Effects of jaw opening exercise on aspiration in stroke patients with dysphagia: a pilot study.

[Purpose] The purpose of this study was to investigate the effect of jaw opening exercise (JOE) on aspiration in patients with dysphagia after stroke. [Subjects and Methods] Three subjects were recruited. Isometric and isotonic JOE were performed using a rubber ball, 5 days a week for 4 weeks. Aspiration was evaluated using the penetration-a spiration scale (PAS) based on a videofluoroscopic swallowing study. [Results] All subjects showed a score reduction of at least 1 point and a maximum reduction of 2 points in the PAS in the liquid type. [Conclusion] This study confirmed that JOE can be used to reduce aspiration in patients with dysphagia after stroke.

Injectable Dual Fenton/Enzymatically Cross-Linked Double-Network Hydrogels Based on Acrylic/Phenolic Polymers with Highly Reinforced and Tunable Mechanical Properties.

Injectable hydrogels have been extensively used as promising therapeutic scaffolds for a wide range of biomedical applications, such as tissue regeneration and drug delivery. However, their low fracture toughness and brittleness often limit their scope of application. Double-network (DN) hydrogel, which is composed of independently cross-linked rigid and ductile polymer networks, has been proposed as an alternative technique to compensate for the weak mechanical properties of hydrogels. Nevertheless, some challenges still remain, such as the complicated and time-consuming process for DN formation, and the difficulty in controlling the mechanical properties of DN hydrogels. In this study, we introduce a simple, rapid, and controllable method to prepare in situ cross-linkable injectable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton's reagent, the DN hydrogels were rapidly formed with controllable gelation rate. Importantly, the DN hydrogels showed a 13-fold increase in compressive strength and a 14-fold increase in tensile strength, compared to the single network hydrogels. The mechanical properties, elasticity, and plasticity of DN hydrogels could also be modulated by simply varying the preparation conditions, including the cross-linking density and reagent concentrations. At low cross-linker concentration (<0.05 wt %), the plastic DN hydrogel stretched to over 6,500%, whereas high cross-linker concentration (≥0.05 wt %) induced fully elastic hydrogels, without hysteresis. Besides, DN hydrogels were endowed with rapid self-recovery and highly enhanced adhesion, which can be further applied to wearable devices. Moreover, human dermal fibroblasts treated with DN hydrogels retained viability, demonstrating the biocompatibility of the cross-linking system. Therefore, we expect that the dual Fenton-/enzyme-mediated cross-linkable DN hydrogels offer great potential as advanced biomaterials applied for hard tissue regeneration and replacement.

Gelatin microgel-coated balloon catheter with enhanced delivery of everolimus for long-term vascular patency.

In-stent restenosis (ISR) after percutaneous coronary intervention is a major reason for limited long-term patency due to complex neointimal proliferation caused by vascular injury. Drug-coated balloon (DCB) has been developed to treat various cardiovascular diseases including ISR by providing anti-proliferative drugs into blood vessel tissues. However, a significant proportion of the drug is lost during balloon tracking, resulting in ineffective drug delivery to the target region. In this study, we report an everolimus-coated balloon (ECB) using everolimus-loaded gelatin-hydroxyphenyl propionic acid microgel (GM) with enhanced everolimus delivery to vascular walls for long-term patency. GM with high drug loading (> 97%) was simply prepared by homogenizing enzyme-mediated crosslinked hydrogels. The optimal condition to prepare GM-coated ECB (GM-ECB) was established by changing homogenization time and ethanol solvent concentration (30 ∼ 80%). In vitro sustained everolimus release for 30 d, and cellular efficacy using smooth muscle cells and vascular endothelial cells were evaluated. Additionally, an in vivo drug transfer levels of GM-ECB using rabbit femoral arteries were assessed with reduced drug loss and efficient drug delivery capability. Finally, using ISR-induced porcine models, effective in vivo vascular patency 4 weeks after treatment of ECBs was also confirmed. Thus, this study strongly demonstrates that GM can be used as a potential drug delivery platform for DCB application. STATEMENT OF SIGNIFICANCE: We report an ECB using everolimus-loaded GM prepared by homogenization of enzymatic cross-linked hydrogel. GM showed efficient drug loading (> 97 %) and controllable size. GM-ECB exhibited potential to deliver everolimus in a sustained manner to target area with drug efficacy and viability against SMC and EC. Although GM-ECB had much lower drug content compared to controls, animal study demonstrated enhanced drug transfer and reduced drug loss of GM-ECB due to the protection of encapsulated drugs by GM, and the possible interaction between GM and endothelium. Finally, vascular patency and safety were assessed using ISR-induced porcine models. We suggest an advanced DCB strategy to alleviate rapid drug clearance by bloodstream while improving drug delivery for a long-term vascular patency.

Synthesis and characterizations of in situ cross-linkable gelatin and 4-arm-PPO-PEO hybrid hydrogels via enzymatic reaction for tissue regenerative medicine.

In situ cross-linkable hybrid hydrogels composed of gelatin and 4-arm-polypropylene oxide-polyethylene oxide (Tetronic) was developed as an injectable scaffold for tissue regeneration. The gelatin was modified by hydroxyphenyl propionic acid (HPA) and the Tetronic was conjugated with tyramines (Tet-TA). The hydrogels were rapidly formed by mixing the polymer solutions containing horseradish peroxidase (HRP) and hydrogen peroxide (H(2)O(2)). The gelation time and mechanical properties of the hydrogels could be controlled by varying the HRP and H(2)O(2) concentrations. In vitro degradation study of the hybrid hydrogels was carried out using collagenase and the prolonged proteolytic degradation was obtained due to the presence of the Tetronic. Human dermal fibroblast (hDFB) was cultured in the hydrogel matrices to evaluate the cyto-compatibility. The encapsulated cells were shown to be highly viable and spread over the gel matrices, suggesting that the hybrid hydrogels have an excellent cyto-compatibility. The hydrogels were also subcutaneously injected in the back of mice and the results demonstrated that the hydrogels were rapidly formed at the injected site. From these results, we demonstrate that the in situ cross-linkable hydrogels formed by hybridization of gelatin and Tetronic via enzyme-mediated reactions hold great promise for use as injectable matrices for tissue regenerative medicine due to their tunable physico-chemical properties and excellent bioactivity.

The effect of neuromuscular electrical stimulation with different electrode positions on swallowing in stroke patients with oropharyngeal dysphagia: A randomized trial.

OBJECTIVE: To examine the effects of neuromuscular electrical stimulation (NMES) on oropharyngeal swallowing function according to 2 types of placement, acting as assistance and as resistance, in stroke patients with dysphagia. METHODS: Thirty-eight stroke patients with dysphasia were randomly assigned to the suprahyoid group (SMG), or infrahyoid muscle group (IMG); 26 patients completed the intervention and were included in the analysis. In the SMG, the electrodes were placed on the region between the jaw and the hyoid bone, whereas in the IMG, the electrodes were placed on the region below the hyoid for the targeted infrahyoid muscles. Both groups received NMES for 30 min/d, 5 d/wk, for 4 weeks and conventional dysphagia therapy. Swallowing function was measured using the Videofluoroscopic Dysphagia Scale and Penetration-Aspiration Scale based on videofluoroscopic swallowing study. Oral dietary intake was measured using the Functional Oral Intake Scale. RESULTS: Both groups showed significant improvements in oropharyngeal function and level of functional oral intake, but there was no significant difference between the two groups. However, the SMG showed a more reduced penetration-aspiration, compared with the IMG. CONCLUSIONS: Altogether, these data demonstrate that 2 types of NMES placements have a similar effect on improving swallowing function and oral diet intake in patients with dysphagia.

Effect of chin tuck against resistance exercise on patients with dysphagia following stroke: A randomized pilot study.

BACKGROUND: Recently, chin tuck against resistance exercise (CTAR) has been reported as a remedial treatment for pharyngeal dysphagia. However, the clinical evidence of the effect is still lacking. OBJECTIVE: This study investigated the effect of CTAR on the swallowing function in patients with dysphagia following subacute stroke. METHODS: The patients were randomly assigned to an experimental (n = 11) or a control group (n = 11). The experimental group performed CTAR using the CTAR device. The control group received only conventional dysphagia treatment. Both groups received training on five days a week, for four weeks. The swallowing function was measured using functional dysphagia scale (FDS) and penetration-aspiration scale (PAS), based on a videofluoroscopic swallowing study (VFSS). RESULTS: The experimental group showed more improvements in the oral cavity, laryngeal elevation/epiglottic closure, residue in valleculae, and residue in pyriform sinuses of FDS and PAS compared to the control group (p < 0.05, all). CONCLUSIONS: This study demonstrated that CTAR is effective in improving the pharyngeal swallowing function in patients with dysphagia after stroke. Therefore, we recommend CTAR as a new remedial training alternative to HLE.