Research On Horn Keratin For The Preparation Of Biodegradable Coronary Stent

Biodegradable stent has been caused a large of attention to many researchersbecause of its potential advantages over conventional bare or drug-coated metallicstents, such as biodegradable polymer stent and biodegradable magnesium-alloy stent.However, the poor mechanical properties of polymer and the too rapid degradation ofmagnesium-alloy have not achieved very good breakthroughs, hindering thedevelopment of biodegradable stent. On the other hand, horn keratins have anexcellent biological model for polymeric nano-structured composite materials with ahierarchically structure which shows a fibrous organization from nanometer tomicrometer scale, resulting that the horn keratins are tough, resilient and highlyimpact resistant. Therefore, it is the first time to propose to use the horn keratin toprepare the biodegradable coronary artery stents, which can provide the importanttheoretical guidance for the application of natural biological material in interventionaltreatment and the preparation of biodegradable stents.At first, the microstructure and mechanical properties of horns derived fromthree domestic bovines (buffalo, cattle and sheep) were examined. The effects ofwater content, sampling position and orientation of three bovid horns on mechanicalproperties were systematically investigated by uniaxial tension and micronindentation tests. Meanwhile, the material composition and metal element contentswere determined by Raman spectroscopy and elemental analysis respectively, and themicrostructures of the horns were measured by scanning electron microscopy (SEM).In this way, the horn keratin with the best mechanical property was chosen for thenext experiment. And then, in order to accelerate the degradation of horn keratin, thebest horn keratin was treated by oxidant. However, for the purpose of the optimumoxidation conditions, the orthogonal experiment was used to explore the effects ofoxidation conditions on the mechanical property of horn keratin. In addition, thecharacterization on their composition, microstructure, and biological responses wereperformed. Thus, a biodegradable horn keratin would be obtained, which wouldcomply with the basic requirements of biodegradable material for stent. At last, the validated analysis of oxidized horn keratin for the possibility of preparing thebiodegradable stent were performed by CAD design software and finite elementanalysis software.The results as follow:1. The mechanical properties of horns have negative correlation with watercontents and depend on sampling position and orientation. The spatial variations ofthe mechanical properties in horns are attributed to the different keratinization degreesin the proximal, middle and distal parts. And the mechanical properties of horns inlongitudinal direction are better than those in transverse. Among the three horns, themechanical properties of buffalo horn are the best, followed by cattle horn, and thosein sheep horn are the worst. This is due to the differences in material composition,metal element, and the microstructures of the horns. But the mechanical properties ofbuffalo horns are not dependent on the source of the buffalo. Therefore, regularengineered buffalo keratinous materials with standard mechanical properties can beobtained from different buffalo horns by using proper preparing methods.2. It is found that the oxidation process could lead the disulfide bond to breakdown and then to form sulfonic acid, or even make partial peptide chain to befragment for the new modification of amino acid. Hence the oxidized horn keratinshave lower thermal stability and hydrolytic stability in comparison with horn keratin,but the degradation products of oxidized horn keratins have no significant difference.In addition, the mechanical properties of oxidized horn keratins are poorer than that ofhorn keratin, but the oxidized horn keratins still have disulphide bonds to form athree-dimensional structure, which benefits for their mechanical properties. Thefracture toughness of oxidized horn keratins increases with the increase in the degreeof oxidation.3. After oxidation, the oxidized horn keratins have lower cytotoxicity and lowerhemolysis ratio. Moreover, when the oxidized horn keratins, as well as differentconcentration of degradation products of oxidized horn keratins, are directly incontact with platelet-rich plasma, platelets are not activated. It suggests that theoxidized horn keratins have good hemocompatibility, without triggering blood thrombosis. The implantation experiment in vivo also demonstrates that the oxidizedhorn keratins are compatible with the tissue, because there are minimal fibrouscapsule and less of infiltration of host cells, without causing serious inflammation. Insummary, the oxidized horn keratins can act as implanted biomaterial devices that aredirectly in contact with blood and tissue.4. Base on the mechanical properties of OH12-20, the results of finite elementanalysis suggest that the designed stent model achieve the substantial requirements ofbiodegradable stent. Therefore, after proper oxidation treatment, the oxidized hornkeratin can be expected to be an excellent biodegradable material for stent which canprovide an important foundation on the development of biodegradable stent.