Novel treatment of intracerebral hemorrhage with mechanical tissue resuscitation.

OBJECTIVE: The previous laboratory and clinical experience of the authors had demonstrated that application of controlled subatmospheric pressure directly to injured soft tissue can result in increased survival of compromised tissues. Mechanical tissue resuscitation (MTR) is a new concept evolving from these discoveries. The authors' recent studies have demonstrated that traumatic brain injury tissue can also be salvaged. The aim of this study was to examine the effects of MTR application to injuries from intracerebral hemorrhages (ICHs) in a swine model. METHODS: The ICHs in swine were simulated by infusion of autologous artery blood into the right frontal lobe. A specially designed silicone manifold device was introduced directly into the hematoma. Continuous negative pressure at -50 mm Hg was applied through this device. T2- and T2*-weighted MRI, histological H&E staining, and immunostaining were examined. RESULTS: After 1 week of treatment, MTR significantly decreased gross hematoma volume by more than 60%, from 472.62 ± 230.19 mm3 in the nontreated group to 171.25 ± 75.38 mm3 in the MTR-treated group (p < 0.05). Total hypointense volumes measured on T2*-weighted MR images decreased from 791.99 ± 360.47 mm3 in the nontreated group to 371.16 ± 105.75 mm3 in the MTR-treated group (p < 0.05). The hyperintense area on the T2-weighted MR image decreased significantly from 2656.23 ± 426.26 mm3 in the nontreated group to 1816.66 ± 525.26 mm3 in the MTR-treated group (p < 0.05). When ICHs were treated with MTR for 2 weeks, the gross hematomas were reduced by 94%, from 112.23 ± 66.21 mm3 in the nontreated group to 6.12 ± 10.99 mm3 in the MTR-treated group (p = 0.003). MTR significantly decreased the total necrotic tissue volume in H&E staining from 120.42 ± 48.35 mm3 in the nontreated group to 60.94 ± 38.99 mm3 in the MTR-treated group (p < 0.05). The total hypointense volumes on T2*-weighted MR images were significantly reduced, from 385.54 ± 93.85 mm3 in the nontreated group to 220.54 ± 104.28 mm3 in the MTR-treated group (p < 0.05), while their mean T2 hyperintense volume decreased significantly from 2192.83 ± 728.27 mm3 in the nontreated group to 1366.97 ± 463.36 mm3 in the MTR-treated group (p < 0.05). Histology revealed that the capillary diameter in the reactive tissue rim adjacent to the hematoma increased in both the 1- and 2-week MTR-treated groups. Both von Willebrand factor and CD31 signals were detectable in endothelial cells within the hematoma cavity of both MTR-treated groups. CONCLUSIONS: This study demonstrates that local continuous application of controlled subatmospheric pressure to an ICH can safely remove more than half of a clot in 1 week and more than 90% in 2 weeks.

Attenuated tissue damage with Mechanical Tissue Resuscitation in a pig model of spinal cord injury.

Our previous studies on the treatment of spinal cord injuries with Mechanical Tissue Resuscitation (MTR) in rats have demonstrated that it can significantly improve the locomotor recovery and BBB scores. MTR treatment also reduced fluid accumulations by T2-imaging and improved the mean neural fiber number and fiber length in injured sites by fiber tractography. Myelin volume was also significantly preserved by MTR treatment. For further clinical application, a large animal model is necessary to assess this treatment. This study examined the effects of application of MTR on traumatic spinal cord injury in a swine model. Traumatic spinal cord contusion injuries (SCI) in swine were created by controlled pneumatic impact device. Negative pressure at -75 mm Hg was continuously applied to the injured site through open cell silicone manifold for 7 days. In vivo MR imaging for T2 and GRE analysis employed a 3T machine, while a 7T machine was employed for diffusion tensor imaging (DTI) and fiber tractography. Histological HE and Luxol fast blue staining were examined. MTR significantly reduced the mean injured volumes over 46% by T2-imaging in the injured sites from 477.34±146.31 mm3 in non-treated group to 255.99±70.28 mm3 in MTR treated group (P<0.01). It also reduced fluid accumulations by relative T2 signal density in the epicenter of the SCI from 1.62±0.27 in non-treated group to 1.22±0.10 in the MTR treated group (P<0.05). The mean injured tissue volume measured by H&E staining was 303.71±78.21 mm3 in the non-treated group and decreased significantly to 162.16±33.0 mm3 in the MTR treated group (P<0.01). The myelin fiber bundles stained by Luxol blue were preserved much more in the MTR treated group (90±29.71 mm3) than in the non-treated group (33.68±24.99 mm3, P<0.01). The fractional anisotropy (FA) values processed by DTI analysis are increased from 0.203±0.027 in the untreated group to 0.238±0.029 in MTR treatment group (P<0.05). Fiber tractography showings the mean fiber numbers across the impacted area were increased over 112% from 327.0±99.74 in the non-treated group to 694.83±297.86 in the MTR treated group (P<0.05). These results indicates local application of MTR for seven days to spinal cord injury in a swine model decreased tissue injury, reduced tissue edema and preserved more myelin fibers as well as nerve fibers in the injured spinal cord. Keywords: Mechanical tissue resuscitation, Negative pressure treatment, Spinal cord injury, Diffusion tensor imaging, Nerve fiber tractography.

Age-dependent changes in brain hydration and synaptic plasticity.

Aging in humans and animals is associated with gradual and variable changes in some cognitive functions, but what causes them and explains individual variations remains unclear. Hydration decreases with aging but whether dehydration contributes to cognitive dysfunction is not known. The brain hydration of aging mice was determined by colloidosmotic-pressure titration. Dehydration increased with age from ∼76 mmHg at 6 weeks to ∼105 mmHg at 40 weeks, or a progressive ∼10 percent loss of brain water but seemed to level off afterward. When we adjusted dehydration in hippocampal slices of <8-week-old mice to the levels seen in mice 40 weeks and older, their basal synaptic responses were amplified at all stimulus voltages tested, but induction of late-phase long-term potentiation was impaired. Our results document progressive brain dehydration with age in inbred mice to levels at which in vitro synaptic plasticity appears dysregulated. They also suggest that dehydration contributes to some of the changes in synaptic plasticity observed with aging, possibly due to adjustments in neuronal excitation mechanisms.

Local fluid transfer regulation in heart extracellular matrix

The interstitial myocardial matrix is a complex and dynamic structure that adapts to local fluctuations in pressure and actively contributes to the heart's fluid exchange and hydration. However, classical physiologic models tend to treat it as a passive conduit for water and solute, perhaps because local interstitial regulatory mechanisms are not easily accessible to experiment in vivo. Here, we examined the interstitial contribution to the fluid-driving pressure ex vivo. Interstitial hydration potentials were determined from influx/efflux rates measured in explants from healthy and ischemia-reperfusion-injured pigs during colloid osmotic pressure titrations. Adaptive responses were further explored by isolating myocardial fibroblasts and measuring their contractile responses to water activity changes in vitro. Results show hydration potentials between 5 and 60 mmHg in healthy myocardia and shifts in excess of 200 mmHg in edematous myocardia after ischemia-reperfusion injury. Further, rates of fluid transfer were temperature-dependent, and in collagen gel contraction assays, myocardial fibroblasts tended to preserve the micro-environment's hydration volume by slowing fluid efflux rates at pressures above 40 mmHg. Our studies quantify components of the fluid-driving forces in the heart interstitium that the classical Starling's equation does not explicitly consider. Measured hydration potentials in healthy myocardia and shifts with edema are larger than predicted from the known values of hydrostatic and colloid osmotic interstitial fluid pressures. Together with fibroblast responses in vitro, they are consistent with regulatory mechanisms that add local biological controls to classic fluid-balance models (AU)

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Local fluid transfer regulation in heart extracellular matrix.

The interstitial myocardial matrix is a complex and dynamic structure that adapts to local fluctuations in pressure and actively contributes to the heart's fluid exchange and hydration. However, classical physiologic models tend to treat it as a passive conduit for water and solute, perhaps because local interstitial regulatory mechanisms are not easily accessible to experiment in vivo. Here, we examined the interstitial contribution to the fluid-driving pressure ex vivo. Interstitial hydration potentials were determined from influx/efflux rates measured in explants from healthy and ischemia-reperfusion-injured pigs during colloid osmotic pressure titrations. Adaptive responses were further explored by isolating myocardial fibroblasts and measuring their contractile responses to water activity changes in vitro. Results show hydration potentials between 5 and 60 mmHg in healthy myocardia and shifts in excess of 200 mmHg in edematous myocardia after ischemia-reperfusion injury. Further, rates of fluid transfer were temperature-dependent, and in collagen gel contraction assays, myocardial fibroblasts tended to preserve the micro-environment's hydration volume by slowing fluid efflux rates at pressures above 40 mmHg. Our studies quantify components of the fluid-driving forces in the heart interstitium that the classical Starling's equation does not explicitly consider. Measured hydration potentials in healthy myocardia and shifts with edema are larger than predicted from the known values of hydrostatic and colloid osmotic interstitial fluid pressures. Together with fibroblast responses in vitro, they are consistent with regulatory mechanisms that add local biological controls to classic fluid-balance models.

Structural and mechanical characterization of bioresorbable, elastomeric nanocomposites from poly(glycerol sebacate)/nanohydroxyapatite for tissue transport applications.

Poly(glycerol sebacate) (PGS)/nanohydroxyapatite (nHA) composites were assessed to develop new materials for closure via tissue transport for nonhealing defects (e.g., cleft palate and large skin wounds). The elastic shape memory polymer, PGS, was reinforced with nHA at 3 and 5% loading to increase the mechanical properties compared with the undoped PGS. Differential scanning calorimetry (DSC) was utilized to identify a glass transition temperature (Tg ) of -25°C. X-ray diffraction demonstrated a reduction in the amorphous nature of the material. The Fourier transform infrared photoacoustic spectral (FTIR-PAS) data showed decreased CO bonding and increased hydrogen bonding with increased nHA incorporation. Composites exhibited Young's moduli in the range of 0.25-0.5 MPa and tensile strength of 1.5-3 N. No significant difference in extension to break (∼50 mm) with addition of nHA was observed. The elastic modulus significantly increased for 5% PGS/nHA compared to 0 and 3% PGS/nHA and tensile strength significantly increased for 3% PGS/nHA compared to 0 and 5% PGS/nHA. Degradation of 5% nHA/PGS significantly increased during the second week compared to PGS 0 and 3% PGS/nHA. The accelerated degradation for 5% PGS/nHA coupled with decreased flexibility and tensile strength implies an interruption in crosslinking. By maintaining flexibility and extension while increasing tensile strength, the 3% PGS/nHA doped satisfied the force range desired for closure of soft tissue defects. Based on this work, PGS with 3% nHA shape memory polymers should serve as a good candidate for closure of nonhealing soft tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1366-1373, 2016.

Ameliorating Spinal Cord Injury in an Animal Model With Mechanical Tissue Resuscitation.

BACKGROUND: Traumatic spinal cord injury (SCI) is a major worldwide cause of mortality and disability with limited treatment options. Previous research applying controlled negative pressure to traumatic brain injury in rat and swine models resulted in smaller injuries and more rapid recovery. OBJECTIVE: To examine the effects of the application of a controlled vacuum (mechanical tissue resuscitation [MTR]) to SCI in a rat model under several magnitudes of vacuum. METHODS: Controlled contusion SCIs were created in rats. Vacuums of -50 and -75 mm Hg were compared. Analysis included open-field locomotor performance, magnetic resonance imaging (in vivo T2, ex vivo diffusion tensor imaging and fiber tractography), and histological assessments. RESULTS: MTR treatment significantly improved the locomotor recovery from a Basso, Beattie, and Bresnahan score of 7.8 ± 1.9 to 11.4 ± 1.2 and 10.7 ± 1.9 at -50- and -75-mm Hg pressures, respectively, 4 weeks after injury. Both pressures also reduced fluid accumulations > 10% by T2-imaging in SCI sites. The mean fiber number and mean fiber length were greater across injured sites after MTR treatment, especially with treatment with -50 mm Hg. Myelin volume was increased significantly by 60% in the group treated with -50 mm Hg. CONCLUSION: MTR of SCI in a rat model is effective in reducing edema in the injured cord, preserving myelin survival, and improving the rate and quantity of functional recovery. ABBREVIATIONS: BBB, Basso, Beattie, and BresnahanDTI, diffusion tensor imagingFA, fractional anisotropyMTR, mechanical tissue resuscitationMTR50, mechanical tissue resuscitation with 50-mm Hg subatmospheric pressureMTR75, mechanical tissue resuscitation with 75-mm Hg subatmospheric pressureROI, region of interestSCI, spinal cord injury.

Mechanical tissue resuscitation (MTR): a nonpharmacological approach to treatment of acute myocardial infarction.

BACKGROUND AND AIM: Myocardial ischemia-reperfusion injury is known to trigger an inflammatory response involving edema, apoptosis, and neutrophil activation/accumulation. Recently, mechanical tissue resuscitation (MTR) was described as a potent cardioprotective strategy for reduction of myocardial ischemia-reperfusion injury. Here, we further describe the protective actions of MTR and begin to define its therapeutic window. METHODS: A left ventricular, free-wall ischemic area was created in anesthetized swine for 85 minutes and then reperfused for three hours. Animals were randomized to two groups: (1) untreated controls (Control) and (2) application of MTR that was delayed 90 minutes after the initiation of reperfusion (D90). Hemodynamics and regional myocardial blood flow were assessed at multiple time points. Infarct size and neutrophil accumulation were assessed following the reperfusion period. In separate cohorts, the effect of MTR on myocardial interstitial water (MRI imaging) and blood flow was examined. RESULTS: Both groups had similar areas at risk (AAR), hemodynamics, and arterial blood gas values. MTR, even when delayed 90 minutes into reperfusion (D90, 29.2 ± 5.0% of AAR), reduced infarct size significantly compared to Controls (51.9 ± 2.7%, p = 0.006). This protection was associated with a 33% decrease in neutrophil accumulation (p = 0.047). Improvements in blood flow and interstitial water were also observed. Moreover, we demonstrated that the therapeutic window for MTR lasts for at least 90 minutes following reperfusion. CONCLUSIONS: This study confirms our previous observations that MTR is an effective therapeutic approach to reducing reperfusion injury with a clinically useful treatment window.

The Use of Brainlab Navigation in Le Fort III Osteotomy.

Le Fort III osteotomy is commonly used in the surgical correction of midface hypoplasia, specifically in patients with syndromic craniosynostosis. These osteotomies can be associated with significant complications, which are often the result of incomplete or inaccurate osteotomies. Brainlab, a technology first developed for neurosurgery, has been applied to numerous surgical subspecialties. The aim of this study was to report our initial experience using the Brainlab VectorVision2 and Brainlab Curve (Brainlab, Westchester, IL) as an intraoperative guidance system for osteotomy placement during Le Fort III advancement. Three pediatric patients with syndromic craniosynostosis and midface hypoplasia scheduled to undergo Le Fort III advancement were scanned preoperatively with 0.6-mm computed tomography cuts, which were then uploaded to the Brainlab system. All surgeries commenced with rigid fixation of the Brainlab registration device to the patient's skull. The navigation system was used intraoperatively to accurately determine osteotomy sites and trajectories. External distractors were placed without complication. Mean length of surgery was 331 minutes, and mean estimated blood loss was 500 mL. No transfusion was required with a mean postoperative hemoglobin of 8.3 g/dL. The application of Brainlab technology to Le Fort III advancement proved useful in establishing precise osteotomy lines and trajectories. Looking forward, this technology could be applied to a minimal dissection technique in order to avoid extensive blood loss. Further study would be needed to determine possible benefits such as reduced complications or operative time when using an intraoperative navigation system for image-guided osteotomy placement during Le Fort III advancement.

Novel nanofiber-based material for endovascular scaffolds.

Conventional collagen-based heart valves eventually fail because of insufficient replacement of graft material by host tissue. In this study, type I collagen was blended with silk fibroin and the synthetic elastic polymer poly (glycerol-sebacate) (PGS) in varying proportions to create multifunctional electrospun nanofibrous materials tailored for use as endovascular scaffolds such as heart valve replacement. Depending on the blended material the elastic moduli ranged from 2.3 to 5.0 Mpa; tensile stresses ranged from 0.8 to 1.5 Mpa; and strains ranged from 30% to 70%. Electrospun materials with a weight ratio of 4.5:4.5:1 (collagen, fibroin, and PGS) (termed PFC mats) were the most similar to native heart valves. In vitro degradation of PFC mats was 0.01% per week. Endothelial cells adhered to, proliferated, and formed cell-cell junctions on PFC mats. Compared with collagen hydrogels and electrospun collagen mats respectively 220-290% less platelet adhesion was observed for PFC mats. The study demonstrates that PFC material has superior mechanical properties, low degradation, and reduced thrombogenic potential and suggests that further investigation of this biomaterial for cardiovascular applications is warranted.

Eradicating group A streptococcus bacteria and biofilms using functionalised multi-wall carbon nanotubes.

PURPOSE: The aim of this study was to demonstrate that multi-wall carbon nanotubes can be functionalised with antibodies to group A streptoccocus (GAS) for targeted photothermal ablation of planktonic and biofilm residing bacteria. MATERIALS AND METHODS: Antibodies for GAS were covalently attached to carboxylated multi-wall carbon nanotubes and incubated with either planktonic or biofilm GAS. Bacterium was then exposed to 1.3 W/cm(2) of 800 nm light for 10-120 s, and then serially diluted onto agar plates from which the number of colony forming units was determined. Photothermal ablation of GAS on the surface of full thickness ex vivo porcine skin and histological sectioning were done to examine damage in adjacent tissue. RESULTS: Approximately 14% of the GAS antibody-functionalised nanotubes attached to the bacterium, and this amount was found to be capable of inducing photothermal ablation of GAS upon exposure to 1.3 W/cm(2) of 800 nm light. Cell viability was not decreased upon exposure to nanotubes or infrared light alone. Compared to carboxylated multi-wall carbon nanotubes, antibody-labelled nanotubes enhanced killing in both planktonic and biofilm GAS in conjunction with infrared light. Analysis of GAS photothermally ablated in direct contact with ex vivo porcine skin shows that heat sufficient for killing GAS remains localised and does not cause collateral damage in tissue adjacent to the treated area. CONCLUSIONS: The results of this study support the premise that carbon nanotubes may be effectively utilised as highly localised photothermal agents with the potential for translation into the clinical treatment of bacterial infections of soft tissue.

Latest trends in minimally invasive synostosis surgery: a review.

PURPOSE OF REVIEW: To present the current surgical options for minimally invasive surgery for treatment of craniosynostosis. RECENT FINDINGS: Minimally invasive procedures are well tolerated treatment options for patients with craniosynostosis. Suturectomy and helmet therapy is a treatment option for scaphocephaly with minimal blood loss and length of hospital stay. Spring-mediated cranioplasty is, in addition, a well tolerated and effective treatment option for scaphocephaly. SUMMARY: In patients with multiple suture craniosynostosis, surgical techniques that utilize spring-assisted surgery can provide decreased morbidity with better bone formation made available for a second operation. Continued basic science research and clinical studies will expand the use and provide further minimally invasive procedures to infants with craniosynostosis.

Mechanical tissue resuscitation at the site of traumatic brain injuries reduces the volume of injury and hemorrhage in a swine model.

BACKGROUND: Traumatic brain injuries (TBIs) continue to be a devastating problem with limited treatment options. Previous research applying controlled vacuum to TBI in a rat model resulted in smaller injuries and more rapid recovery. OBJECTIVE: To examine the effects of the application of a controlled vacuum (mechanical tissue resuscitation) to TBI in a large-animal model. The magnitude of vacuum, length of application, and length of delay between injury and the application of mechanical tissue resuscitation were investigated. METHODS: Localized, controlled cortical injuries were created in swine. Vacuums of -50 and -100 mm Hg were compared. Mechanical tissue resuscitation for 3 or 5 days was compared. Delays of 0, 3, or 6 hours between the creation of the TBI and the initiation of mechanical tissue resuscitation were examined. Analysis included histological assessments, computed tomographic perfusion, and magnetic resonance imaging (T2, proton magnetic spectra). RESULTS: A -100 mm Hg vacuum resulted in significantly smaller mean contused brain and hemorrhage volumes compared with -50 mm Hg and controls. Magnetic resonance spectra of treated animals returned to near baseline values. All 10 animals with 5-day mechanical tissue resuscitation treatment survived. Three of 6 animals treated for 3 days died after the discontinuation of treatment. A 3-hour delay resulted in similar results as immediate treatment. A 6-hour delay produced significant, but lesser responses. CONCLUSION: Application of mechanical tissue resuscitation to TBI was efficacious in the large-animal model. Application of -100 mm Hg for 5 days resulted in significantly improved outcomes. Delays of up to 3 hours between injury and the initiation of treatment did not diminish the efficacy of the mechanical tissue resuscitation treatment.

Interstitial-matrix edema in burns: mechanistic insights from subatmospheric pressure treatment in vivo.

Thermal injury disrupts fluid homeostasis and hydration, affecting hemodynamics and local interstitial fluid-driving forces, leading rapidly to edema. This study explores local mechanisms in vivo, after deep partial-thickness burns in the dermal matrix. Heat-damaged skin was obtained from pig corpses, byproducts of unrelated burn treatment protocols approved by the Institutional Animal-Care-and-Use Committee. Hydration potential and flow rates were measured by osmotic stress techniques at 4 and 37 °C, and collagen folding/unfolding was examined by differential scanning calorimetry and diffusion tensor magnetic resonance imaging. Kinetic and equilibrium hydration parameters differed in heat-damaged and undamaged skin; the mean hydration potential and initial flow rates of damaged skin were negative at 37 but positive at 4 °C, in contrast to the positive mean at either temperature of explants taken from undamaged skin sites on the same animals. After subatmospheric pressure treatment (125 mmHg), parameters in damaged reversed to values similar to those of undamaged, whereas the proportion of folded collagen and unidirectional resistance to water diffusion increased. Together, results support interfacial rather than colloidosmotic fluid transfer mechanisms in burns and confirm in vivo the relevance of collagen folding/unfolding, further suggesting collagen structural transitions as potential therapeutic targets and models for engineered biomimetic materials.

Mechanical tissue resuscitation protects against myocardial ischemia-reperfusion injury.

BACKGROUND AND AIM: Reperfusion injury is a complex inflammatory response involving numerous mechanisms and pathways. Mechanical tissue resuscitation is a newly described therapeutic strategy that reduces reperfusion injury. This study further investigates potential mechanisms for the protective effects of mechanical tissue resuscitation while utilizing a bio-absorbable matrix. METHODS: Anesthetized swine were subjected to 80 minutes of coronary ischemia and three hours of reperfusion. An absorbable matrix was used to cover the ischemic-reperfused myocardium and apply the mechanical tissue resuscitation (-50 mmHg) throughout reperfusion. Infarct size, myocardial blood flow (microspheres), apoptosis, edema, and hemodynamics were analyzed. RESULTS: Both control and treated groups displayed similar hemodynamics and physiologic parameters. Mechanical tissue resuscitation significantly reduced early infarct size (16.6 ± 3.8% vs. 27.3 ± 2.5% of area at risk, p < 0.05). This reduction of infarct size was accompanied by reduced edema formation in both epicardial (27% reduction) and endocardial (58% reduction) samples. Histological examination of both epicardial and endocardial tissues also revealed a reduction in apoptosis (80% and 44% reductions) in MTR-treated hearts. CONCLUSIONS: Treatment with mechanical tissue resuscitation during reperfusion reduces both early cell death and the delayed, programmed cell death after ischemia-reperfusion. This cardioprotection is also associated with a significant reduction in interstitial water. Additional cardioprotection may be derived from mechanical tissue resuscitation-induced increased blood flow. Mechanical tissue resuscitation, particularly with a resorbable device, is a straightforward and efficacious mechanical strategy for decreasing cardiomyocyte death following myocardial infarction as an adjunctive therapy to surgical revascularization.

Properties of single electrospun poly (diol citrate)-collagen-proteoglycan nanofibers for arterial repair and in applications requiring viscoelasticity.

Single nanofibers with chemical and functional properties consistent with artery extracellular matrix nanofibers were produced by electrospinning. Using weight ratios to mimic artery extracellular matrix, five materials were tested: (1) Collagen type I, (2) Collagen type I + Collagen type III, (3) Collagen type I + poly (diol citrate), (4) Collagen type I + Collagen type III + poly (diol citrate), and (5) Collagen type I + poly (diol citrate) + Decorin + Aggrecan. Fiber sizes for all materials ranged from 50 nm to 600 nm and random fiber mats had pore sizes from 21 to 40 = m(2) and porosities of 72-84%. Human embryonic palatal mesenchymal cells fibroblasts adhered to all fibers and proliferated over a 7-day study period. Mechanical properties of single fibers were investigated using a combined atomic force/optical microscope. Materials containing poly (diol citrate) showed elasticity increased 3.2 fold greater than composites without poly (diol citrate). Maximum stress was within functional range in comparison to decellularized artery extracellular matrix fibers. By incorporating poly (diol citrate) and proteoglycan along with collagen, a viscoelastic nanofibrous material was produced for use in tissues such as artery where viscoelasticity and tensile strength are required.

Vacuum-assisted closure for complex cranial wounds involving the loss of dura mater.

The aim in this study was to describe the safety and efficacy of vacuum-assisted closure (VAC) in patients with complex cranial wounds with extensive scalp, bone, and dural defects who were not candidates for immediate free tissue transfer. Five patients (4 men and 1 woman) ages 24-73 years with complex cranial wounds were treated with VAC at Wake Forest Baptist Medical Center. Etiologies included trauma, squamous cell carcinoma, and malignant meningioma. Cutaneous wound defects measured as large as 15 cm in diameter. Four of the 5 patients had open skull defects with concomitant dural defects, and 1 patient had dural dehiscence. After surgical debridement, all 5 patients were treated with the direct application of a VAC device to a reapproximated dura mater (1 patient), to a pericranial flap (1 patient), or to a regenerative tissue matrix overlying CNS tissue (3 patients). In all cases involving open cranial wounds, the VAC device promoted granulation tissue formation over the dural substitute, prevented CSF leakage, and kept the wounds free from local infection. The duration of VAC therapy ranged from 16 to 91 days. Although VAC therapy was intended as a temporary measure until these patients could be stabilized for larger tissue transfer procedures or they succumbed to their primary pathology, 1 patient had a successful skin graft following VAC therapy. Hydrocephalus requiring shunt placement developed in 2 patients during VAC therapy. The VAC dressings applied to a tissue matrix or other barrier over brain tissue in extensive cranial wounds are safe and well tolerated, providing a functional barrier and preventing infection.

Collagen unfolding accelerates water influx, determining hydration in the interstitial matrix.

In the interstitial matrix, collagen unfolding at physiologic temperatures is thought to facilitate interactions with enzymes and scaffold molecules during inflammation, tissue remodeling, and wound healing. We tested the hypothesis that it also plays a role in modulating flows and matrix hydration potential. After progressively unfolding dermal collagen in situ, we measured the hydration parameters by osmotic stress techniques and modeled them as linear functions of unfolded collagen, quantified by differential scanning calorimetry after timed heat treatment. Consistent with the hypothetical model, the thermodynamic and flow parameters obtained experimentally were related linearly to the unfolded collagen fraction. The increases in relative humidity and intensity of T(2) maps were also consistent with interfacial energy contributions to the hydration potential and the hydrophobic character of the newly formed protein/water interfaces. As a plausible explanation, we propose that increased tension at interfaces formed during collagen unfolding generate local gradients in the matrix that accelerate water transfer in the dermis. This mechanism adds a convective component to interstitial transfer of biological fluids that, unlike diffusion, can speed the dispersion of water and large solutes within the matrix.

Influence of frontosphenoidal suture synostosis on skull dysmorphology in unicoronal suture synostosis.

Severity of the Harlequin deformity seen in unicoronal synostosis may be augmented when frontoparietal suture synostosis has an associated fusion of the frontosphenoidal suture or in cases of isolated frontosphenoidal synostosis. The purpose of the current study is to characterize various suture fusion patterns along the coronal ring using a modified orbital index (MOI), orbital angle (OA), and endocranial base (EB) angle.This study is a retrospective single institution cohort study. Charts were reviewed over the past 12 years; patients with isolated UCS were included. MOI, OA, and EB were used to identify 3 groups of UCS patients.Twenty-one patients were identified for inclusion in skeletal dysmorphology analysis using MOI, OA, and EB measures. Frontoparietal synostosis patients were diagnosed at significantly younger ages than frontoparietal + frontosphenoidal patients (P = 0.0001). Ipsilateral MOI measures were more severe for frontoparietal patients compared with frontoparietal + frontosphenoidal patients (P = 0.0239). There was a trend for more severe ipsilateral OA measures in frontoparietal patients compared with frontoparietal + frontosphenoidal patients (P = 0.181).Modified orbital index, OA, and EB measurements are useful in the diagnosis of suture fusion patterns in UCS patients. Frontoparietal synostosis has more severe Harlequin deformity compared with frontoparietal + frontosphenoidal patients. Frontosphenoidal fusion coinciding with frontoparietal synostosis may blunt the severity of skeletal dysmorphology in UCS patients and be associated with a delayed diagnosis. Attention must be paid to assessing the frontosphenoidal suture to assure adequate surgical release.

AlloDerm revision for failed pharyngoplasty.

Velopharyngeal insufficiency (VPI) occurs in more than 20% of patients with a cleft palate after primary palatoplasty. Surgical treatment focuses on pharyngoplasty to narrow the nasopharyngeal space and to decrease the distance needed for palatal closure. Persistent VPI after pharyngoplasty affects more than 20% of patients.From September 2007 to December 2009, 16 children (10 boys and 6 girls) with a mean age of 9.5 years (4-15 years) underwent surgical revision using an AlloDerm sling for persistent VPI after at least 1 previous failed pharyngoplasty. Ten children had previous sphincter pharyngoplasties, and 6 had previous pharyngeal flaps. Surgical technique involves creation of a submucosal tunnel through the limbs of the previous pharyngoplasty or pharyngeal flap. A strip of AlloDerm is threaded circumferentially, and the port is adjusted to the desired aperture.All patients underwent preoperative and postoperative analysis of VPI, including oral pharyngeal and perceptual speech examination by speech pathology with a mean follow-up of 441 days. Acoustic nasometry was used to objectively compare preoperative and postoperative nasalance values. A significant improvement in perceptual resonance was seen in 93.8% of patients, and 87.5% of patients improved to normal or mild resonance (P < 0.001). There was a significant mean reduction of nasalance using the MacKay-Kummer Simplified Nasometric Assessment Procedure test (P < 0.001). Two patients developed postoperative flap dehiscence, with one being revised ultimately to have normal speech resonance.Revision pharyngoplasty using an AlloDerm sling can safely and effectively improve speech in patients with persistent VPI after failed pharyngoplasty. Long-term follow-up studies are ongoing.