Mortality in patients with respiratory distress syndrome. / Mortalidad en pacientes con síndrome de distress respiratorio.

INTRODUCTION: Mortality in Acute Respiratory Distress Syndrome (ARDS) is decreasing, although its prognosis after hospital discharge and the prognostic accuracy of Berlin's new ARDS stratification are uncertain. METHODS: We did a restrospective analysis of hospital and 6 month mortality of patients with ARDS admitted to the Intensive Care Unit of a Univeristy Hospital in Buenos Aires, between January 2008 and June 2011. ARDS was defined by PaO2/FiO2 lower than 200 mmHg under ventilation with at least 10 cm H2O of PEEP and a FiO2 higher or equal than 0.5. and the presence of bilateral infiltrates in chest radiography, in the absence of cardiogenic acute pulmonary edema, during the first 72 hs of mechanical ventilation. Mortality associated risk factors, the use of rescue therapies and Berlin's stratification for moderate and severe ARDS patients were considered. RESULTS: Ninety eight patients were included; mean age was 59±19 years old, 42,9% had mayor co-morbidities; APACHE II at admission was 22±7; SOFA at day 1 was 8±3. Prone position ventilation was applied in 20,4% and rescue measures in 12,2% (12 patients with nitric oxide and 1 with extracorporeal membrane oxygenation). Hospital and 6 months mortality were 37.7 and 43.8% respectively. After logistic regression analysis, only age, the presence of septic shock at admission, Ppl >30 cmH2O, and major co-morbidities were independently associated with hospital outcome. There was no difference between moderate and severe groups (41,2 and 36,8% respectively; p=0,25). CONCLUSION: In this cohort, including patients with severe hypoxemia and high percentage of mayor co-morbidities, ARDS associated mortality was lower than some previous studies. There was no increase in mortality after hospital discharge. There was no difference in mortality between moderate and severe groups according to Berlin's definition.

[Energy and mass transfer and the productivity of the main ecosystems of Siberia (according to the results of measurements by the method of turbulent pulsations). 2. Carbon exchange and productivity].

Using direct measurements of CO2 fluxes by the method of turbulent pulsations, it was shown that the studied middle-taiga pine forest, raised bog, true steppe, and southern tundra along the Yenisei meridian (approximately 90 degrees E) are stocks of carbon of different capacity in the annual output. The tundra starts to function as a stock of carbon from June; the forest and bog, from May; and the steppe, from the end of April. In the transitional seasons and winter, the ecosystems are a weak source of carbon: the tundra already in September; the forest and bog, from October; and the steppe, from November. The photosynthetic productivity of the forest and steppe ecosys- tems (480-530 g C/(m x year) exceeds 2-2.5 times the productivity ofbogs and tundras (200-220 g C/(m x year). The relationships between the thermal balance structure and CO2 exchange are shown. Possible feedbacks between the carbon exchange between the ecosystems and the atmosphere as a result of climate warming in the region are assessed.

Tanshinone VI inhibits the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.

This study investigated the possible antitumor mechanisms of action of Tanshinone VI, one of the components of Salvia miltiorrhiza Bunge, which is used in traditional Chinese herbal medicine. To this end, the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were evaluated in-vitroin tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells, with, or without the addition of Tanshinone VI (10, 20, 30, or 40 mM) in the culture medium; the effects of Tanshinone VI on angiogenesis was also evaluated with an epithelial cell tube formation assay and its toxicity was evaluated with a colorimetric (MTT) cell viability assay. The results showed that the up-regulation of ICAM-1 and VCAM-1 induced by TNF-alpha was dose-dependently inhibited by Tanshinone VI, with restoration of control levels at the dose of 40 mM; Tanshinone VI also had a remarkable anti-angiogenesis effect, already at the dose of 10 mM, while none of the doses tested had significant effects on cell viability. These results indicate that the antitumor properties of Tanshinone VI can be ascribed to the inhibition of cell adhesion, due to blockage of the up-regulation of cell adhesion molecules, with the consequent inhibition of metastases formation and/or angiogenesis. The lack of toxic effects at the dosage used makes Tanshinone VI a good candidate for its therapeutic use in humans.

[Energy and mass exchange and the productivity of the main ecosystems of Siberia (from eddy covariance measurements). 1. Heat balance structure in the vegetation season].

Direct measurements of heat balance (turbulent heat transfer and evaporation heat consumption) by the method of turbulent pulsations in 1998-2000 and 2002-2004 were used to obtain information on the daily, seasonal, and annual dynamics of energy fluxes and mass transfer between the atmosphere and the typical ecosystems of Siberia (middle-taiga pine forest and raised bog, true four-grass steppe, with the use of data for typical tundra) along the Yenisei meridian (90 degrees E).

Europe-wide reduction in primary productivity caused by the heat and drought in 2003.

Future climate warming is expected to enhance plant growth in temperate ecosystems and to increase carbon sequestration. But although severe regional heatwaves may become more frequent in a changing climate, their impact on terrestrial carbon cycling is unclear. Here we report measurements of ecosystem carbon dioxide fluxes, remotely sensed radiation absorbed by plants, and country-level crop yields taken during the European heatwave in 2003. We use a terrestrial biosphere simulation model to assess continental-scale changes in primary productivity during 2003, and their consequences for the net carbon balance. We estimate a 30 per cent reduction in gross primary productivity over Europe, which resulted in a strong anomalous net source of carbon dioxide (0.5 Pg C yr(-1)) to the atmosphere and reversed the effect of four years of net ecosystem carbon sequestration. Our results suggest that productivity reduction in eastern and western Europe can be explained by rainfall deficit and extreme summer heat, respectively. We also find that ecosystem respiration decreased together with gross primary productivity, rather than accelerating with the temperature rise. Model results, corroborated by historical records of crop yields, suggest that such a reduction in Europe's primary productivity is unprecedented during the last century. An increase in future drought events could turn temperate ecosystems into carbon sources, contributing to positive carbon-climate feedbacks already anticipated in the tropics and at high latitudes.

Dual mobility system. The French solution in elderly patients with intracapsular hip fracture and high risk of dislocation. / Sistema de doble movilidad. La solución francesa en pacientes añosos con fractura intracapsular de cadera y alto riesgo de luxación.

OBJECTIVE: Actually there is a controversy about the treatment of hip fractures on older patients with high risk of dislocation. Our study is focused on report clinico-functional and radiographic results in this population treated with total hip replacement using a dual mobility system after a minimum follow up of 2 years. MATERIALS AND METHODS: In the period from January 2015 to January 2016 patients assisted at the Emergency Unit at the participant hospital were recluted for participation. A total of 137 patients were assisted and 41 fulfilled the inclusion criteria and accepted to participate. All patients received a total hip replacement with a dual mobility system (cemented or uncemented). The patients were evaluated with the Mini-Mental State Examination, walking distance test, preop and postop at 3 and 6 weeks, 3 months, 6 months, one year and subsequent years. Radiographic evaluation was scheduled with clinico-functional review. RESULTS: Forty-one patients included, follow up average 2.4 years (range 2 to 3.2 years). Mean age 85.2 (range 80 to 96 years). Four patients died during follow up due to causes not related to the total hip replacement and the implant was functioning. One case have an infection and was revised in one stage procedure. One case have an infection at 8 months follow-up and was revised in one stage procedure. There were no dislocations. CONCLUSION: The use of dual mobility system in this high dislocation risk population has shown good clinical and functional results, and support the sistematic indication in our services.

Inducing ovulation with hCG improves the fertility of dairy cows during the warm season.

This study was designed to assess the effects of human chorionic gonadotrophin (hCG), given within a timed artificial insemination program, on plasma progesterone concentrations and subsequent fertility in lactating dairy cows during the warm and cold seasons of the year. Cows were treated intramuscularly with GnRH-agonist (Day 0) and PGF(2alpha) (Day 7) followed by either GnRH-agonist (GPG treatment; 60 animals) or hCG (GPH treatment; 60 animals) on Day 9. All cows were fixed-time inseminated (TAI) 16-22h after the end of treatment. To determine plasma progesterone levels, blood was withdrawn from all animals on Days 3, 6, 9, 12 and 15 after TAI. During the warm period, the pregnancy rate recorded at TAI was similar for the GPG and GPH groups (20% vs. 23%) while the cumulative pregnancy rate within 30 days of TAI was lower (P<0.05) for the GPG than the GPH group (36% vs. 63%). No differences were observed during the cold period. During the warm period, embryo losses between Days 28 and 45 after TAI were greater (P<0.05) for the GPG group compared to the GPH group (36% vs. 5%) while again no differences emerged during the cold period. Mean plasma progesterone levels were higher (P<0.05) in the GPH group than GPG group on Days 3, 6 and 9 post-insemination. Our findings indicate that the use of hCG to induce ovulation in a timed artificial insemination protocol increases plasma progesterone levels and improves fertility in dairy cows during the warmer period of the year.

The nonspecificity of focal segmental glomerulosclerosis. The defining characteristics of primary focal glomerulosclerosis, mesangial proliferation, and minimal change.

We performed a detailed clinical review and pathologic analysis of the kidney biopsies of 134 children with nephrotic syndrome or asymptomatic proteinuria. This analysis challenges some of our concepts about the classification of conditions associated with these disorders. The presence of focal segmental sclerotic lesions does not define a unique disorder in childhood. Some children with such lesions will have unaffected glomeruli that are ultrastructurally completely normal. These patients, predominately black adolescents, present either with nephrotic syndrome or asymptomatic proteinuria. We classify this disorder as primary focal segmental glomerulosclerosis (FSGS) and have never found it to recur after transplantation. Most other children with FSGS have 1 of 2 specific glomerulopathies. Those with minimal change have generalized fusion of podocyte foot processes. Those with mesangial proliferation have similar foot process changes combined with mesangial expansion and proliferation and, frequently, thinning of the lamina densa and tubuloreticular inclusions. The presence of segmental lesions in these glomerulopathies appears to be nothing more than a marker of severity. Children with these glomerulopathies are generally younger white children, virtually all of whom have nephrotic syndrome. These disorders have a strong propensity to recur after transplantation. The presence of mesangial labeling of IgM or C1q has no significance in any of these 3 disorders. The classification of disorders associated with nephrotic syndrome or asymptomatic proteinuria must concentrate less on the presence or absence of focal sclerosis and more on the histologic appearance of the rest of the glomeruli.

Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment.

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Human osteoblast response in vitro to platelet-derived growth factor and transforming growth factor-beta delivered from controlled-release polymer rods.

The purpose of this work was (1) to develop extrudable ethylene-vinyl acetate (EVA) copolymer delivery systems capable of sustained release of bioactive proteins and (2) to determine the effect of platelet-derived growth factor (PDGF-BB) and/or transforming growth factor-beta2 (TGF-beta2) on human osteoblast proliferation and differentiation. Human osteoblasts were plated in vitro and proliferation and protein synthesis assayed at 48 and 96 h. EVA-PDGF rods releasing about 34 ng per ml PDGF per day produced a dramatic early increase in osteoblast proliferation and no effect on protein synthesis. EVA-TGF-beta2 rods releasing about 23 ng per ml per day increased protein synthesis but had no effect on proliferation. PDGF and TGF-beta2 together resulted in moderate increases in proliferation and a marked increase in protein synthesis. Morphologically, PDGF-treated cells became confluent as early as 48 h, while TGF-beta2-treated cells formed into nodules. This work shows that (1) it is possible to deliver physiological levels of bioactive proteins from an extrudable EVA delivery system, and (2) bone cell response is dependent on the sequence and timing of delivery. Controlled-release delivery systems which mimic injury-induced healing cascades may be useful in evaluating the role of various molecules in osseous repair.

Influence of surface texture of polymeric sheets on peripheral nerve regeneration in a two-compartment guidance system.

Synthetic guidance channels are useful tools to study the mechanisms underlying peripheral nerve regeneration. In the present study, the lumen of silicone elastomer tubes was divided into two compartments by a polymer strip 10 mm long placed along the tube length. The influence of varying the surface texture of hydrophilic and hydrophobic polymer strips on the morphology of the regenerated neural tissue was analysed. Hydrophilic nitrocellulose (NC) and hydrophobic polyvinylidene fluoride (PVDF) films with smooth (S-NC and S-PVDF) or rough (R-NC, R-PVDF) surface texture were used. Five channels of each type were used to repair transected rat sciatic nerves and analysed after 4 wk. Tissue strips bridged the nerve stumps in all R-NC and R-PVDF tubes, in five of the S-NC and three of the S-PVDF tubes. In R-NC and R-PVDF tubes, bell-shaped tissue adhering to the polymer strip was observed, whereas in S-NC and S-PVDF tubes round, free-floating nerve cables were seen. All the cables contained myelinated and unmyelinated axons and Schwann cells grouped in microfascicles and surrounded by an epineurial layer. For both rough strips, the initial cell layer consisted of macrophages adhering to the polymer surface. The epineurial nerve tissue contacting the rough surface was significantly thinner for PVDF compared with NC strips. No difference in epineurial thickness was observed for nerves facing the silicone tube or for smooth NC and PVDF strips. S-PVDF tubes contained significantly more myelinated axons than S-NC tubes.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrically charged polymeric substrates enhance nerve fibre outgrowth in vitro.

The physical, chemical and electrical properties of synthetic guidance devices are known to influence nerve regeneration in vivo. In the present study, neurons were cultured directly on electrically charged polymer growth substrates to determine if local electrical charges enhance nerve fibre outgrowth in vitro. Piezoelectric polymers such as polyvinylidene fluoride (PVDF) generate transient surface charges under minute mechanical strain. Mouse neuroblastoma (Nb2a) cells were cultured directly on electrically poled (i.e. piezoelectric) and unpoled (i.e. nonpiezoelectric) PVDF substrates in serum-free and serum-containing media. Nerve fibre outgrowth was analysed 24, 48, 72 and 96 h after plating. Piezoelectric PVDF substrates generated 2-3 mV at 1200 Hz when placed on standard incubator shelves and unpoled PVDF substrates showed no output. Nb2a cells grown on piezoelectric substrates exhibited significantly greater levels of process outgrowth and neurite lengths at all time periods for both media conditions. Detailed surface characterization of PVDF substrates using electron spectroscopy for chemical analysis (ESCA) and a comprehensive wettability profile revealed that poled and unpoled PVDF was chemically indistinguishable and showed similar surface wettabilities and adhesive properties. Therefore, we conclude that enhanced process outgrowth was induced by the film's piezoelectric output, making poled PVDF a unique biomaterial for which cell/polymer interactions are mediated predominantly through bulk electrical properties rather than surface properties.

Improved nerve regeneration through piezoelectric vinylidenefluoride-trifluoroethylene copolymer guidance channels.

Piezoelectric materials generating electrical charges in response to mechanical strain may be used to stimulate axonal regeneration following nerve injury. Tubular nerve guidance channels were extruded from a vinylidenefluoride-trifluoroethylene copolymer using a melt-extrusion process. Unlike vinylidenefluoride homopolymer, the copolymer does not need mechanical stretching to achieve a dipole-containing crystal structure, enabling the fabrication of complex piezoelectric devices. Selected tubes were rendered piezoelectric in a high voltage corona poling apparatus. Crystal structure changes induced by poling were evaluated with differential scanning calorimetry. In contrast to unpoled samples, poled ones displayed a sharp endothermic peak and a greater heat of transition at the Curie temperature, indicative of an increase in crystal order and size. The piezoelectric output of poled tubes was characterized using a laser-monitored deflection system interfaced with a charge amplifier and oscilloscope. Poled tubes generated significant voltages in response to slight mechanical deformations. The magnitude of electrical output was independent of the poling polarity. Unpoled tubes showed no electrical output. Positive, negative and unpoled vinylidenefluoride-trifluoroethylene copolymer tubes were used to repair a 10 mm gap in transected sciatic nerves of adult rats. Nerves regenerated in positively poled channels had a significantly greater number of myelinated axons than those regenerated in unpoled channels 4 wk post-implantation. Negatively poled channels contained an intermediate number of myelinated axons. We concluded that piezoelectrically active vinylidenefluoride-trifluoroethylene copolymer tubes significantly enhance nerve regeneration as compared to chemically identical, unpoled tubes and that the polarity of the corona poling procedure used to fabricate piezoelectric materials may play a role in determining biological responses.

Controlled release of platelet-derived growth factor using ethylene vinyl acetate copolymer (EVAc) coated on stainless-steel wires.

Controlled delivery of bioactive molecules to modulate or control biological processes has a number of clinical applications. The present study reports a delivery system which was designed to deliver growth factors locally to a fracture site. Ethylene vinyl acetate copolymer (EVAc), bovine serum albumin (BSA) and platelet-derived growth factor (PDGF-BB) were combined and coated onto a stainless-steel Kirschner wire (K-wire). A K-wire can be used as an intramedullary nail in small animal fractures, such as the rat. PDGF-BB stimulates thymidine uptake in human bone cell cultures when released from the K-wire delivery system. BSA release was modified by providing a final coating on the K-wire of 10% pure EVAc at the end of the fabrication. Electron microscopic examination of the surface of the rods revealed different surface pores on the K-wires coated with pure EVAc. Differences in porosity and tortuosity may account, in part, for the different release kinetics observed.

RGD-coated titanium implants stimulate increased bone formation in vivo.

Numerous studies have demonstrated that peptide modified surfaces influence short- and long-term cell responses such as attachment, shape and function in vitro. These responses are mediated via cell receptors known as integrins which bind specifically to short peptide sequences from larger proteins. Integrins transduce information to the nucleus through several cytoplasmic signalling pathways. Little is known, however, about the ability of peptide-coated surfaces to influence cell responses in vivo. The present study was designed to evaluate the quality and quantity of the new bone formed in response to titanium rods surface-coated with the peptide sequence Arg-Gly-Asp-Cys (RGDC) using gold-thiol chemistry and implanted in rat femurs. Histomorphometric analysis of cross-sections perpendicular to the implant long axis showed a significantly thicker shell of new bone formed around RGD-modified versus plain implants at 2 weeks (26.2 +/- 1.9 vs. 20.5 +/- 2.9 microm; P < 0.01). A significant increase in bone thickness for RGD implants was also observed at 4 weeks while bone surrounding controls did not change significantly in thickness (32.7 +/- 4.6 vs. 22.6 +/- 4.0 microm; P < 0.02). Mechanical pull-out testing conducted at 4 weeks revealed the average interfacial shear strength of peptide modified rods was 38% greater than control rods although this difference was not statistically significant. These pilot data suggest that an RGDC peptide coating may enhance titanium rod osseointegration in the rat femur. Long-term studies and evaluation of other peptides in larger animal models are warranted.

Growth hormone bioactivity and levels of growth hormone, growth hormone-binding protein, insulinlike growth factor I, and insulinlike growth factor-binding proteins in premature and full-term newborns during the first month of life.

OBJECTIVE: To assess the pattern of growth hormone bioactivity (GH-BIO) and the levels of GH-binding protein (GH-BP), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding proteins (IGFBPs) in the first month of life in premature and full-term (FT) newborns. PATIENTS AND METHODS: Serum samples were collected from 9 premature newborns who were small for gestational age, 18 premature newborns who were of appropriate size for gestational age, and 20 FT newborns on the 4th and 30th days of life to evaluate the GH-BIO using the Nb2 cell bioassay, the GH levels using a radio-immunoassay (GH-RIA), and the levels of GH-BP, IGF-I and IGFBPs. RESULTS: On day 4, the GH-RIA and GH-BIO values were increased in all newborns (P < .05) compared with values in the prepubertal control subjects. The GH-BP levels were low in all newborns, with the lowest values (P < .05) found in the premature newborns and positively correlated with gestational age (P < .001). The IGF-I levels were also low, with lower values (than those found in the FT newborns) (P < .005) found in the premature group and positively correlated with the GH-BP levels (P < .001) and gestational age (P < .001). The levels of IGFBP-1 and IGFBP-2 were high, with higher values found in the premature newborns than in the FT newborns (P < .05) and negatively correlated with gestational age (P < .005). The IGFBP-3 level was lower in the premature (P < .05) than in the FT newborns and positively correlated with gestational age (P < .005). During the first month of life, the GH-RIA and GH-BIO values were significantly decreased in all newborns (P < .001), while the IGF-I level was increased in the premature newborns (P < .005). The GH-BP levels were increased only in the FT newborns (P < .001). CONCLUSIONS: The elevated bioactive GH level seen in the first few days of life seemed to be attributable to a low IGF-I level secondary to a decreased number and/or function of the GH receptors. The decrease in the serum GH level observed thereafter seemed to be secondary to an increase in the IGF-I level in the premature newborns; however, other factors may have been involved in the FT newborns in whom no increase in the IGF-I level was observed.

Postnatal variations of growth hormone bioactivity and of growth hormone-dependent factors.

OBJECTIVE: To evaluate whether the low insulinlike growth factor I (IGF-I) levels that are observed in the neonate depend on the biological inactivity of the molecular forms of growth hormone (GH) or on the immaturity of the hepatic GH receptors during the early postnatal period. MATERIALS AND METHODS: Serum samples were collected from 60 normal full-term neonates on day 5 and at 1 and 4 months of age to evaluate the GH concentrations by using both an immunofluorometric assay and Nb2 cell bioassay, as well as the GH-binding protein, IGF-I, and IGF-binding protein 3 values by radioimmunoassay. RESULTS: Five-day-old neonates showed significantly higher (P < .001) mean +/- SEM GH levels that were measured by using the immunofluorometric assay (27.22 +/- 1.62 micrograms/L) and Nb2 cell bioassay (3.56 +/- 0.14 U/mL) compared with those levels in 11 prepubertal children who were studied as control subjects (1.26 +/- 0.28 micrograms/L and 0.74 +/- 0.08 U/mL, respectively). At 1 and 4 months of age, GH values that were measured by using both the immunofluorometric assay (9.15 +/- 0.89 and 2.58 +/- 0.32 micrograms/L, respectively) and Nb2 cell bioassay (2.52 +/- 0.11 and 1.71 +/- 0.15 U/mL, respectively) were decreased significantly (P < .001). In 5-day-old neonates, we observed significantly lower (P < .001) serum GH-binding protein (9.73% +/- 0.42%), IGF-I (67.63 +/- 5.20 ng/mL), and IGF-binding protein 3 (1.46 +/- 0.17 mg/L) concentrations compared with those in the prepubertal children (30.74% +/- 2.01%, 210 +/- 25 ng/mL, and 3.08 +/- 0.22 mg/L, respectively). At 1 month of age, serum GH-binding protein (16.00% +/- 0.70%) and IGF-binding protein 3 (2.96 +/- 0.30 mg/L) values were increased significantly (P < .001), while IGF-I levels (72.55 +/- 7.6 ng/mL, P = .09) were not increased. Serum IGF-I values were increased significantly (P < .005) at 4 months of age (97.94 +/- 9.68 ng/mL). CONCLUSION: The interaction of bioactive molecular forms of GH with the increased hepatic GH receptors induces the rise in postnatal IGF-I levels in early infancy.

The morphology of regenerating peripheral nerves is modulated by the surface microgeometry of polymeric guidance channels.

The present study was designed to evaluate the influence of synthetic guidance channel surface microgeometry on morphological patterns of neural regeneration. Tubes with smooth (S), rough (R), or alternating smooth-rough (S/R) or rough-smooth (R/S) inner surfaces but with identical chemical composition and permeability characteristics were used to bridge a 4-mm nerve gap in a transected mouse sciatic nerve. Animals received S and R channels for 1, 2 and 4 weeks and both S/R and R/S channels for 2 and 4 weeks. At 1 week, the S tubes contained a longitudinally oriented fibrin matrix not contacting the channel's smooth inner wall, whereas R tubes featured an unorganized fibrin matrix which, together with fibroblasts and macrophages, had invaded the channel's rough trabecular network. After 4 weeks, S tubes contained discrete, free-floating nerve cables with numerous myelinated and unmyelinated axons surrounded by a thin, continuous epineurial-like layer, whereas R tubes were completely filled with a loose connective tissue stroma with only a few axons. In combined S/R or R/S channels, the general morphological patterns in individual S or R segments were similar to those observed in pure S or R channels, regardless of whether the tube segment was positioned at the proximal or distal nerve end. Proximal smooth channel segments contained discrete cables which abruptly fanned out to completely fill the lumen in distal rough segments. The opposite pattern was observed with proximal rough and distal smooth segments. At 4 weeks, myelinated axons were observed along the entire length of S/R and R/S tubes. These results suggest that the surface microgeometry of guidance channels influences the outcome of peripheral nerve regeneration, potentially by affecting the early arrangement of the fibrin matrix and/or inducing different cellular responses.