Therapeutic Engineered Hydrogel Coatings Attenuate the Foreign Body Response in Submuscular Implants.

BACKGROUND: Biomedical devices are implanted into mammalian soft tissues to improve, monitor, or restore form or function. The utility of these implants is limited by the subsequent foreign body response (FBR), beginning with inflammation and terminating in a collagen envelope around the device, known as the capsule. This capsule then can contract and distort the shape of the device or limit its effectiveness in interacting with the surrounding host tissues. In the current study, we investigated the effect of therapeutic collagen-coated silicone discs in a rat model of the FBR. METHODS: A 3-dimensional printed mold was used to fabricate collagen-coated silicone discs incorporating 3 therapeutic agents: colchicine, a function-blocking antibody against interleukin 8 (IL-8) receptor B, and a powerful anti-inflammatory steroid, dexamethasone. Discs were implanted submuscularly into a well-characterized rat model of the FBR and evaluated for inflammatory response, fibrotic development, and cytokine release. RESULTS: Coated silicone discs exhibited reduced collagen deposition and little to no foreign body giant cells at the host-silicone interface when compared with the silicone-only group. Therapeutic hydrogels demonstrate a significant decrease in cellular infiltration into the coatings over the 2-week time point in contrast to therapeutic-free hydrogel coatings. Cytokine analysis revealed significant differences between therapeutic-free and therapeutic-containing coatings when compared with silicone-only controls. Levels of IL-1ß, IL-6, monocyte chemotactic protein 1, and macrophage inflammatory protein 3α were affected 48 hours after implantation, while differences in IL-18, growth-regulated oncogene/keratinocyte chemoattractant, and macrophage inflammatory protein 3α were observed 1 week after implantation. CONCLUSIONS: By utilizing the host's innate immune response, our engineered hydrogel coatings delivered therapeutic moieties directly to the implant microenvironment, thus delaying the FBR up to 2 weeks.

Tissue Dynamics: Lessons Learned From Sutural Morphogenesis and Cancer Growth.

UNLABELLED: Why are cranial sutures the way they are? How do cancers grow? Merging physics and mathematics with biology, we develop equations describing these complex adaptive systems, to which all biological entities belong, calling them laws of tissue dynamics:Where t is time, E is energy, M is body mass, X is the biological characteristic of interest, C is a constant, a is an exponent.(1) is based on conservation of matter: for any given tissue, materials in must equal to materials out +/- assimilated or degraded. (2) is based on energy conservation. All living systems require energy, without which life becomes impossible. Equation (2) is a power spectrum. OBJECTIVES: This study aimed to introduce the laws of tissue dynamics and to illustrate them using observations from craniofacial and cancer growth. METHODS: We use cranial sutures as a model system to test Equation (1), we also measure the in vitro growth rate of normal murine liver and spleen cells, comparing them to B16F10 melanoma cells. We show the increase in compound growth rate and energetic requirement of malignant versus normal cells as partial proof of Equation (2). RESULTS: The constant width and wavy form of cranial sutures are the inevitable results of repeated iteration from coupling of growth and stress. The compound growth rate of B10F16 melanoma cells exceeds that of normal cells by 1.0 to 1.5%, whereas their glucose uptake is equal to 3.6 billion glucose molecules/cell per minute. SUMMARY: Living things are complex adaptive systems, thus a different way of thinking and investigating, going beyond the current reductive approach, is required.

AAST multicenter prospective analysis of prehospital tourniquet use for extremity trauma.

BACKGROUND: Tourniquet use for extremity hemorrhage control has seen a recent increase in civilian usage. Previous retrospective studies demonstrated that tourniquets improve outcomes for major extremity trauma (MET). No prospective study has been conducted to date. The objective of this study was to evaluate outcomes in MET patients with prehospital tourniquet use. We hypothesized that prehospital tourniquet use in MET decreases the incidence of patients arriving to the trauma center in shock. METHODS: Data were collected prospectively for adult patients with MET at 26 Level I and 3 Level II trauma centers from 2015 to 2020. Limbs with tourniquets applied in the prehospital setting were included in the tourniquet group and limbs without prehospital tourniquets were enrolled in the control group. RESULTS: A total of 1,392 injured limbs were enrolled with 1,130 tourniquets, including 962 prehospital tourniquets. The control group consisted of 262 limbs without prehospital tourniquets and 88 with tourniquets placed upon hospital arrival. Prehospital improvised tourniquets were placed in 42 patients. Tourniquets effectively controlled bleeding in 87.7% of limbs. Tourniquet and control groups were similarly matched for demographics, Injury Severity Score, and prehospital vital signs (p > 0.05). Despite higher limb injury severity, patients in the tourniquet group were less likely to arrive in shock compared with the control group (13.0% vs. 17.4%, p = 0.04). The incidence of limb complications was not significantly higher in the tourniquet group (p > 0.05). CONCLUSION: This study is the first prospective analysis of prehospital tourniquet use for civilian extremity trauma. Prehospital tourniquet application was associated with decreased incidence of arrival in shock without increasing limb complications. We found widespread tourniquet use, high effectiveness, and a low number of improvised tourniquets. This study provides further evidence that tourniquets are being widely and safely adopted to improve outcomes in civilians with MET. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Torso injuries after fall from standing-empiric abdominal or thoracic CT imaging is not indicated.

PURPOSE: Falls from standing (FFS) have become the most common mechanism of injury at many trauma centers. Liberal imaging of low energy trauma has questionable value. We hypothesize that torso trauma intervention is rare in the FFS population, and physical examination sufficiently screens for torso injuries needing intervention. METHODS: We queried our ACS-verified Level 1 trauma center registry for falls from standing from 1/1/14 to 12/31/16. Exclusion criteria were: falls from height, falls associated with penetrating trauma, lack of an abdominal or chest CT, a Glasgow Coma Scale Score (GCS) less than 15, and surgical intervention at another facility prior to arrival at our center. Demographics, historical details, hemodynamics, injuries, injury severity, procedures, initial vital signs, and outcome were recorded. RESULTS: 1,654 patients had a FFS during our study period. 728 had an abdominal or chest CT and a GCS of 15 and comprised the evaluable population. Mean age was 56.5 years. 55.8% were female. The mortality rate was 8%. There were 179 chest injuries in 121 patients, and 54 abdominal injuries in 43 patients. 379 patients had a GCS of 15 and underwent thoracic CT, yet only 11 (3%) underwent intervention. The negative predictive value for physical exam was 100% for chest intervention. 349 patients had a GCS of 15 and abdominal CT, yet only 13 (3.7%) underwent procedural intervention. Abdominal physical exam had a negative predictive value of 99.7% for intervention, but when combined with vital signs, the value was 100%. CONCLUSION: Torso injuries in FFS are rare. Of our study population, 13 abdominal injuries underwent intervention, and 11 chest injuries underwent intervention. Screening patients by physical examination and vital signs is sufficient and safely allows for the use of selective abdominal and chest CT.

Whole body vibration therapy: a novel potential treatment for type 2 diabetes mellitus.

There is a worsening epidemic of obesity and diabetes in the world. Life style interventions including dietary changes and increase in exercise can improve glucose metabolism and health in general. However, standard exercise programs are strenuous, time-consuming, and thus have low long-term compliance issues. We tested the feasibility of using high frequency, low amplitude whole body vibration (WBV) therapy to improve glucose metabolism in young type 2 diabetic (T2DM) mice. We also aimed to investigate the postulated anti-inflammatory and cytoprotective properties of WBV. Male db/db and db/m mice were exposed to high frequency, low-amplitude WBV. Outcome parameters comprised of body weight, hemoglobin A1c (HbA1c) level, as well as interleukin (IL)-17 (a marker of helper T cells), forkhead box P3 (Foxp3; a marker of regulatory T cells), and gammaH2AX (an index of DNA injury) expression. Furthermore, a 24 h metabolic cage study was carried out immediately after the WBV protocol and fluid intake, urine excretion and urine osmolality were determined. WBV did not affect body weight but improved HbA1c levels in db/db mice. Vibrated db/db mice demonstrated less fluid intake and urine excretion but better urinary concentrating ability than their non-vibrated controls. Pro-inflammatory changes were significantly reduced, as indicated by reduced IL-17 but increased Foxp3 expression. WBV reduced gammaH2AX in db/db mice suggestive of cytoprotective effect. However, WBV was largely without significant effects on assessed parameters in db/m mice. Collectively, our findings suggest that daily, short duration WBV may improve glycemic control, polydipsia, polyuria, and urine osmolality in T2DM in association with reduced inflammation. Thus, WBV may be a viable adjunctive treatment strategy in T2DM.

Targeting serum glucocorticoid-regulated kinase-1 in squamous cell carcinoma of the head and neck: a novel modality of local control.

PURPOSE: The inhibition of serum glucocorticoid-regulated kinase-1 (SGK-1) has been found to decrease growth of colon and prostate cancer cells. The purpose of this study is to evaluate the therapeutic effect of SGK-1 inhibition in head and neck squamous cell carcinoma (SCC). EXPERIMENTAL DESIGN: Human head and neck tumors (HTB41/43) were established in athymic mice. Growth rates between mice treated with vehicle (PBS) injection (group 1, n = 5), SGK-1 Inhibitor GSK 650394 (group 2, n = 6), systemic cisplatin (group 3, n = 6), and a combination of SGK-1 Inhibitor and cisplatin (group 4, n = 6) were compared using repeated measures one-way ANOVA with Newman-Keuls Multiple Comparison Test. Tumor cells were subsequently submitted to further analyses. RESULTS: At the end of the experiment mean tumor sizes were 122.33+/-105.86, 76.73+/-36.09, 94.52+/-75.92, and 25.76+/-14.89 mm2 (mean +/- SD) for groups 1 to 4. Groups 2 and 3 showed decreased tumor growth compared to controls (p<0.001). Group 4 displayed even greater growth suppression (p<0.0001). Importantly, group 4 fared better than group 3 (p<0.001). CD44 expression was reduced in group 2 (p<0.05), and to an even greater extent in groups 3 and 4 (p<0.0025). A trend towards reduction of HER 2 expression was noted in group 4. CONCLUSIONS: SGK-1 inhibition suppresses tumor growth, and in combination with systemic cisplatin exceeds the effect of cisplatin alone. Decreased expression of CD44 and HER 2 implies depletion of tumor stem cells, and less tumorigenicity. SGK-1 inhibition represents a potential modality of local control for palliation in advanced cases.