黑磷及E7功能化磺化聚醚醚酮具有有效的成骨性和抗菌活性

王笑; 张舒凝; 朱爱; 曹玲燕; 徐龙; 王俊杰; 郑飞; 张翔凯; 陈红艳; 蒋欣泉

doi:10.1016/j.eng.2024.07.019

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工程（英文） ›› 2025, Vol. 46 ›› Issue (3) : 147-161. DOI: 10.1016/j.eng.2024.07.019

组织工程

Article

黑磷及E7功能化磺化聚醚醚酮具有有效的成骨性和抗菌活性

王笑 ^a^,^b ,
张舒凝 ^a^,^b ,
朱爱 ^b ,
曹玲燕 ^a^,^b ,
徐龙 ^c ,
王俊杰 ^b ,
郑飞 ^a^,^b ,
张翔凯 ^b ,
陈红艳 ^a^,^b^,^* ,
蒋欣泉 ^a^,^b^,^*

作者信息 +

Black Phosphorus and E7-Functionalized Sulfonated Polyetheretherketone with Effective Osteogenicity and Antibacterial Activity

Xiao Wang ^a^,^b^,^# ,
Shuning Zhang ^a^,^b^,^# ,
Ai Zhu ^b ,
Lingyan Cao ^a^,^b ,
Long Xu ^c ,
Junjie Wang ^b ,
Fei Zheng ^a^,^b ,
Xiangkai Zhang ^b ,
Hongyan Chen ^a^,^b^,^* ,
Xinquan Jiang ^a^,^b^,^*

Author information +

History +

Abstract

Given its excellent biological properties and the matching of its elastic modulus with that of human bone tissue, medical polyetheretherketone (PEEK) is considered a desirable candidate for bone-implant materials. However, its poor osseointegrative and antibacterial properties greatly limit its clinical application. To address these concerns, a functional PEEK implant is needed. Herein, a novel photo-responsive multifunctional PEEK-based implant material (sPEEK/BP/E7) with both effective osteogenesis and good disinfection properties was constructed via the self-assembly of black phosphorus (BP) nanosheets, mussel-inspired polydopamine (PDA), and bioactive short peptide E7 on sulfonated PEEK (sPEEK). The versatile micro-/nano-structured PEEK surface provides superior hydrophilicity, a favorable osteogenic microenvironment, and excellent photothermal effects under near-infrared (NIR) irradiation. The in vitro results showed that sPEEK/BP/E7 displays enhanced cytocompatibility and osteogenicity in terms of cell adhesion, proliferation, alkaline phosphatase (ALP) activity, matrix mineralization, and osteogenesis-related gene expression, superior to those of the sPEEK and sPEEK/BP samples. In addition to osteogenesis, the multifunctional coating exhibited strong antibacterial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, it was confirmed in a rat femoral infection model that sPEEK/BP/E7 effectively resisted infection caused by S. aureus under NIR light irradiation and promoted osseointegration in vivo. Thus, this work presents a facile strategy to realize improvement of the “functional integration” of new polymer bone–implant materials and provide new ideas for their clinical application.

Keywords

Polyetheretherketone / Black phosphorus nanosheets / E7 peptides / Stem cell recruitment / Osteogenesis / Antibacterial

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王笑, 张舒凝, 朱爱. 黑磷及E7功能化磺化聚醚醚酮具有有效的成骨性和抗菌活性. Engineering. 2025, 46(3): 147-161 https://doi.org/10.1016/j.eng.2024.07.019

参考文献

原文顺序 | 文献年度倒序 | 文中引用次数倒序

[1]	He M, Huang Y, Xu H, Feng G, Liu L, Li Y, et al.Modification of polyetheretherketone implants: from enhancing bone integration to enabling multi-modal therapeutics.Acta Biomater 2021; 129:18-32.
[2]	Kersten RFMR, van Gaalen SM, de Gast A, Öner FC.Polyetheretherketone (PEEK) cages in cervical applications: a systematic review.Spine J 2015; 15(6):1446-1460.
[3]	Zhao Y, Wong HM, Wang W, Li P, Xu Z, Chong EYW, et al.Cytocompatibility, osseointegration, and bioactivity of three-dimensional porous and nanostructured network on polyetheretherketone.Biomaterials 2013; 34(37):9264-9277.
[4]	Wan T, Jiao Z, Guo M, Wang Z, Wan Y, Lin K, et al.Gaseous sulfur trioxide induced controllable sulfonation promoting biomineralization and osseointegration of polyetheretherketone implants.Bioact Mater 2020; 5(4):1004-1017.
[5]	Xu X, Li Y, Wang L, Li Y, Pan J, Fu X, et al.Triple-functional polyetheretherketone surface with enhanced bacteriostasis and anti-inflammatory and osseointegrative properties for implant application.Biomaterials 2019; 212:98-114.
[6]	Wang Y, Zhang S, Nie B, Qu X, Yue B.Approaches to biofunctionalize polyetheretherketone for antibacterial: a review.Front Bioeng Biotechnol 2022; 10:895288.
[7]	Gao C, Wang Z, Jiao Z, Wu Z, Guo M, Wang Y, et al.Enhancing antibacterial capability and osseointegration of polyetheretherketone (PEEK) implants by dual-functional surface modification.Mater Des 2021; 205:109733.
[8]	Zheng Z, Liu P, Zhang X, Xin J, Wang Y, Zou X, et al.Strategies to improve bioactive and antibacterial properties of polyetheretherketone (PEEK) for use as orthopedic implants.Mater Today Bio 2022; 16:100402.
[9]	Zhang S, Long J, Chen L, Zhang J, Fan Y, Shi J, et al.Treatment methods toward improving the anti-infection ability of poly(etheretherketone) implants for medical applications.Colloids Surf B Biointerfaces 2022; 218:112769.
[10]	Wu Y, Liao Q, Wu L, Luo Y, Zhang W, Guan M, et al.ZnL₂-BPs integrated bone scaffold under sequential photothermal mediation: a win–win strategy delivering antibacterial therapy and fostering osteogenesis thereafter.ACS Nano 2021; 15(11):17854-17869.
[11]	Tan L, Li J, Liu X, Cui Z, Yang X, Zhu S, et al.Rapid biofilm eradication on bone implants using red phosphorus and near-infrared light.Adv Mater 2018; 30(31):e1801808.
[12]	Hu J, Ding Y, Tao B, Yuan Z, Yang Y, Xu K, et al.Surface modification of titanium substrate via combining photothermal therapy and quorum-sensing-inhibition strategy for improving osseointegration and treating biofilm-associated bacterial infection.Bioact Mater 2022; 18:228-241.
[13]	Tan L, Li M, Luo Z, Cai K, Hu Y.Black phosphorus biomaterials for photo-controlled bone tissue engineering.Compos Part B Eng 2022; 246:110245.
[14]	Mehrjou B, Wu Y, Liu P, Wang G, Chu PK.Design and properties of antimicrobial biomaterials surfaces.Adv Healthc Mater 2023; 12(16):e2202073.
[15]	Fu J, Liu T, Feng X, Zhou Y, Chen M, Wang W, et al.A perfect pair: stabilized black phosphorous nanosheets engineering with antimicrobial peptides for robust multidrug resistant bacteria eradication.Adv Healthc Mater 2022; 11(10):e2101846.
[16]	Wen C, Zhang Y, Lai L, Zhang X, Liu Y, Guo Q, et al.Photothermally enhanced cascaded nanozyme-functionalized black phosphorus nanosheets for targeted treatment of infected diabetic wounds.Adv Healthc Mater 2023; 2302955:e2302955.
[17]	Wu N, Wang X, Das CM, Ma M, Qiao N, Fan T, et al.Bioengineering applications of black phosphorus and their toxicity assessment.Environ Sci Nano 2021; 8(12):3452-3477.
[18]	İAksoy , Kü Hçükkeçeci, Sevgi F, Metin Ö, Hatay PI.Photothermal antibacterial and antibiofilm activity of black phosphorus/gold nanocomposites against pathogenic bacteria.ACS Appl Mater Interfaces 2020; 12(24):26822-26831.
[19]	Zeng J, Gu C, Geng X, Lin K, Xie Y, Chen X.Combined photothermal and sonodynamic therapy using a 2D black phosphorus nanosheets loaded coating for efficient bacterial inhibition and bone–implant integration.Biomaterials 2023; 297:122122.
[20]	Jing X, Xiong Z, Lin Z, Sun T.The application of black phosphorus nanomaterials in bone tissue engineering.Pharmaceutics 2022; 14(12):2634.
[21]	Li Y, Liu C, Cheng X, Wang J, Pan Y, Liu C, et al.PDA-BPs integrated mussel-inspired multifunctional hydrogel coating on PPENK implants for anti-tumor therapy, antibacterial infection and bone regeneration.Bioact Mater 2023; 27:546-559.
[22]	Zeng X, Luo M, Liu G, Wang X, Tao W, Lin Y, et al.Polydopamine-modified black phosphorous nanocapsule with enhanced stability and photothermal performance for tumor multimodal treatments.Adv Sci 2018; 5(10):1800510.
[23]	Wang G, Qian G, Yao J, Cai W, Peng S, Shuai C.Polydopamine-decorated black phosphorous to enhance stability in polymer scaffold.Nanotechnology 2021; 32(45):455701.
[24]	Wang Z, Tang Y, Wang P, Cheng Z, Chen F, Lu Y, et al.Dynamical integration of antimicrobial, anti-inflammatory, and pro-osteogenic activities on polyetheretherketone via a porous N-halamine polymeric coating.Adv Funct Mater 2023; 33(41):2307286.
[25]	Li M, Bai J, Tao H, Hao L, Yin W, Ren X, et al.Rational integration of defense and repair synergy on PEEK osteoimplants via biomimetic peptide clicking strategy.Bioact Mater 2021; 8:309-324.
[26]	He M, Wang H, Han Q, Shi X, He S, Sun J, et al.Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration.Biomaterials 2023; 303:122355.
[27]	Wang X, Pan L, Zheng A, Cao L, Wen J, Su T, et al.Multifunctionalized carbon-fiber-reinforced polyetheretherketone implant for rapid osseointegration under infected environment.Bioact Mater 2022; 24:236-250.
[28]	Wei Y, Chen M, Li M, Wang D, Cai K, Luo Z, et al.Aptamer/hydroxyapatite-functionalized titanium substrate promotes implant osseointegration via recruiting mesenchymal stem cells.ACS Appl Mater Interfaces 2022; 14(38):42915-42930.
[29]	Bai J, Ge G, Wang Q, Li W, Zheng K, Xu Y, et al.Engineering stem cell recruitment and osteoinduction via bioadhesive molecular mimics to improve osteoporotic bone–implant integration.Research 2022; 2022:9823784.
[30]	Mao Y, Chen Y, Li W, Wang Y, Qiu J, Fu Y, et al.Physiology-inspired multilayer nanofibrous membranes modulating endogenous stem cell recruitment and osteo-differentiation for staged bone regeneration.Adv Healthc Mater 2022; 11(21):e2201457.
[31]	Li L, Lu H, Zhao Y, Luo J, Yang L, Liu W, et al.Functionalized cell-free scaffolds for bone defect repair inspired by self-healing of bone fractures: a review and new perspectives.Mater Sci Eng C 2019; 98:1241-1251.
[32]	Xu X, Xu H, Chai Q, Li Z, Man Z, Li W.Novel functionalized Ti6Al4V scaffold for preventing infection and promoting rapid osseointegration.Mater Des 2023; 226:111612.
[33]	Shao Z, Zhang X, Pi Y, Wang X, Jia Z, Zhu J, et al.Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo.Biomaterials 2012; 33(12):3375-3387.
[34]	Shi W, Wu J, Pi Y, Yan X, Hu X, Cheng J, et al.E7 peptide enables BMSC adhesion and promotes chondrogenic differentiation of BMSCs via the LncRNA H19/miR675 axis.Bioengineering 2023; 10(7):781.
[35]	Zhang W, Sun T, Zhang J, Hu X, Yang M, Han L, et al.Construction of artificial periosteum with methacrylamide gelatin hydrogel-Wharton’s jelly based on stem cell recruitment and its application in bone tissue engineering.Mater Today Bio 2022; 18:100528.
[36]	Wu J, Cao L, Liu Y, Zheng A, Jiao D, Zeng D, et al.Functionalization of silk fibroin electrospun scaffolds via BMSC affinity peptide grafting through oxidative self-polymerization of dopamine for bone regeneration.ACS Appl Mater Interfaces 2019; 11(9):8878-8895.
[37]	Ouyang L, Zhao Y, Jin G, Lu T, Li J, Qiao Y, et al.Influence of sulfur content on bone formation and antibacterial ability of sulfonated PEEK.Biomaterials 2016; 83:115-126.
[38]	Zhou L, Guo P, D M’Este, Tong W, Xu J, Yao H, et al.Functionalized hydrogels for articular cartilage tissue engineering.Engineering 2022; 13:71-90.
[39]	Qin W, Xing T, Ma J, Tang B, Chen W.Decoration with electronegative 2D materials based on chemical transition layers on CFR-PEEK implants for promoting osteogenesis.J Mech Behav Biomed Mater 2024; 152:106436.
[40]	Pacelli S, Basu S, Whitlow J, Chakravarti A, Acosta F, Varshney A, et al.Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration.Adv Drug Deliv Rev 2017; 120:50-70.
[41]	Wu J, Liu Y, Cao Q, Yu T, Zhang J, Liu Q, et al.Growth factors enhanced angiogenesis and osteogenesis on polydopamine coated titanium surface for bone regeneration.Mater Des 2020; 196:109162.
[42]	Gentleman MM, Gentleman E.The role of surface free energy in osteoblast–biomaterial interactions.Int Mater Rev 2014; 59(8):417-429.
[43]	Su P, Tian Y, Yang C, Ma X, Wang X, Pei J, et al.Mesenchymal stem cell migration during bone formation and bone diseases therapy.Int J Mol Sci 2018; 19(8):2343.
[44]	Zhou L, Xu J, Schwab A, Tong W, Xu J, Zheng L, et al.Engineered biochemical cues of regenerative biomaterials to enhance endogenous stem/progenitor cells (ESPCs)-mediated articular cartilage repair.Bioact Mater 2023; 26:490-512.
[45]	Yuan B, Zhou X, Li Y, Zhao Y, Xue M, Guo Q, et al.Black-phosphorus-nanosheet-reinforced coating of implants for sequential biofilm ablation and bone fracture healing acceleration.ACS Appl Mater Interfaces 2022; 14(41):47036-47051.
[46]	Zhang W, Cao H, Zhang X, Li G, Chang Q, Zhao J, et al.A strontium-incorporated nanoporous titanium implant surface for rapid osseointegration.Nanoscale 2016; 8(9):5291-5301.
[47]	Zhou L, Gjvm VO, Malda J, Stoddart MJ, Lai Y, Richards RG, et al.Innovative tissue-engineered strategies for osteochondral defect repair and regeneration: current progress and challenges.Adv Healthc Mater 2020; 9(23):e2001008.
[48]	Goldring CEP, Duffy PA, Benvenisty N, Andrews PW, Ben-David U, Eakins R, et al.Assessing the safety of stem cell therapeutics.Cell Stem Cell 2011; 8(6):618-628.
[49]	Marom R, Shur I, Solomon R, Benayahu D.Characterization of adhesion and differentiation markers of osteogenic marrow stromal cells.J Cell Physiol 2005; 202(1):41-48.
[50]	Ge Q, Wang X, Luo Y, Zheng X, Ma L.E7-Modified substrates to promote adhesion and maintain stemness of mesenchymal stem cells.Macromol Biosci 2021; 21(4):e2000384.
[51]	Ramaraju H, Miller SJ, Kohn DH.Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials.Biomaterials 2017; 134:1-12.
[52]	Amarasekara DS, Kim S, Rho J.Regulation of osteoblast differentiation by cytokine networks.Int J Mol Sci 2021; 22(6):2851.
[53]	Lee JS, Lee JM, Im GI.Electroporation-mediated transfer of Runx2 and Osterix genes to enhance osteogenesis of adipose stem cells.Biomaterials 2011; 32(3):760-768.
[54]	Li W, Xu H, Han X, Sun S, Chai Q, Xu X, et al.Simultaneously promoting adhesion and osteogenic differentiation of bone marrow-derived mesenchymal cells by a functional electrospun scaffold.Colloids Surf B Biointerfaces 2020; 192:111040.
[55]	Jia Z, Xiu P, Li M, Xu X, Shi Y, Cheng Y, et al.Bioinspired anchoring AgNPs onto micro-nanoporous TiO₂ orthopedic coatings: trap-killing of bacteria, surface-regulated osteoblast functions and host responses.Biomaterials 2016; 75:203-222.
[56]	Huo J, Jia Q, Huang H, Zhang J, Li P, Dong X, et al.Emerging photothermal-derived multimodal synergistic therapy in combating bacterial infections.Chem Soc Rev 2021; 50(15):8762-8789.