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Critical-sized bone defects can lead to significant morbidity, and interventions are limited by the availability and donor-site morbidity of bone grafts. Polymer scaffolds seeded with cells have been explored to replace bone grafts. Adipose-derived stem cells have shown great promise for vascularization and osteogenesis of these constructs, and cocultures of differentiated stem cells are being explored to augment vessel and bone formation. Adipose-derived stem cells were differentiated into endothelial cells and osteoblasts, and in vitro studies showed increased proliferation of cocultured cells compared with undifferentiated adipose-derived stem cells and monocultures of endothelial cells and osteoblasts. The cells were seeded into polylactic acid gas-plasma-treated scaffolds as cocultures and monocultures and then implanted into critical-sized rat calvarial defects. The cocultures were in a 1:1 osteoblast to endothelial cell ratio. The increase in proliferation seen by the cocultured cells in vitro did not translate to increased vascularization and osteogenesis in vivo. In vivo, there were trends of increased vascularization in the endothelial cell group and increased osteogenesis in the osteoblast and endothelial monoculture groups, but no increase was seen in the coculture group compared with the undifferentiated adipose-derived stem cells. Endothelial cells enhance vascularization and osteoblast and endothelial cell monocultures enhance bone formation in the polymer scaffold. Predifferentiation of adipose-derived stem cells is promising for improving vascularization and osteogenesis in polymer scaffolds but requires future evaluation of coculture ratios to fully characterize this response.

Objective: To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. Methods: Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. Results: Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. Conclusion: Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds. [ABSTRACT FROM AUTHOR]

Background: Patients with kidney failure are at risk for lethal complications from hyperkalemia. Resuscitation, medications, and hemodialysis are used to mitigate increased potassium (K+) levels in circulating blood; however, these approaches may not always be readily available or effective, especially in a resource limited environment. We tested a sorbent cartridge (KC, K+ontrol CytoSorbents Medical Inc., Monmouth Junction, New Jersey) which contains a resin adsorber for K+. The objective of this study was to test the utility of KC in an ex vivo circulation system. We hypothesized that KC reduces K+ levels in extracorporeal circulation of donor swine whole blood infused with KCl. Methods: A six-hour circulation study was carried out using KC, a NxStage (NxStage Medical, Inc., Lawrence, MA) membrane, blood bag containing heparinized whole blood with KCl infusion, 3/16-inch ID tubing, a peristaltic pump, and flow sensors. The NxStage permeate line was connected back to the main circuit in the Control group (n = 6), creating a recirculation loop. For KC group (n = 6), KC was added to the recirculation loop, and a continuous infusion of KCl at 10 mEq/hour was administered for two hours. Blood samples were acquired at baseline and every hour for 6 h. Results: In the control group, K+ levels remained at ∼9 mmol/L; 9.1 ± 0.4 mmol/L at 6 h. In the KC group, significant decreases in K+ at hour 1 (4.3 ± 0.3 mmol/L) and were sustained for the experiment duration equilibrating at 4.6 ± 0.4 mmol/L after 6 h (p = 0.042). Main loop blood flow was maintained under 400 mL/min; recirculation loop flow varied between 60 and 70 mL/min in the control group and 45–55 mL/min in the KC group. Decreases in recirculation loop flow in KC group required 7% increase of pump RPM. Conclusions: During ex-vivo extracorporeal circulation using donor swine blood, KC removed approximately 50% of K+, normalizing circulating levels. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated a novel injectable, self-setting, osteoconductive, resorbable adhesive that provides immediate implant stabilization. Materials and Methods: Twenty-six large canines had the mandibular second through fourth premolars and the first molar removed bilaterally. After 3 months, oversized osteotomies were prepared with only the apical 2 mm of the implant engaging native bone. One site had a novel resorbable, self-setting, mineral-organic adhesive (TN-SM) placed around the implant, a second site received bone graft, and a third site received only blood clot. Removal torque, standardized radiography, and histology were used to evaluate implant stability and tissue contact after 24 hours, 10 days, and 4 months. Results: Mean removal torque values after 24 hours were 1.4, 1.3, and 22.2 Ncm for the control, bone graft, and mineral-organic adhesive, respectively. After 10 days, these values were 5.7, 6.2, and 45.7 Ncm and at 4 months increased to 88.7, 77.8, and 104.7 Ncm, respectively. Clinical, radiographic, and histologic evaluations showed a lack of inflammatory reaction. Control defects were initially radiolucent in the coronal area; grafted sites revealed particles in the gap, with both conditions gradually filling with bone over time. At 10 days, histologic evaluation demonstrated excellent biocompatibility and intimate contact of mineral-organic adhesive to both the implant and bone, providing an osseointegration-like bond; control sites revealed no bone contact in the defect area, while the bone-grafted sites revealed unattached graft particles. At 4 months, much of the mineral-organic adhesive was replaced with bone; the control and grafted sites had some bone fill, and many of the defects demonstrated no bone-to-implant contact and were filled with soft tissue or isolated graft particles. Conclusion: The mineral-organic adhesive provides immediate (osseointegration-like) and continued implant stabilization over 4 months in sites lacking primary stability. Experimental sites demonstrated maintenance of crestal bone levels adjacent to the mineral-organic adhesive and soft tissue exclusion without the use of membranes in this canine model. These results demonstrate that this novel mineral-organic adhesive can enable implant osseointegration in a site where insufficient native bone exists to allow immediate implant placement. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: Novel laryngotracheal wound coverage devices are limited by complex anatomy, smooth surfaces, and dynamic pressure changes and airflow during breathing. We hypothesize that a bioinspired mucoadhesive patch mimicking how geckos climb smooth surfaces will permit sutureless wound coverage and also allow drug delivery. Study Design: ex‐vivo. Methods: Polycaprolactone (PCL) fibers were electrospun onto a substrate and polyethylene glycol (PEG) – acrylate flocks in varying densities were deposited to create a composite patch. Sample topography was assessed with laser profilometry, material stiffness with biaxial mechanical testing, and mucoadhesive testing determined cohesive material failure on porcine tracheal tissue. Degradation rate was measured over 21 days in vitro along with dexamethasone drug release profiles. Material handleability was evaluated via suture retention and in cadaveric larynges. Results: Increased flocking density was inversely related to cohesive failure in mucoadhesive testing, with a flocking density of PCL‐PEG‐2XFLK increasing failure strength to 6880 ± 1810 Pa compared to 3028 ± 791 in PCL‐PEG‐4XFLK density and 1182 ± 262 in PCL‐PEG‐6XFLK density. The PCL‐PEG‐2XFLK specimens had a higher failure strength than PCL alone (1404 ± 545 Pa) or PCL‐PEG (2732 ± 840). Flocking progressively reduced composite stiffness from 1347 ± 15 to 763 ± 21 N/m. Degradation increased from 12% at 7 days to 16% after 10 days and 20% after 21 days. Cumulative dexamethasone release at 0.4 mg/cm2 concentration was maintained over 21 days. Optimized PCL‐PEG‐2XFLK density flocked patches were easy to maneuver endoscopically in laryngeal evaluation. Conclusions: This novel, sutureless, patch is a mucoadhesive platform suitable to laryngeal and tracheal anatomy with drug delivery capability. Level of Evidence: NA Laryngoscope, 131:1958–1966, 2021 [ABSTRACT FROM AUTHOR]