Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

Tendon healing after injury is relatively slow, mainly because of the weak activity and metabolic properties of tendon cells (tenocytes). Bletilla striata polysaccharide (BSP) has been reported to enhance cell proliferation. Here, we aimed to increase tendon cell proliferation by BSP treatment. We isolated tenocytes from the flexor tendon of human origin. Moreover, we improved the process of extracting BSP. When human tenocytes (HTs) were treated with 100 μg/mL BSP, the MEK/ERK1/2 and PI3K/Akt signaling pathways were activated, thereby enhancing the proliferation ability of tenocytes. BSP treatment also increased the migration of HTs and their ability to secrete the extracellular matrix (Col-I and Col-III). In conclusion, BSP was successfully extracted from a natural Chinese herbal extract and was shown to enhance tenocytes proliferation, migration and collagen release ability. This study is the first to demonstrate improved healing of tendons using BSP.

In this study, we prepared core-sheath nanofiber membranes (CSNFMs) with silver nanoparticles (Ag NPs) embedding in the polylactic acid (PLA) nanofiber sheath and hyaluronic acid (HA) in the nanofiber core. The PLA/Ag NPs sheath provides mechanical support as well as anti-bacterial and anti-inflammatory properties. The controlled release of HA from the core could exert anti-adhesion effects to promote tendon sliding while reducing fibroblast attachment. From the microfibrous structural nature of CSNFMs, they function as barrier membranes to reduce fibroblast penetration without hampering nutrient transports to prevent post-operative peritendinous adhesion. As the anti-adhesion efficacy will depend on release rate of HA from the core as well as Ag NP from the sheath, we fabricated CSNFMs of comparable fiber diameter, but with thick (Tk) or thin (Tn) sheath. Similar CSNFMs with thick (Tk⁺) and thin (Tn⁺) sheath but with embedded Ag NPs in the sheath were also prepared. The physico-chemical properties of the barrier membranes were characterized in details, together with their biological response including cell penetration, cell attachment and proliferation, and cytotoxicity. Peritendinous anti-adhesion models in rabbits were used to test the efficacy of CSNFMs as anti-adhesion barriers, from gross observation, histology, and biomechanical tests. Overall, the CSNFM with thin-sheath and Ag NPs (Tn⁺) shows antibacterial activity with low cytotoxicity, prevents fibroblast penetration, and exerts the highest efficacy in reducing fibroblast attachment in vitro. From in vivo studies, the Tn⁺ membrane also shows significant improvement in preventing peritendinous adhesions as well as anti-inflammatory efficacy, compared with Tk and Tn CSNFMs and a commercial adhesion barrier film (SurgiWrap^®) made from PLA.

Peritendinous adhesion is a major complication after tendon injury and the subsequent repairs or reconstructions. The degree of adhesion can be reduced by the interposition of a membranous barrier between the traumatized tendon and the surrounding tissue. In the present study, electrospun water-borne polyurethane (WPU) nanofibrous membranes (NFMs) were created for use after the reparation or reconstruction of tendons to reduce adhesion. In the electrospinning process, water was employed as the solvent for WPU, and this solvent was ecofriendly and nontoxic. The nanofibrous architecture and pore size of the WPU NFMs were analyzed. Their microporosity (0.78–1.05 µm) blocked the penetration of fibroblasts, which could result in adhesion and scarring around the tendon during healing. The release of WPU mimicked the lubrication effect of the synovial fluid produced by the synovium around the tendon. In vitro cell studies revealed that the WPU NFMs effectively reduced the number of fibroblasts that became attached and that there was no significant cytotoxicity. In vivo studies with the rabbit flexor tendon repair model revealed that WPU NFMs reduced the degree of peritendinous adhesion, as determined using a gross examination; a histological cross section evaluation; and measurements of the range of motion of interphalangeal joints (97.1 ± 14.7 and 79.0 ± 12.4 degrees in proximal and distal interphalangeal joints respectively), of the length of tendon excursion (11.6 ± 1.9 cm), and of the biomechanical properties.

Background: The prognosis of high ulnar nerve injury is poor despite nerve repair or grafting. Anterior interosseous nerve (AIN) transfers provide a satisfactory recovery. However, the efficacy of end-to-side (ETS) AIN transfer and optimal timing in Sunderland grade IV/V of high ulnar nerve injury is lacking. Objective: The goals were to compare the outcomes of high ulnar nerve injury managed with ETS AIN transfers with those managed with conventional procedures (nerve repair or graft only) and identify differences between early and delayed transfers. Methods: Patients with isolated high ulnar nerve injury (Sunderland grade IV/V) from 2010 to 2017 were recruited. Patients with conventional treatments and AIN transfers were designated as the control and AIN groups, respectively. Early transfer was defined as the AIN transfer performed within 8 weeks postinjury. Outcomes were measured and analyzed by the British Medical Research Council (BMRC) score, grip strength, and pinch strength. Results: A total of 24 patients with high ulnar nerve injury (Sunderland grade IV/V) were included. There were 11 and 13 patients in the control and AIN groups, respectively. In univariate analysis, both early and delayed AIN transfers demonstrated significantly better motor recovery among BMRC score and strength of grip and pinch at 12 months (P < 0.05). No statistical significance was found between early and delayed transfer. In multivariate analysis, both early and delayed transfers were regarded as strong and independent factors for motor recovery of ulnar nerve. Compared with the control, early [odds ratio (OR), 1.83; P < 0.001] and delayed (OR, 1.59; P < 0.001) transfers showed significant improvement with regard to BMRC scores. The pinch strength in early (OR, 31.68; P < 0.001) and delayed (OR, 26.45; P < 0.001) transfers was also significantly better. Conclusion: The ETS AIN transfer, in either early or delayed fashion, significantly improved intrinsic motor recovery in high ulnar nerve injuries classified as Sunderland grade IV/V. The early transfer group demonstrated a trend toward better functional recovery with less downtime.

This study measured three-dimensional facial fluctuating asymmetry in 600 normal and healthy Taiwanese individuals (6 to 12 years old) and assessed the perceptions of increasing levels of facial fluctuating asymmetric severity by using a panel composed of 20 clinicians (surgical professionals), as well as 20 adult and 40 pre-adolescent observers. On average, this normal cohort presented a facial fluctuating asymmetry of 0.96 ± 0.52 mm, with 0.52 ± 0.05, 0.67 ± 0.09, 1.01 ± 0.10, and 1.71 ± 0.36 mm for levels I, II, III, and IV of severity, respectively. For all categories of raters, significant differences in the average symmetry–asymmetry scale values were observed, with level I < level II < level III = level IV (all p < 0.01, except for level III vs. IV comparisons with p > 0.05). For level I, pre-adolescent observers presented a significantly (p < 0.05) higher symmetry–asymmetry scale value than adult observers, with no significant (all p > 0.05) differences for other comparisons. For overall facial asymmetry and levels II, III, and IV, no significant (all p > 0.05) differences were observed. This study reveals that the normal pediatric face is asymmetric and the panel assessment of facial fluctuating asymmetry was influenced by the level of severity and the category of raters and contributes to the literature by revealing that pre-adolescent raters present a similar or higher perception of facial asymmetry than adult raters.