RESUMO
An increasing number of studies have shown that the local release of nitric oxide (NO) from hydrogels stimulates tissue regeneration by modulating cell proliferation, angiogenesis, and inflammation. The potential biomedical uses of NO-releasing hydrogels can be expanded by enabling their application in a fluid state, followed by controlled gelation triggered by an external factor. In this study, we engineered a hydrogel composed of methacrylated hyaluronic acid (HAGMA) and thiolated gelatin (GELSH) with the capacity for in situ photo-cross-linking, coupled with localized NO release. To ensure a gradual and sustained NO release, we charged the hydrogels with poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with S-nitrosoglutathione (GSNO), safeguarding SNO group integrity during photo-cross-linking. The formation of thiol-ene bonds via the reaction between GELSH's thiol groups and HAGMA's vinyl groups substantially accelerated gelation (by a factor of 6) and increased the elastic modulus of hydrated hydrogels (by 1.9-2.4 times). HAGMA/GELSH hydrogels consistently released NO over a 14 day duration, with the release of NO depending on the hydrogels' equilibrium swelling degree, determined by the GELSH-to-HAGMA ratio. Biocompatibility assessments confirmed the suitability of these hydrogels for biological applications as they display low cytotoxicity and stimulated fibroblast adhesion and proliferation. In conclusion, in situ photo-cross-linkable HAGMA/GELSH hydrogels, loaded with PLGA-GSNO nanoparticles, present a promising avenue for achieving localized and sustained NO delivery in tissue regeneration applications.
Assuntos
Gelatina , Ácido Hialurônico , Ácido Hialurônico/química , Gelatina/química , Óxido Nítrico , Hidrogéis/farmacologia , Hidrogéis/química , Compostos de Sulfidrila/químicaRESUMO
The design of bioresorbable vascular stents (BVS) capable of releasing nitric oxide (NO) at the implant site may enable BVS to mimic the antiplatelet, antiproliferative, and pro-endothelial actions of NO, overcoming complications of BVS such as late thrombosis and restenosis. In this study, the fabrication of BVS composed of methacrylated poly(dodecanediol citrate-co-dodecanediol S-nitroso-mercaptosuccinate) (mP(DC-co-DMSNO)), a novel elastomeric, bioabsorbable, and photocurable copolyester, containing covalently bound S-nitrosothiol groups in the carbon backbone of the polymer, is reported. The mP(DC-co-DMSNO) stents are manufactured via photoinduced 3D printing and allow deployment via a self-expansion process from a balloon catheter. After deployment, hydration of the stents triggers the release of NO, which is maintained during the slow hydrolysis of the polymer. Real-time NO release measurements show that by varying the copolyester composition and the strut geometry of the mP(DC-co-DMSNO) stents, it is possible to modulate their NO release rate in the range of 30-52 pmol min-1 cm-2 . Preliminary biological assays in cell culture show that endothelial cells adhere to the surface of the stents and that NO release favors their endothelization. Thus, mP(DC-co-DMSNO) may emerge as a new platform for the fabrication of advanced BVS.
Assuntos
Implantes Absorvíveis , Stents Farmacológicos , Óxido Nítrico , Células Endoteliais , Resultado do Tratamento , Stents , Impressão Tridimensional , PolímerosRESUMO
A thermal protocol is reported for the formal insertion of nitric acid into aryldiazoacetates using Fe(NO3)3·9H2O. This strategy is mild and high yielding and allows the preparation of a large variety of members of an unprecedented family of organic nitrates. The nitrate group can be also readily transformed into other functional groups and heterocyclic moieties and can possibly allow new biological explorations of untapped potential associated with their NO-releasing ability.
RESUMO
INTRODUCTION: Orbital compartment syndrome (OCS) is a rare condition characterized by increased intraorbital pressure and hypoperfusion of critical neural structures. It is usually associated with external ophthalmoplegia. We report a case of postoperative OCS following a frontotemporal craniotomy and review pertinent literature. CASE DESCRIPTION: A 3-year-old female patient presented with a 3-year history of refractory epilepsy and diagnosis of right frontobasal cortical dysplasia. She underwent an elective frontotemporal craniotomy to allow resection of dysplastic cortex. The intraoperative period was uneventful. Postoperatively, following removal of operating fields, we noticed proptosis and right periorbital swelling. A diagnosis of orbital compartment syndrome was made. At the pediatric intensive care unit, the patient underwent an emergency right lateral canthotomy with wide inferior and superior cantholysis. Nowadays she is in the fourth month of postoperative follow-up. There is still slight and almost indistinguishable exophthalmos, but her extrinsic eye movement ranges and reaction to light are normal. DISCUSSION: OCS is a rare ophthalmologic emergency characterized by an acute rise in orbital pressure and may result in complete irreversible blindness if not rapidly treated. The frontotemporal or "pterional" craniotomy exposure requires a myocutaneous flap to be retracted anteriorly and inferiorly near the orbit. There may be orbital compression due to this flap leading to potential harmful complications. Attention to factors such as direct ocular pressure from skin flaps, congestion from head positioning, and adequate intraoperative eye protection may reduce the risk or allow faster management.
Assuntos
Síndromes Compartimentais/etiologia , Craniotomia/efeitos adversos , Descompressão Cirúrgica/efeitos adversos , Pré-Escolar , Síndromes Compartimentais/cirurgia , Epilepsia/cirurgia , Feminino , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
BACKGROUND: Calcifying nonneoplastic pseudoneoplasms of the neuraxis (CAPNON) have been reported in 59 cases in literature, however, they rarely involve the spinal cord. Owing to the advances in immunohistochemical markers, their structure and origin are better understood now. CASE REPORT: We present the case of a 72-year-old female who had longstanding history of low back pain that exacerbated 20 days prior to the presentation to the emergency room with a frank cauda equina syndrome. The lumbar computed tomography scan showed a hyperdense lesion, suggestive of calcified tumor, whereas the magnetic resonance imaging revealed a hypointense lesion on theT1 and T2-weighted images, without contrast enhancement or edema on fluid-attenuated inversion recovery. She underwent an emergent L2-L4 laminectomy and L3-L4 discectomy with resection of L2 intradural tumor, following which she regained normal function. CONCLUSION: A 72-year-old female presented with a cauda equina syndrome attributed to an L2 intradural CAPNON. Following gross total resection, the patient was neurologically intact.