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表面转化型骨诱导性聚对苯二甲酸乙二醇酯支架作为局部抗生素递送的双重系统用于骨组织再生。

Surface-transformed osteoinductive polyethylene terephthalate scaffold as a dual system for bone tissue regeneration with localized antibiotic delivery.

机构信息

Department of Polymer Science and Rubber Technology, Cochin University of Science and Technology, Kerala 682 022, India.

Division of Artificial Internal Organs, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695 012, India.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110491. doi: 10.1016/j.msec.2019.110491. Epub 2019 Nov 28.

Abstract

Multifunctional scaffolds have recently attained superior significance in tissue regeneration due to combinational activity profile that is usually accomplished by separate sequential therapy. Here, we present a dual system comprised of surface-phosphorylated PET fibrous matrix coated with ciprofloxacin-impregnated biodegradable polymer poly (hydroxyethyl methacrylate) aiming at regeneration of bone tissue deprived of bacterial infections, particularly osteomyelitis. The ATR, XPS and FESEM/EDX results provided confirmative evidences for surface phosphorylation of PET and in situ coating of the polymer. Swelling and contact angle measurements demonstrated improved hydrophilicity which is further corroborated by in vitro degradation profile in PBS. Preliminary evaluation by MTT and actin staining proved its biocompatibility while enhanced in vitro mineralization in 1.5X SBF by FESEM/EDX clearly indicate the primary nucleation and secondary growth of beautiful apatite crystals with Ca/P ratio similar to human bone. Alizarin red S and von Kossa staining validated the biomineralization in MG-63 cells. The sequential expression of early and late biomarkers -alkaline phosphatase (ALP) and osteocalcin (OSN)- of osteoblast differentiation in rat bone marrow mesenchymal cells (BMC) has demonstrated osteoinductive nature of the system. The second functionality of the scaffold has been proven by step-wise ciprofloxacin-release profile (in vitro) with ~60% release within 120 h. In addition, antibacterial studies of ciprofloxacin- eluted from the scaffold have shown apparent zones of inhibition against Staphylococcus aureus (3.6 ± 0.3 cm) and Escherichia coli (3.0 ± 0.8 cm). Hence, the surface-transformed PET scaffold function as a dual system as localized antibiotic delivery vehicle against bone infections and undergo self-biomineralization leading to osteoinduction.

摘要

多功能支架由于其组合的活性谱在组织再生中最近获得了重要意义,通常通过单独的序贯治疗来实现。在这里,我们提出了一个由表面磷酸化的 PET 纤维基质组成的双系统,该基质涂有载有环丙沙星的可生物降解聚合物聚(羟乙基甲基丙烯酸酯),旨在再生没有细菌感染的骨组织,特别是骨髓炎。ATR、XPS 和 FESEM/EDX 结果为 PET 的表面磷酸化和聚合物的原位涂覆提供了确凿的证据。溶胀和接触角测量表明亲水性得到了改善,这进一步通过在 PBS 中的体外降解谱得到证实。MTT 和肌动蛋白染色的初步评估证明了其生物相容性,而在 1.5X SBF 中的体外矿化增强通过 FESEM/EDX 清楚地表明了具有类似人骨 Ca/P 比的美丽磷灰石晶体的初级成核和次级生长。茜素红 S 和 von Kossa 染色验证了 MG-63 细胞中的生物矿化。大鼠骨髓间充质细胞(BMC)中成骨细胞分化的早期和晚期生物标志物碱性磷酸酶(ALP)和骨钙素(OSN)的顺序表达证明了该系统的成骨诱导特性。支架的第二个功能已通过逐步释放环丙沙星的体外释放曲线(120 小时内约 60%释放)得到证明。此外,从支架洗脱的环丙沙星的抗菌研究表明,对金黄色葡萄球菌(3.6±0.3cm)和大肠杆菌(3.0±0.8cm)有明显的抑制区。因此,表面转化的 PET 支架作为局部抗生素输送载体对抗骨感染,并通过自我生物矿化导致成骨诱导。

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