Nitro-Oleic Acid (NO2-OA) Release Enhances Regional Angiogenesis in a Rat Abdominal Wall Defect Model.

Ventral hernia is often addressed surgically by the placement of prosthetic materials, either synthetic or from allogeneic and xenogeneic biologic sources. Despite advances in surgical approaches and device design, a number of postsurgical limitations remain, including hernia recurrence, mesh encapsulation, and reduced vascularity of the implanted volume. The in situ controlled release of angiogenic factors from a scaffold facilitating abdominal wall repair might address some of these issues associated with suboptimal tissue reconstruction. Furthermore, a biocomposite material that combines the favorable mechanical properties achievable with synthetic materials and the bioactivity associated with xenogeneic tissue sources would be desirable. In this report, an abdominal wall repair scaffold has been designed based on a microfibrous, elastomeric poly(ester carbonate)urethane urea matrix integrated with a hydrogel derived from decellularized porcine dermis (extracellular matrix [ECM] gel) and poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nitro-oleic acid (NO2-OA). NO2-OA is an electrophilic fatty acid nitro-alkene derivative that, under hypoxic conditions, induces angiogenesis. This scaffold was utilized to repair a rat abdominal wall partial thickness defect, hypothesizing that the nitro-fatty acid release would facilitate increased angiogenesis at the 8-week endpoint. The quantification of neovascularization was conducted by novel methodologies to assess vessel morphology and spatial distribution. The repaired abdominal wall defects were evaluated by histopathologic methods, including quantification of the foreign body response and cellular ingrowth. The results showed that NO2-OA release was associated with significantly improved regional angiogenesis. The combined biohybrid scaffold and NO2-OA-controlled release strategy also reduced scaffold encapsulation, increased wall thickness, and enhanced cellular infiltration. More broadly, the three components of the composite scaffold design (ECM gel, polymeric fibers, and PLGA microparticles) enable the tuning of performance characteristics, including scaffold bioactivity, degradation, mechanics, and drug release profile, all decisive factors to better address current limitations in abdominal wall repair or other soft tissue augmentation procedures.

In vivo monitoring of structural and mechanical changes of tissue scaffolds by multi-modality imaging.

Degradable tissue scaffolds are implanted to serve a mechanical role while healing processes occur and putatively assume the physiological load as the scaffold degrades. Mechanical failure during this period can be unpredictable as monitoring of structural degradation and mechanical strength changes at the implant site is not readily achieved in vivo, and non-invasively. To address this need, a multi-modality approach using ultrasound shear wave imaging (USWI) and photoacoustic imaging (PAI) for both mechanical and structural assessment in vivo was demonstrated with degradable poly(ester urethane)urea (PEUU) and polydioxanone (PDO) scaffolds. The fibrous scaffolds were fabricated with wet electrospinning, dyed with indocyanine green (ICG) for optical contrast in PAI, and implanted in the abdominal wall of 36 rats. The scaffolds were monitored monthly using USWI and PAI and were extracted at 0, 4, 8 and 12 wk for mechanical and histological assessment. The change in shear modulus of the constructs in vivo obtained by USWI correlated with the change in average Young's modulus of the constructs ex vivo obtained by compression measurements. The PEUU and PDO scaffolds exhibited distinctly different degradation rates and average PAI signal intensity. The distribution of PAI signal intensity also corresponded well to the remaining scaffolds as seen in explant histology. This evidence using a small animal abdominal wall repair model demonstrates that multi-modality imaging of USWI and PAI may allow tissue engineers to noninvasively evaluate concurrent mechanical stiffness and structural changes of tissue constructs in vivo for a variety of applications.

[Effect of noise on the auditory system and the intelligence development of premature infants treated in the neonatal intensive care unit].

OBJECTIVE: High noise levels (>70 dB) in the neonatal intensive care unit (NICU) are common in some primary hospitals. This study aimed to investigate the noise in the NICU on auditory system and intelligence development in premature infants. METHODS: One hundred premature infants with respiratory distress syndrome who needed mechanical ventilation therapy were randomly divided into observation and control groups according to the use of earmuffs. The duration of mechanical ventilation therapy lasted for 2 to 15 days in the two groups. After weaning from mechanical ventilator, the auditory brainstem response, cranial B-ultrasonography, and the intelligence development assessment were performed. RESULTS: The percentage of total (23% vs 47%) and mild hearing loss (15% vs 35%) in the observation group was significantly lower than that in the control group (p<0.05) 2 to 3 days after weaning from mechanical ventilator. The incidence of periventricular hemorrhage intraventricular hemorrhage (PVH-IVH) or periventricular leukomalacia (PVL) in the observation group was significantly lower than that in the control group (21% vs 42%; p<0.05). The intelligence development assessment performed in the first 6 and 12 months of life showed that the mental development index and the psychomotor development index in the observation group were much higher than those in the control group (p<0.05). CONCLUSIONS: The noise in the NICU can result in mild hearing loss and retardation of intelligence development and increase the incidence of PVH-IVH and PVL in premature infants. The use of earmuff may reduce the adverse events.

Sonic hedgehog cascade is required for penile postnatal morphogenesis, differentiation, and adult homeostasis.

The penis is unique in that it undergoes morphogenesis and differentiation primarily in the postnatal period. For complex structures such as the penis to be made from undifferentiated precursor cells, proliferation, differentiation, and patterning are required. This process involves coordinated activity of multiple signals. Sonic hedgehog (Shh) forms part of a regulatory cascade that is essential for growth and morphogenesis of many tissues. It is hypothesized that the penis utilizes regulatory mechanisms similar to those of the limb and accessory sex organs to pattern penile postnatal morphogenesis and differentiation and that the Shh cascade is critical to this process. To test this hypothesis, Shh, BMP-4, Ptc, and Hoxa-10 localization and function were examined in Sprague-Dawley rat penes by means of quantitative reverse transcription polymerase chain reaction, in situ hybridization, immunohistochemistry, and Western blotting. These genes were expressed in the penis during postnatal morphogenesis in a spatially and temporally restricted manner in adjacent layers of the corpora cavernosal sinusoids. The function of Shh and BMP-4 is to establish and maintain corpora cavernosal sinusoids. The data suggest that Ptc and Hoxa-10 are also important in penile morphogenesis. The continuing function of Shh and targets of its signaling in maintaining penile homeostasis in the adult is significant because disruption of Shh signaling affects erectile function. This is the first report that demonstrates the significant role that Shh plays in establishing and maintaining penile homeostasis and how this relates to erectile function. These studies provide valuable insight that may be applied to improve treatment options for erectile dysfunction.