisor immediately adjacent to the buccally impacted canine displayed an average of approximately 10.5 degrees more palatal root inclination than the contralateral side. In group P, moderate correlations revealed that the closer and more coronally positioned the impacted canine is with respect to the lateral incisor, the more buccally inclined the lateral incisor’s root will be. A moderate correlation also showed that the more medially displaced the palatally impacted canine is situated (i.e., the higher the impaction sector), the more buccally inclined the adjacent lateral incisor’s root would be. In group B, a considerable correlation showed that the more medial the impacted canine was, the more palatally inclined the root of the lateral incisor would be, however this finding should be interpreted with caution since only two cases in group B had their canines situated in impaction sector 4-5. After peg-shaped/small laterals were removed, group P no longer showed significant differences in ipsilateral central incisor inclination compared to group C. Furthermore, the variable of impaction sector no longer shared a significant correlation with incisor root inclination in group P. Additionally, average root inclinations of all maxillary incisors demonstrated less buccal root inclination in group P and less palatal root inclination in group B. CONCLUSION: Patients with impacted maxillary canines do not show significant differences in the root position of all four maxillary incisors, but only in the incisors on the side of the impacted canine. While palatal impactions are associated with buccally positioned roots of both the ipsilateral lateral and central incisors (with different degrees of inclination), buccal impactions are only associated with palatally placed roots of the ipsilateral lateral incisors.