具有针对细菌生物膜的有效多药物顺序释放的3D支架
3D scaffold with effective multidrug sequential release against bacteria biofilm
摘要:
骨感染是手术或创伤后的一种令人恐惧的并发症,仍然是一种非常难以处理的疾病。到目前为止,3D植入物的设计可以改善治疗效果,它结合了骨再生和局部多药治疗的优点,以避免细菌生长,耐药性和可怕的副作用。在这里,分层的三维多药物支架的基础上,纳米复合生物陶瓷和聚乙烯醇(PVA)制备的快速成型与外部涂层的明胶-戊二醛(Gel-Glu)已经制造。这些3D支架含有三种抗菌剂(利福平、左氧氟沙星和万古霉素),它们被定位在支架的不同隔室中,以获得不同的释放动力学和更有效的联合治疗。将左氧氟沙星负载在纳米复合生物陶瓷的介孔中,万古霉素定位在PVA生物聚合物部分,利福平负载在Gel-Glu外涂层中。所获得的结果表明,利福平的早期和快速释放,其次是万古霉素和左氧氟沙星,分别持续和延长释放,这主要是由这些支架的逐步在体外降解率。这种联合疗法能够破坏革兰氏阳性和革兰氏阴性细菌生物膜,并抑制细菌生长;此外,这些多功能支架具有优异的生物活性以及良好的生物相容性,在整个表面具有完整的前成骨细胞定植,确保良好的骨再生。这些研究结果表明,这些分层的三维多药物支架是有前途的候选人作为平台的局部骨感染治疗。
英文摘要:
Bone infection is a feared complication following surgery or trauma that remains as an extremely difficult disease to deal with. So far, the outcome of therapy could be improved with the design of 3D implants, which combine the merits of osseous regeneration and local multidrug therapy so as to avoid bacterial growth, drug resistance and the feared side effects. Herein, hierarchical 3D multidrug scaffolds based on nanocomposite bioceramic and polyvinyl alcohol (PVA) prepared by rapid prototyping with an external coating of gelatin-glutaraldehyde (Gel-Glu) have been fabricated. These 3D scaffolds contain three antimicrobial agents (rifampin, levofloxacin and vancomycin), which have been localized in different compartments of the scaffold to obtain different release kinetics and more effective combined therapy. Levofloxacin was loaded into the mesopores of nanocomposite bioceramic part, vancomycin was localized into PVA biopolymer part and rifampin was loaded in the external coating of Gel-Glu. The obtained results show an early and fast release of rifampin followed by sustained and prolonged release of vancomycin and levofloxacin, respectively, which are mainly governed by the progressive in vitro degradability rate of these scaffolds. This combined therapy is able to destroy Gram-positive and Gram-negative bacteria biofilms as well as inhibit the bacteria growth; in addition, these multifunctional scaffolds exhibit excellent bioactivity as well as good biocompatibility with complete cell colonization of preosteoblast in the entire surface, ensuring good bone regeneration. These findings suggest that these hierarchical 3D multidrug scaffolds are promising candidates as platforms for local bone infection therapy.
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