Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.
Designer Dual Therapy Nanolayered Implant Coatings Eradicate Biofilms and Accelerate Bone Tissue Repair.
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设计师双重治疗纳米层植入物涂层根除生物膜并加速骨组织修复。
DOI：
10.1021/acsnano.6b00087
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发表时间：
2016-04-26
期刊：
影响因子：
17.1
通讯作者：
Hammond PT
中科院分区：
文献类型：
--
作者：
Min J;Choi KY;Dreaden EC;Padera RF;Braatz RD;Spector M;Hammond PT
与骨科植入物相关的感染会增加发病率和显著的医疗成本。目前，感染假体翻修关节成形术的黄金标准是一个耗时且昂贵的两阶段手术，需要两个手术步骤和6-8周的关节固定时间。由于感染在种植体置换手术中更为常见，这些问题极大地影响了持续增长的一部分患者的长期护理。在这里，我们证明了一种单阶段修复，使用自组装的、可水解降解的多层涂层的假体，以时间错排的方式顺序递送抗生素（庆大霉素）和骨诱导生长因子（BMP-2），可以根除已建立的生物膜，并在诱导骨髓炎的大鼠植入物周围完成快速的骨组织修复。纳米层结构允许在感染的植入物环境中精确地独立控制每种治疗剂的释放动力学和负载。顶层含有的抗生素可以调整，在早期提供足够的快速释放，以消除感染，随后持续释放数周，潜在的BMP-2成分可以长期持续释放BMP-2，这比短期的突然释放诱导更显著和机械能力强的骨形成。生长因子介导的多层种植体与宿主组织的骨整合成功使骨-种植体界面强度比未涂覆的种植体提高了15倍。这些发现证明了这种分层释放策略的潜力，可以引入耐用的下一代植入物解决方案，最终向未来大型动物模型走向临床迈出了重要的一步。
Infections associated with orthopedic implants cause increased morbidity and significant healthcare cost. A prolonged and expensive two-stage procedure requiring two surgical steps and a 6–8 week period of joint immobilization exists as today’s gold standard for the revision arthroplasty of an infected prosthesis. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a continually growing part of the population. Here, we demonstrate that a single-stage revision using prostheses coated with self-assembled, hydrolytically degradable multilayers that sequentially deliver the antibiotic (gentamicin) and the osteoinductive growth factor (BMP-2) in a time-staggered manner enables both eradication of established biofilms and complete and rapid bone tissue repair around the implant in rats with induced osteomyelitis. The nanolayered construct allows precise independent control of release kinetics and loading for each therapeutic agent in an infected implant environment. Antibiotics contained in top layers can be tuned to provide a rapid release at early times sufficient to eliminate infection, followed by sustained release for several weeks, and the underlying BMP-2 component enables a long-term sustained release of BMP-2, which induced more significant and mechanically competent bone formation than a short-term burst release. The successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength 15-fold when compared with the uncoated one. These findings demonstrate the potential of this layered release strategy to introduce a durable next-generation implant solution, ultimately an important step forward to future large animal models toward the clinic.
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DOI：
10.5402/2011/290851
发表时间：
2011
期刊：
ISRN orthopedics
影响因子：
--
作者：
Bistolfi A;Massazza G;Verné E;Massè A;Deledda D;Ferraris S;Miola M;Galetto F;Crova M
通讯作者：
Crova M
影响因子：
14
作者：
Macdonald, Mara L.;Samuel, Raymond E.;Shah, Nisarg J.;Padera, Robert F.;Beben, Yvette M.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
14
作者：
Min, Jouha;Braatz, Richard D.;Hammond, Paula T.
通讯作者：
Hammond, Paula T.
影响因子：
5.3
作者：
Bozic, Kevin J.;Kurtz, Steven M.;Berry, Daniel J.
通讯作者：
Berry, Daniel J.
影响因子：
41.2
作者：
DeMuth PC;Min Y;Huang B;Kramer JA;Miller AD;Barouch DH;Hammond PT;Irvine DJ
通讯作者：
Irvine DJ