Impact of preprocedural mesenteric artery stenosis and mesenteric ischemia in patients undergoing transcatheter aortic valve replacement.

OBJECTIVES: We aimed to examine the incidence, etiologies, and consequences of acute mesenteric ischemia as well as the impact of preprocedural subclinical mesenteric artery stenosis in patients undergoing transcatheter aortic valve replacement. METHODS: Among prospective follow-up of 269 consecutive patients undergoing transcatheter aortic valve replacement, diagnosis of acute mesenteric ischemia was confirmed by abdominal computed tomography. Cumulative hazard of 1-year all-cause and cardiovascular mortality according to the absence or presence of mesenteric artery stenosis 70% or greater from preprocedural computed tomography angiography was analyzed. RESULTS: Acute mesenteric ischemia was confirmed in 7 patients (2.6%) during mid-term (median, 33.3 months, interquartile range, 15.0-61.0 months) follow-up. Thrombotic occlusions of previously stenotic mesenteric arteries account for 4 cases (57.1%), and embolic acute mesenteric ischemia constitute the rest (42.9%) of the cases. The mortality rate of acute mesenteric ischemia was 100%. At 30 days, death from acute mesenteric ischemia accounts for 40% of all-cause mortality and 67% of cardiovascular death. By multivariable analysis, higher Society of Thoracic Surgeons score and mesenteric artery stenosis 70% or greater were independently associated with acute mesenteric ischemia. Thirty-two patients (11.9%) with preprocedural mesenteric artery stenosis 70% or greater had an increased risk of all-cause mortality (adjusted hazard ratio, 3.78; 95% confidence interval, 1.74-8.19; P = .001) at 1 year after transcatheter aortic valve replacement. CONCLUSIONS: Acute mesenteric ischemia, an important cause of 30-day mortality, should be considered in patients who become clinically unstable after transcatheter aortic valve replacement, particularly but not exclusively in those with preexisting mesenteric artery stenosis. Mesenteric artery stenosis should be routinely assessed in all patients who are indicated for transcatheter aortic valve replacement considering the dismal prognosis of acute mesenteric ischemia.

Hyaluronic acid-dependent protection against alkali-burned human corneal cells.

Hyaluronic acid (HA) is a high-molecular-weight glycosaminoglycan and extracellular matrix component that promotes cell proliferation. This study aimed to evaluate the effects of HA on alkali-injured human corneal epithelial cells in vitro, and to elucidate the mechanisms by which HA mediates corneal cell protection. A human corneal epithelial cell line (HCE-2) was treated with sodium hydroxide before incubation with low-molecular-weight HA (LMW-HA, 127 kDa) or high-molecular-weight HA (HMW-HA, 1525 kDa). A global proteomic analysis was then performed. Our data indicated that HA treatment protects corneal epithelial cells from alkali injury, and that the molecular weight of HA is a crucial factor in determining its effects. Only HMW-HA reduced NaOH-induced cytotoxic effects in corneal cells significantly and increased their migratory and wound healing ability. Results from 2D-DIGE and MALDI-TOF/TOF MS analyses indicated that HMW-HA modulates biosynthetic pathways, cell migration, cell outgrowth, and protein degradation to stimulate wound healing and prevent cell death. To our knowledge, our study is the first to report the possible mechanisms by which HMW-HA promotes repair in alkali-injured human corneal epithelial cells.

Biodegradable micelles from a hyaluronan-poly(ε-caprolactone) graft copolymer as nanocarriers for fibroblast growth factor 1.

A novel copolymer (HA-g-PCL) was prepared by grafting hydrophobic poly(ε-caprolactone) (PCL) chains onto the backbone of hydrophilic hyaluronic acid (HA) with a grafting ratio of ∼7%. The copolymer formed micelles with a size of ∼60 nm in aqueous solution over a critical concentration of ∼4 µg mL-1. Each micelle consisted of about four copolymer chains. Fibroblast growth factor 1 (FGF1) may be encapsulated in micelles by various methods. In particular, FGF1 loaded to micelles through 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) conjugation provided efficient (∼87%) and large amount (up to ∼175 µg FGF1 per mg HA-g-PCL, or on average one FGF1 molecule per micelle) of loading as well as reduced burst release of FGF1. FGF1-loaded micelles remained functional after 21 days. Experimental rats receiving FGF1-loaded micelles showed better wound contraction and faster sebaceous gland formation than those receiving free FGF1 or empty micelles. We conclude that novel HA-g-PCL micelles are good nanocarriers for the controlled release of FGF1 and may be applied to encapsulate other bioactive molecules for therapeutic purposes.

Characterizing poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for doxorubicin (DOX) delivery: effects of crosslinked of amine groups.

New amine-groups containing tri-block copolymers and micelles that consisting of poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCL-b-COS-b-PEG, PCP), were synthesized, characterized, and evaluated for delivering doxorubicin (DOX) with or without crosslinked amine groups by genipin. The characteristics of the PCP copolymers of Fourier-transform infrared spectrometry (FT-IR) verify the amine and ester groups of the COS and the PCL of the copolymers, respectively. 1H nuclear magnetic resonance (1H NMR) spectra verify the structures of the PCP copolymers consisting two PCL and PEG polymers reacted onto the COS block. In addition, gel permeation chromatography (GPC) determines the number average molecular weight of the tri-block copolymers (Mn) of approximately 11340 Da/mole. The PCP copolymers can self-assemble to form polymeric micelles at the critical micelle concentration (CMC) of 1.0 microM as determined by the UV-VIS absorption spectra. The mean diameter of the PCP micelles is 90 nm, as determined using a dynamic light-scattering (DLS) analyzer. Moreover, the zeta potentials of PCP micelles change from neutral to cationic state when pH of suspension mediums varied from 7.4 to 3.0. For evaluating delivery characteristics of hydrophobic DOX, it was loaded into PCP micelles with or without crosslinked by genipin. The burst release and release period of DOX for the crosslinked micelles are significantly reduced (P < 0.003, n = 3, for pH = 7.4) and sustained (e.g., 8 days), respectively, than those non-crosslinked ones (e.g., 4 days). In conclusion, new tri-block amine groups containing PCP copolymers are synthesized that can self-assemble as PCP micelles. After post-crosslinked amine groups of DOX loaded the micelles, they can effectively reduce the burst release and sustain the release of DOX at different pH dissolution mediums. Further applications of PCP copolymers and micelles for drug delivery can be explored in future.

Reinnervation of muscular targets by nerve regeneration through guidance conduits.

We established histopathologic and neurophysiologic approaches to examine whether different designs of polycaprolactone-engineered nerve conduits (hollow vs. laminated) could promote nerve regeneration as autologous grafts after transection of sciatic nerves. The assessments included morphometric analysis at the level of sciatic nerve, neuromuscular junction (NMJ) and gastrocnemius muscle, and nerve conduction studies on sciatic nerves. Six months after nerve grafting, the nerve fiber density in the hollow-conduit group was similar to that in the autologous-graft group; the laminated-conduit group only achieved approximately 20% of these values. The consequences of these differences were reflected in nerve growth into muscular targets; this was demonstrated by combined cholinesterase histochemistry for NMJ and immunohistochemistry for nerve fibers innervating NMJ with an axonal marker, protein gene product 9.5. Hollow conduits had similar index of NMJ innervation as autologous grafts; the values were higher than those of laminated conduits. Among the 3 groups there were same patterns of differences in the cross-sectional area of muscle fibers and amplitudes of compound muscle action potential. These results indicate that hollow conduits were as efficient as autologous grafts to facilitate nerve regeneration, and provide a multidisciplinary approach to quantitatively evaluate muscular reinnervation after nerve injury.

Reduction in experimental peridural adhesion with the use of a crosslinked hyaluronate/collagen membrane.

The research goals were to fabricate a crosslinked hyaluronate (HA)/collagen membrane and study its efficacy in preventing peridural adhesion. Different weight ratios of HA/collagen membranes crosslinked with carbodiimide were tested for biocompatibility and biodegradability first. Forty-eight adult New Zealand white rabbits underwent an L6 laminectomy. Sixteen rabbits each received a weight ratio of HA/collagen = 60/40 membrane (Membrane A) or a 40/60 membrane (Membrane B) on the exposed dura. The last 16 rabbits received no treatment and served as controls. No adverse reaction of the membranes was noted. Magnetic resonance images revealed a hyposignal space between the dura and the scar tissues at Membrane B-treated laminectomy site 3 months after surgery. Histological examination showed that the amount of scarring decreased with time in all groups. Amount of scarring decreased significantly at laminectomy sites treated with either membrane. Compared with the control group, the extent of peridural adhesion decreased significantly in the Membrane B-treated group at 3 months after surgery; while it decreased substantially, but not significantly, in the Membrane A-treated group. The carbodiimide-crosslinked HA/collagen membrane is a safe and effective antiadhesive material in vivo. When placed onto the laminectomy site, the membrane with a weight ratio of HA/collagen = 40/60 appears to reduce peridural scar adhesion.

Fabrication of porous biodegradable polymer scaffolds using a solvent merging/particulate leaching method.

This study developed a solvent merging/particulate leaching method for preparing three-dimensional porous scaffolds. Poly(L-lactic-co-glycolic acid) (PLGA) and sodium chloride particles were dry-mixed and cast into a special mold, through which a liquid could pass due to a pressure difference. An organic solvent was then poured into the mold to dissolve and merge the PLGA particles under negative pressure. A nonsolvent was conducted into the PLGA/salt composite to solidify and precipitate the merged PLGA matrix. Finally, a large amount of water was passed through the mold to leach out the salt particles so as to create a porous structure. The results revealed that a highly porous three-dimensional scaffold (>85 vol %) with a well interconnected porous structure could be achieved by this process. Porosity and the pore size of the scaffold were controlled using the ratio and the particle size of the added salt particles. A larger-volume scaffold was produced using a larger mold. This work provides a continuous and simple procedure for fabricating a bulk three-dimensional porous scaffold for tissue engineering.