Dual-functional titanium implants via polydopamine-mediated lithium and copper co-incorporation: synergistic enhancement of osseointegration and antibacterial efficacy.

IF 4.3 3区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Frontiers in Bioengineering and Biotechnology Pub Date : 2025-05-12 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1593545
Jun Li, Bo Jiang, Liu Yang, Pu Zhang, Jingwen Wu, Yalan Yang, Yan Yang, Guiling Wang, Jie Chen, Ling Zhang, Shiqin Huang, Lingli Zhang, En Zhang
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引用次数: 0

Abstract

Introduction: Orthopedic implant failure due to inadequate osseointegration and infection remains a critical challenge. To address this, we engineered a polydopamine (PDA)-mediated dual-functional platform for lithium (Li+) and copper (Cu2+) co-incorporation on titanium alloy (Ti6Al4V) implants, aiming to synergize osteogenic and antibacterial properties through a scalable surface modification strategy.

Methods: PDA coatings were polymerized onto polished Ti64 substrates, followed by sequential immersion in LiCl (800 μM) and CuCl2 (10 μM) solutions to construct Li+/Cu2+ co-doped surfaces (PDA@Li 800-Cu 10). In vitro assays assessed MC3T3-E1 pre-osteoblast proliferation (CCK-8), osteogenic differentiation (ALP activity, RT-PCR for ALP/Axin2), and antibacterial activity against S. aureus and E. coli (live/dead staining, CFU assays). In vivo efficacy was evaluated in a rat femoral defect model via micro-CT and histology.

Results and discussion: Li+-functionalized surfaces (PDA@Li 800) enhanced osteoblast proliferation and osteogenesis via Wnt/β-catenin activation. Cu2+-loaded coatings (PDA@Cu 10) eradicated >99% bacteria but moderately suppressed osteogenic markers. The dual-doped PDA@Li 800-Cu 10 surface resolved this bioactivity conflict, maintaining antibacterial efficacy comparable to PDA@Cu 10 while elevating the osteogenic capacity of Cu2+-only modified surfaces. In vivo, dual-modified implants eliminated bacterial colonization within 72 h and significantly increased peri-implant bone volume (BV/TV) in comparison to Ti64 controls, outperforming PDA-only counterparts. By harmonizing Li-driven osteoinduction and Cu-mediated bactericidal action through a scalable PDA platform, this work advances a transformative strategy for next-generation orthopedic and dental implants, simultaneously addressing infection risks and bone regeneration demands.

多多巴胺介导的锂铜共掺入双功能钛种植体:协同增强骨整合和抗菌效果。
由于骨整合不足和感染导致的骨科种植失败仍然是一个关键的挑战。为了解决这个问题,我们设计了一个聚多巴胺(PDA)介导的双功能平台,将锂(Li+)和铜(Cu2+)共同掺入钛合金(Ti6Al4V)植入物中,旨在通过可扩展的表面改性策略协同成骨和抗菌性能。方法:将PDA涂层聚合到抛光的Ti64衬底上,然后依次浸入LiCl (800 μM)和CuCl2 (10 μM)溶液中构建Li+/Cu2+共掺杂表面(PDA@Li 800- cu 10)。体外实验评估MC3T3-E1成骨前细胞增殖(CCK-8)、成骨分化(ALP活性,RT-PCR检测ALP/Axin2)以及对金黄色葡萄球菌和大肠杆菌的抗菌活性(活/死染色,CFU测定)。在大鼠股骨缺损模型中,通过显微ct和组织学方法评价其体内疗效。结果和讨论:Li+功能化表面(PDA@Li 800)通过Wnt/β-catenin激活促进成骨细胞增殖和成骨。Cu2+负载涂层(PDA@Cu 10)根除>99%的细菌,但适度抑制成骨标志物。双掺杂PDA@Li 800-Cu 10表面解决了这种生物活性冲突,保持了与PDA@Cu 10相当的抗菌功效,同时提高了Cu2+修饰表面的成骨能力。在体内,与Ti64对照相比,双重修饰的种植体在72小时内消除了细菌定植,并显著增加了种植体周围骨体积(BV/TV),优于仅使用pda的对照。通过可扩展的PDA平台,通过协调锂驱动的骨诱导和cu介导的灭菌作用,这项工作推进了下一代骨科和牙科植入物的变革策略,同时解决了感染风险和骨再生需求。
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来源期刊
Frontiers in Bioengineering and Biotechnology
Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering
CiteScore
8.30
自引率
5.30%
发文量
2270
审稿时长
12 weeks
期刊介绍: The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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