RESUMEN
While chronic limb-threatening ischemia is a serious peripheral artery disease, the lack of an appropriate stent significantly limits the potential of interventional treatment. In spite of much progress in coronary stents, little is towards peripheral stents, which are expected to be both long and biodegradable and thus require a breakthrough in core techniques. Herein, we develop a long and biodegradable stent with a length of up to 118 mm based on a metal-polymer composite material. To achieve a well-prepared homogeneous coating on a long stent during ultrasonic spraying, a magnetic levitation is employed. In vivo degradation of the stent is investigated in rabbit abdominal aorta/iliac arteries, and its preclinical safety is evaluated in canine infrapopliteal arteries. First-in-man implantation of the stent is carried out in the below-the-knee artery. The 13 months' follow-ups demonstrate the feasibility of the long and biodegradable stent in clinical applications.
Asunto(s)
Implantes Absorbibles , Enfermedad Arterial Periférica , Stents , Animales , Conejos , Perros , Enfermedad Arterial Periférica/terapia , Arteria Ilíaca/cirugía , Aorta Abdominal/cirugía , Polímeros/química , Masculino , Arteria Poplítea/cirugía , HumanosRESUMEN
The new-generation coronary stents are expected to be biodegradable, and then the biocompatibility along with biodegradation becomes more challenging. It is a critical issue to choose appropriate biomimetic conditions to evaluate biocompatibility. Compared with other candidates for biodegradable stents, iron-based materials are of high mechanical strength, yet have raised more concerns about biodegradability and biocompatibility. Herein, a metal-polymer composite strategy is applied to accelerate the degradation of iron-based stents in vitro and in a porcine model. Furthermore, it is found that serum, the main environment of vascular stents, ensured the safety of iron corrosion through its antioxidants. This work highlights the importance of serum, particularly albumin, for an in vitro condition mimicking blood-related physiological condition, when reactive oxygen species, inflammatory response, and neointimal hyperplasia are concerned. The resultant metal-polymer composite stent is implanted into a patient in clinical research via interventional treatment, and the follow-up confirms its safety, efficacy, and appropriate biodegradability.
Asunto(s)
Biomimética , Stents , Porcinos , Animales , Polímeros , Metales , Hierro , Implantes AbsorbiblesRESUMEN
A biodegradable coronary stent is expected to eliminate the adverse events of an otherwise eternally implanting material after vessel remodeling. Both biocorrodible metals and biodegradable polymers have been tried as the matrix of the new-generation stent. Herein, we utilized a metal-polymer composite material to combine the advantages of the high mechanical strength of metals and the adjustable degradation rate of polymers to prepare the biodegradable stent. After coating polylactide (PLA) on the surface of iron, the degradation of iron was accelerated significantly owing to the decrease of local pH resulting from the hydrolysis of PLA, etc. We implanted the metal-polymer composite stent (MPS) into the porcine artery and examined its degradation in vivo, with the corresponding metal-based stent (MBS) as a control. Microcomputed tomography (micro-CT), coronary angiography (CA), and optical coherence tomography (OCT) were performed to observe the stents and vessels during the animal experiments. The MPS exhibited faster degradation than MBS, and the inflammatory response of MPS was acceptable 12 months after implantation. Additionally, we implanted another MPS after 1-year implantation of the first MPS to investigate the result of the MPS in the second implantation. The feasibility of the biodegradable MPS in second implantation in mammals was also confirmed.
Asunto(s)
Implantes Absorbibles , Vasos Coronarios/patología , Hierro/química , Poliésteres/química , Stents , Animales , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Corrosión , Hierro/metabolismo , Ensayo de Materiales , Porcinos , Tomografía de Coherencia ÓpticaRESUMEN
The new principle and technique to tune biodegradation rates of biomaterials is one of the keys to the development of regenerative medicine and next-generation biomaterials. Biodegradable stents are new-generation medical devices applied in percutaneous coronary intervention, etc. Recently, both corrodible metals and degradable polymers have drawn much attention in biodegradable stents or scaffolds. It is, however, a dilemma to achieve good mechanical properties and appropriate degradation profiles. Herein, we put forward a metal-polymer composite strategy to achieve both. Iron stents exhibit excellent mechanical properties but low corrosion rate in vivo. We hypothesized that coating of biodegradable aliphatic polyester could accelerate iron corrosion due to the acidic degradation products, etc. To demonstrate the feasibility of this composite material technique, we first conducted in vitro experiments to affirm that iron sheet corroded faster when covered by polylactide (PLA) coating. Then, we fabricated three-dimensional metal-polymer stents (MPS) and implanted the novel stents in the abdominal aorta of New Zealand white rabbits, setting metal-based stents (MBS) as a control. A series of in vivo experiments were performed, including measurements of residual mass and radial strength of the stents, histological analysis, micro-computed tomography, and optical coherence tomography imaging at the implantation site. The results showed that MPS could totally corrode in some cases, whereas iron struts of MBS in all cases remained several months after implantation. Corrosion rates of MPS could be easily regulated by adjusting the composition of PLA coatings.
Asunto(s)
Stents , Implantes Absorbibles , Animales , Materiales Biocompatibles , Hierro , Metales , Polímeros , Conejos , Microtomografía por Rayos XRESUMEN
A ratiometric fluorescent probe 1 for fluoride ion was developed based on modulation of the excited-state intramolecular proton transfer (ESIPT) process of 2-(2'-hydroxyphenyl)benzimidazole (HPBI) through the hydroxyl group protection/deprotection reaction. The probe 1 was readily prepared by the reaction of HPBI with tert-butyldimethylsilyl chloride (TBS-Cl) and shows only fluorescence emission maximum at 360 nm. Upon treatment with fluoride in aqueous DMF solution, the TBS protective group of probe 1 was removed readily and ESIPT of the probe was switched on, which resulted in a decrease of the emission band at 360 nm and an increase of a new fluorescence peak around 454 nm. The fluorescent intensity ratio at 454 and 360 nm (I(454)/I(360)) increases linearly with fluoride ion concentration in the range 0.3-8.0 micromol L(-1) and the detection limit is 0.19 micromol L(-1). The proposed probe shows excellent selectivity toward fluoride ion over other common anions. The method has been successfully applied to the fluoride determination in toothpaste and tap water samples.