Infected bone defects are characterised by inadequate local blood supply and the formation of bacterial biofilms, which impede bone tissue regeneration and repair, presenting a significant clinical challenge. In this study, we developed a bifunctional scaffold combining near-infrared (NIR)-responsive antibacterial activity with osteogenic properties by co-electrospinning photothermally active copper hydroxyphosphate (Cu2(OH)PO4, CuHP) and osteogenic magnesium-calcium phosphate (Mg-CaP) into poly (L-lactic acid) (PLLA) membranes. Near-infrared (NIR) irradiation activates the photothermal response of CuHP in nanofiber membrane scaffolds, effectively killing bacteria through photothermal therapy (PTT), while the released Mg-CaP synergistically promotes osteogenesis. Animal studies have revealed that the scaffold effectively inhibit infections while accelerating bone healing, offering a promising strategy for infected bone defects.
LaiXHuangJHuangS, et al.Antibacterial and osteogenic dual-functional micronano composite scaffold fabricated via melt electrowriting and solution electrospinning for bone tissue engineering. ACS Appl Mater Interfaces2024; 16(29): 37707–37721.
2.
InoueSFujikawaKMatsuki-FukushimaM, et al.Repair processes of flat bones formed via intramembranous versus endochondral ossification. J Oral Biosci2020; 62(1): 52–57.
3.
WinklerH. Treatment of chronic orthopaedic infection. EFORT Open Rev2017; 2(5): 110–116.
4.
KhanNAslanHBüttnerH, et al.The giant staphylococcal protein Embp facilitates colonization of surfaces through Velcro-like attachment to fibrillated fibronectin. eLife2022; 11: e76164.
5.
ThomasMVPuleoDA. Infection, inflammation, and bone regeneration: a paradoxical relationship. J Dent Res2011; 90(9): 1052–1061.
6.
Cámara-TorresMDuarteSSinhaR, et al.3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration. Bioact Mater2020; 6(4): 1073–1082.
7.
DiefenbeckMSchraderCGrasF, et al.Gentamicin coating of plasma chemical oxidized titanium alloy prevents implant-related osteomyelitis in rats. Biomaterials2016; 101: 156–164.
8.
MeiZGaoDHuD, et al.Activatable NIR-II photoacoustic imaging and photochemical synergistic therapy of MRSA infections using miniature Au/Ag nanorods. Biomaterials2020; 251: 120092.
9.
YuYLiPZhuC, et al.Multifunctional and recyclable photothermally responsive cryogels as efficient platforms for wound healing. Adv Funct Mater2019; 29: 1904402.
10.
WangJLiuQGuoZ, et al.Progress on biomimetic mineralization and materials for hard tissue regeneration. ACS Biomater Sci Eng2023; 9(4): 1757–1773.
11.
MuXLuYWuF, et al.Supramolecular nanodiscs self-assembled from non-ionic heptamethine cyanine for imaging-guided cancer photothermal therapy. Adv Mater2020; 32(2): e1906711.
12.
ZhangXChengGXingX, et al.Near-infrared light-triggered porous AuPd alloy nanoparticles to produce mild localized heat to accelerate bone regeneration. J Phys Chem Lett2019; 10(15): 4185–4191.
13.
TongLLiaoQZhaoY, et al.Near-infrared light control of bone regeneration with biodegradable photothermal osteoimplant. Biomaterials2019; 193: 1–11.
14.
LiuYXiaoYCaoY, et al.Construction of chitosan-based hydrogel incorporated with antimonene nanosheets for rapid capture and elimination of bacteria. Adv Funct Mater2020; 30: 2003196.
15.
TanLLiJLiuX, et al.Rapid biofilm eradication on bone implants using red phosphorus and near-infrared light. Adv Mater2018; 30(31): e1801808.
16.
GuoWQiuZGuoC, et al.Multifunctional theranostic agent of Cu2(OH)PO4 quantum dots for photoacoustic image-guided photothermal/photodynamic combination cancer therapy. ACS Appl Mater Interfaces2017; 9(11): 9348–9358.
17.
ZhangJMaXLinD, et al.Magnesium modification of a calcium phosphate cement alters bone marrow stromal cell behavior via an integrin-mediated mechanism. Biomaterials2015; 53: 251–264.
18.
WangMYuYDaiK, et al.Improved osteogenesis and angiogenesis of magnesium-doped calcium phosphate cement via macrophage immunomodulation. Biomater Sci2016; 4(11): 1574–1583.
19.
RameshBCherianKMFakoyaAOJ. Fabrication and electrospinning of 3D biodegradable poly-l-lactic acid (PLLA) nanofibers for clinical application. Methods Mol Biol2020; 2125: 119–128.
20.
XiaoGYinHXuW, et al.Modification and cytocompatibility of biocomposited porous PLLA/HA-microspheres scaffolds. J Biomater Sci Polym Ed2016; 27(14): 1462–1475.
21.
HaradaHAkayamaKKuboiR, et al.Surgical stabilization of traumatic multiple rib fractures using absorbable osteosynthesis agent (u-HA/PLLA composite material). Kyobu Geka2024; 77: 279–283.
22.
ISO 10993-12. Biological evaluation of medical devices: sample preparation and reference materials. International Organization for Standardization, 2021.
23.
JohnsonCTGarcíaAJ. Scaffold-based anti-infection strategies in bone repair. Ann Biomed Eng2015; 43(3): 515–528.
24.
DengXYuCZhangX, et al.A chitosan-coated PCL/nano-hydroxyapatite aerogel integrated with a nanofiber membrane for providing antibacterial activity and guiding bone regeneration. Nanoscale2024; 16(20): 9861–9874.
25.
UllahIHussainZUllahS, et al.An osteogenic, antibacterial, and anti-inflammatory nanocomposite hydrogel platform to accelerate bone reconstruction. J Mater Chem B2023; 11(25): 5830–5845.
26.
WangXLiBZhangC. Preparation of BMP-2/chitosan/hydroxyapatite antibacterial bio-composite coatings on titanium surfaces for bone tissue engineering. Biomed Microdevices2019; 21(4): 89.
27.
OhEJOhSHLeeIS, et al.Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis. J Biomater Appl2016; 30(10): 1534–1544.
28.
EgawaSHiraiKMatsumotoR, et al.Efficacy of antibiotic-loaded hydroxyapatite/collagen composites is dependent on adsorbability for treating Staphylococcus aureus osteomyelitis in rats. J Orthop Res2020; 38(4): 843–851.
PanHWeiYZengC, et al.Hierarchically assembled nanofiber scaffold guides long bone regeneration by promoting osteogenic/chondrogenic differentiation of endogenous mesenchymal stem cells. Small2024; 20(26): e2309868.
31.
WangCTaoHChengL, et al.Near-infrared light induced in vivo photodynamic therapy of cancer based on upconversion nanoparticles. Biomaterials2011; 32(26): 6145–6154.
32.
ZhangGYangYShiJ, et al.Near-infrared light II - assisted rapid biofilm elimination platform for bone implants at mild temperature. Biomaterials2021; 269: 120634.
33.
WangGHuangBMaX, et al.Cu2(OH)PO4, a near-infrared-activated photocatalyst. Angew Chem2013; 52(18): 4810–4813.
34.
BjarnsholtTCiofuOMolinS, et al.Applying insights from biofilm biology to drug development - can a new approach be developed?Nat Rev Drug Discov2013; 12(10): 791–808.
35.
SeebachEKubatzkyKF. Chronic implant-related bone infections-can immune modulation be a therapeutic strategy?Front Immunol2019; 10: 1724.
36.
Loc-CarrilloCWangCCandenA, et al.Local intramedullary delivery of vancomycin can prevent the development of long bone Staphylococcus aureus infection. PLoS One2016; 11(7): e0160187.
37.
Hassani BesheliNDamooghSZafarB, et al.Preparation of a codelivery system based on vancomycin/silk scaffold containing silk nanoparticle loaded VEGF. ACS Biomater Sci Eng2018; 4(8): 2836–2846.
38.
WangDLiuYLiuY, et al.A dual functional bone-defect-filling material with sequential antibacterial and osteoinductive properties for infected bone defect repair. J Biomed Mater Res2019; 107(10): 2360–2370.
39.
YangXWangQZhangY, et al.A dual-functional PEEK implant coating for anti-bacterial and accelerated osseointegration. Colloids Surf B Biointerfaces2023; 224: 113196.
40.
FangBQiuPXiaC, et al.Extracellular matrix scaffold crosslinked with vancomycin for multifunctional antibacterial bone infection therapy. Biomaterials2021; 268: 120603.
41.
YangFShiZHuY, et al.Nanohybrid hydrogel with dual functions: controlled low-temperature photothermal antibacterial activity and promoted regeneration for treating MRSA-infected bone defects. Adv Healthcare Mater2025; 14(11): e2500092.
42.
ChenCGaoYQiaoX, et al.Functional amyloid phenol-soluble modulin α1-targeting photothermal nanoplatform for effective elimination of biofilm-associated infections. ACS Nano2025; 19(22): 20613–20632.
43.
XuJWuDGeB, et al.Selective laser melting of the porous Ta scaffold with Mg-doped calcium phosphate coating for orthopedic applications. ACS Biomater Sci Eng2024; 10(3): 1435–1447.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
