ABSTRACT
In-stent restenosis (ISR) often occurs after applying drug eluting stents to the blood vessels suffering from atherosclerosis or thrombosis. For treatment of ISR, drug eluting balloons (DEB) have been developed to deliver anti-proliferative drugs to the lesions with ISR. However, there are still limitations of DEB such as low drug delivery efficiency and drug loss to blood flow. Although most researches have focused on alteration of drug formulation for more efficient drug delivery, there are few studies that have attempted to understand and utilize the contact modality of DEB drug delivery. Here, we developed a linear micro-patterned DEB (LMDEB) that applied higher contact pressure to enhance drug stamping to vascular tissue. Ex vivo and in vivo studies confirmed that higher contact pressure from micro-patterns increased the amount of drug delivered to the deeper regions of vessel. Finite element method simulation also showed significant increase of contact pressure between endothelium and micro-patterns. Quantitative analysis by high performance liquid chromatography indicated that LMDEBs delivered 2.3 times higher amount of drug to vascular tissue in vivo than conventional DEBs. Finally, efficacy studies using both atherosclerotic and ISR models demonstrated superior patency of diseased vessels treated with LMDEB compared to those treated with DEB.
Subject(s)
Coronary Restenosis/drug therapy , Drug Delivery Systems/methods , Drug-Eluting Stents/adverse effects , Percutaneous Coronary Intervention/instrumentation , Percutaneous Coronary Intervention/methods , Angioplasty, Balloon, Coronary , Animals , Atherosclerosis/chemically induced , Atherosclerosis/surgery , Chromatography, Liquid , Coronary Angiography , Coronary Restenosis/diagnostic imaging , Disease Models, Animal , Iliac Artery/diagnostic imaging , Iliac Artery/surgery , Male , Mass Spectrometry , Microscopy, Confocal , Microscopy, Fluorescence , Paclitaxel/therapeutic use , Pressure , Rabbits , Swine , Swine, Miniature , Treatment OutcomeABSTRACT
The aim of the present preclinical study was to investigate the capability of a new formulation of biphasic calcium phosphate (BCP) in achieving new bone formation either by itself or in combination with different concentrations of growth factors. Twenty-four 3-month-old male New Zealand white rabbits (weight range, 2.5 to 3.0 kg) that had been bred exclusively for biomedical research purposes and obtained from a licensed vendor were used. Four calvarial defects were created in each animal, for a total of 96 defects. Each defect received alloplastic BCP (Osteon III, Genoss) that was composed of 60% hydroxyapatite and 40% ß-tricalcium phosphate) (porosity, ~80%; macropore size, 200 to 400 µm; crystallinity, 95%) combined with different concentrations of recombinant human platelet-derived growth factor BB (rhPDGF-BB), human recombinant basic fibroblast growth factor-2 (rhFGF-2), or recombinant human bone morphogenetic protein-2 (rhBMP-2). A custom-made polycarbonate tube was fixed to each defect site by applying slight pressure, and a mixture of bone graft and growth factor was implanted into the tubes. Data were collected 2, 4, and 8 weeks after creation of the defects to assess early and late healing. Various amounts of newly formed bone and remnant BCP particles formed inside of the tube throughout the study period. The BCP + 0.5 mg/mL rhBMP-2 group exhibited the most bone formation. At 8 weeks, more new bone formation was noted in the Osteon III + rhBMP-2 combined group than in other groups. The present study results indicate that BCP can be combined with different concentrations of rhBMP-2, rhFGF-2, and rhPDGF-BB to produce new bone formation within a polycarbonate tube in calvarial defects in a rabbit model.
Subject(s)
Bone Regeneration , Osteogenesis , Skull/pathology , Animals , Becaplermin , Bone Morphogenetic Protein 2/therapeutic use , Durapatite , Fibroblast Growth Factor 2 , Fibroblast Growth Factors , Humans , Hydroxyapatites/therapeutic use , Male , Proto-Oncogene Proteins c-sis , Rabbits , Recombinant Proteins/therapeutic useABSTRACT
A new surface modification that facilitates the grafting of poly(ethylene glycol) methacrylate (PEGMA) on a polyurethane (PU) surface was developed using a thiol-ene reaction. The thiolated PU surface for the grafting of PEGMA was created by fabricating allylated PU through an allophanate reaction, which was then modified with tetra-thiols to enhance the functionality of the PU surface. The amount of thiol groups increased with increasing irradiation time, and its concentration was almost equilibrated after 30 min irradiation. ESCA spectra revealed new two peaks on the thiolated PU surface at 163 and 228 eV, which was assigned to sulfur, and a significant increase in the oxygen content of the poly(PEGMA)-grafted PU was shown as compared with the other groups. Also, the irradiation time-dependent increase in the surface wettability of poly(PEGMA)-grafted PU was confirmed by contact angle measurement. These surface characteristics support that poly(PEGMA)-grafted PU was successfully prepared using a thiol-ene reaction. For in vitro protein adsorption and cell proliferation tests, the poly(PEGMA)-grafted PU surface showed repellent properties against both fibrinogen and smooth muscle cells, compared to other groups. This surface graft polymerization of PEGMA on a PU surface via a thiol-ene reaction can be used as a promising surface modification for improving blood compatibility of PU-based blood-contacting devices.
