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Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy

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Bioactive Materials 2021年第1期6卷 146-157页

作者： Yu Liu Jiacheng Du Peng Peng Ruoyu Cheng Jiayi Lin Congxin Xu Huilin Yang Wenguo Cui Haiqing Mao Yuling Li dechun geng Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu215006PR China Shanghai Institute of Traumatology and Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin Second RoadShanghai200025PR China Department of Orthopaedics Affiliated Hospital of North Sichuan Medical CollegeNo.63 Wenhua RoadNanchongSichuan637000PR China

Surgery is the final choice for most patients with intervertebral disc degeneration(IDD).Operation-caused trauma will cause inflammation in the intervertebral *** inflammation will cause tissue defects and induce tissue degeneration,IDD recurrence and the occurrence of other ***,we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin(ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local ***-liposomes(ASP-Lips)were incorporated into a photocrosslinkable gelatin-methacryloyl(GelMA)via *** material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1(HMGB1)from the nucleus to the *** further assessed the expression of inflammatory cytokines,such as interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α),and degeneration-related factors,such as type II collagen(COL-2),Aggrecan,matrix metallopeptidases-3(MMP-3),MMP-13,a disintegrin and metalloproteinase with thrombospondin motifs-4(ADAMTS-4)and ADAMTS-5 in rat nucleus pulpous *** level of IDD was analyzed through H&E,safranin-O staining and immunohistochemistry in rabbit *** vitro,we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines,MMP-3 and-13,and ADAMTS-4 and-5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the *** vivo,ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue *** composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.

关键词： Composite hydrogel Intervertebral disc degeneration Recurrence Inflammation Aspirin

Punicalagin ameliorates collagen-induced arthritis by downregulating M1 macrophage and pyroptosis via NF-κB signaling pathway

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Science China(Life Sciences) 2022年第3期65卷 588-603页

作者： Gaoran Ge Jiaxiang Bai Qing Wang Xiaolong Liang Huaqiang Tao Hao Chen Minggang Wei Junjie Niu Huilin Yang Yaozeng Xu Yuefeng Hao Yi Xue dechun geng Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Traditional Chinese Medicine The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Orthopaedics and Sports Medicine Center Suzhou Municipal Hospital(North District)Nanjing Medical University Affiliated Suzhou HospitalSuzhou 215006China Department of Orthopaedics Changshu Hospital Affiliated to Nanjing University of Traditional Chinese MedicineSuzhou 215500China

Rheumatoid arthritis(RA)is a chronic inflammatory disease that eventually leads to *** cell infiltration,severe joint breaking and systemic bone loss are the main clinical *** this study,we established a collagen-induced arthritis(CIA)model and found a large number of M1 macrophages and pyroptosis,which are important sources of proinflammatory ***(PUN)is an active substance extracted from pomegranate *** found that it inhibited joint inflammation,cartilage damage and systemic bone destruction in CIA *** effectively alleviated the high expression of inflammatory cytokines in synovial tissue in *** treatment shifted macrophages from the M1 phenotype to the M2 phenotype after stimulation with lipopolysaccharide(LPS)and interferon(IFN)-γ.The expression of inducible nitric oxide synthase(i NOS)and other proinflammatory cytokines released by M1 macrophages was decreased in the PUN treatment ***,simultaneously,the expression of markers of anti-inflammatory M2 macrophages,such as arginase(Arg)-1 and interleukin(IL)-10,was *** addition,PUN treatment attenuated pyroptosis by downregulating the expression of NLRP3 and caspase-1,thereby preventing inflammatory cell death resulting from the release of IL-1βand ***,PUN inhibited the activation of receptor activators of the nuclear factor-κB(NF-κB)signaling pathway,which contributes to M1 polarization and pyroptosis of *** concluded that PUN ameliorated pathological inflammation by inhibiting M1 phenotype polarization and pyroptosis and has great potential as a therapeutic treatment for human RA.

关键词： rheumatoid arthritis pomegranate M1 macrophage pyroptosis

A programmed surface on polyetheretherketone for sequentially dictating osteoimmunomodulation and bone regeneration to achieve ameliorative osseointegration under osteoporotic conditions

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Bioactive Materials 2022年第8期7卷 364-376页

作者： Yanyan Zheng Ang Gao Jiaxiang Bai Qing Liao Yuzheng Wu Wei Zhang Min Guan Liping Tong dechun geng Xin Zhao Paul K.Chu Huaiyu Wang Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055China School of Basic Medical Sciences and Forensic Medicine North Sichuan Medical CollegeNanchong637000China Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhou215006China Department of Physics Department of Materials Science and EngineeringDepartment of Biomedical EngineeringCity University of Hong KongTat Chee AvenueKowloonHong KongChina Technical Institute of Physics and Chemistry Chinese Academy of SciencesBeijing100190China Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHong KongChina

Polyetheretherketone(PEEK)is a desirable alternative to conventional biomedical metals for orthopedic implants due to the excellent mechanical ***,the inherent bioinertness of PEEK contributes to inferior osseointegration of PEEK implants,especially under pathological conditions of ***,a programmed surface is designed and fabricated on PEEK to dictate osteoimmunomodulation and bone regeneration sequentially.A degradable hybrid coating consisting of poly(lactide-co-glycolide)and alendronate(ALN)loaded nano-hydroxyapatite is deposited on PEEK and then interleukin-4(IL-4)is grafted onto the outer surface of the hybrid coating with the aid of N_(2) plasma immersion ion implantation and subsequent immersion in IL-4 *** release of IL-4 together with ALN and Ca^(2+) during the first few days synergistically mitigates the early acute inflammatory reactions and creates an osteoimmunomodulatory microenvironment that facilitates bone ***,slow and sustained delivery of ALN and Ca^(2+) in the following weeks boosts osteogenesis and suppresses osteoclastogenesis simultaneously,consequently ameliorating bone-implant osseointegration even under osteoporotic *** taking into account the different phases in bone repair,this strategy of constructing advanced bone implants with sequential functions provides customizable and clinically viable therapy to osteoporotic patients.

关键词： Polyetheretherketone Surface modification Osteoimmunomodulation Sequential release Osteoporosis Osseointegration

Protective effects of sirtuin 3 on titanium particle-induced osteogenic inhibition by regulating the NLRP3 inflammasome via the GSK-3β/β-catenin signalling pathway

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Bioactive Materials 2021年第10期6卷 3343-3357页

作者： Kai Zheng Jiaxiang Bai Ning Li Meng Li Houyi Sun Weicheng Zhang Gaoran Ge Xiaolong Liang Huaqiang Tao Yi Xue Yuefeng Hao Chen Zhu Yaozeng Xu dechun geng Department of Orthopaedics The First Affiliated Hospital of Soochow UniversityNo.188 Shizi StreetSuzhouJiangsu215006PR China Department of Orthopaedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaLujiang Road No.17HefeiAnhui230001PR China Jiangsu Key Laboratory of Clinical Immunology Soochow UniversityNo.708 Renmin RoadSuzhouJiangsu215007PR China Department of Orthopaedics Changshu Hospital Affiliated to Nanjing University of Traditional Chinese MedicineSuzhouJiangsu215500PR China Orthopaedics and Sports Medicine Center Suzhou Municipal Hospital(North District)Nanjing Medical University Affiliated Suzhou HospitalNo.242 Guangji RoadSuzhou215006PR China

Periprosthetic osteolysis(PPO)remains the key factor in implant failure and subsequent revision surgery and is mainly triggered by wear *** studies have shown that inhibition of osteoblastic differentiation is the most widespread incident affecting the interface of trabecular and loosening ***,the NLRP3 inflammasome is activated by prosthetic ***3,an NAD+-dependent deacetylase of mitochondria,regulates the function of mitochondria in diverse ***,whether SIRT3 can mitigate wear debris-induced osteolysis by inhibiting the NLRP3 inflammasome and enhancing osteogenesis has not been previously ***,we investigated the role of SIRT3 during the process of titanium(Ti)particle-induced *** revealed that upregulated SIRT3 dramatically attenuated Ti particle-induced osteogenic inhibition through suppression of the NLRP3 inflammasome and improvement of osteogenesis in vivo and in ***,we found that SIRT3 interference in the process of Ti particle-induced osteolysis relied on the GSK-3β/β-catenin signalling ***,these findings indicated that SIRT3 may serve as a rational new treatment against debris-induced PPO by deacetylase-dependent inflammasome attenuation.

关键词： SIRT3 Titanium particles Periprosthetic osteolysis NLRP3 inflammasome Osteoblast

Rational integration of defense and repair synergy on PEEK osteoimplants via biomimetic peptide clicking strategy

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Bioactive Materials 2022年第2期7卷 309-324页

作者： Meng Li Jiaxiang Bai Huaqiang Tao Li Hao Weiling Yin Xiaoxue Ren Ang Gao Ning Li Miao Wang Shiyuan Fang Yaozeng Xu Liang Chen Huilin Yang Huaiyu Wang Guoqing Pan dechun geng Department of Orthopaedics The First Affiliated Hospital of Soochow University188 Shizi StreetSuzhou215006JiangsuChina Institute for Advanced Materials School of Materials Science and EngineeringJiangsu University301 Xuefu RoadZhenjiang212013JiangsuChina Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055GuangdongChina Department of Orthopaedics The First Affiliated Hospital of USTCUniversity of Science and Technology of China17 Lujiang RoadHefei230001AnhuiChina Department of Oncology The First Affiliated Hospital of USTCUniversity of Science and Technology of China17 Lujiang RoadHefei230001AnhuiChina

Polyetheretherketone(PEEK)has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical ***,its biological inertness,poor osteoinduction,and weak antibacterial activity make the clinical applications in a *** by the mussel adhesion mechanism,here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins(Mfps)-mimic peptide with clickable azido *** peptide enables mussel-like adhesion on PEEK biomaterial surfaces,leaving azido groups for the further steps of *** this study,antimicrobial peptide(AMP)and osteogenic growth peptide(OGP)were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue *** bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios,an optimal PEEK surface was finally obtained in this research,which could long-term inhibit bacterial growth,stabilize bone homeostasis and facilitate interfacial bone *** a word,this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants,in particular,achieving rational integration of multiple biofunctions to match clinical requirements.

关键词： Surface biomodification Polyetheretherketone Anti-infectivity and osteo-inductivity Mussel adhesion Bioorthogonal chemistry

水甘草碱抑制破骨细胞活化缓解磨损颗粒诱导的炎性骨溶解

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中国组织工程研究 2024年第10期28卷 1519-1525页

作者：张巍俞磊杨鹏耿德春苏州大学附属第一医院骨科江苏省苏州市215006

背景:水甘草碱因其抗炎生物活性在心肌重塑、急性肾损伤和肺损伤等疾病中表现出良好的治疗作用。假体磨损颗粒常引发无菌性炎症,炎性因子的大量释放进一步导致了假体周围骨质的破坏和骨量丢失,然而目前尚无水甘草碱对假体周围骨溶解确... 详细信息

背景:水甘草碱因其抗炎生物活性在心肌重塑、急性肾损伤和肺损伤等疾病中表现出良好的治疗作用。假体磨损颗粒常引发无菌性炎症,炎性因子的大量释放进一步导致了假体周围骨质的破坏和骨量丢失,然而目前尚无水甘草碱对假体周围骨溶解确切疗效的基础研究。目的:探讨水甘草碱对破骨细胞活化、炎症因子表达及磨损颗粒诱导炎性骨溶解的影响。方法:①细胞实验:将RAW264.7细胞分4组培养:对照组细胞加入完全培养基;破骨诱导组加入破骨诱导培养基(含50 ng/mL RANKL的完全培养基);水甘草碱低、高剂量组分别加入1,5μmol/L水甘草碱处理4 h后加入破骨诱导培养基。破骨诱导5 d后,分别进行抗酒石酸酸性磷酸酶染色、F-actin染色及RT-PCR检测。②动物实验:采用随机数字表法将20只C57BL/6J小鼠随机分为假手术组、骨溶解组、水甘草碱低及高剂量组,每组5只。骨溶解组、水甘草碱低及高剂量组通过将钛颗粒注射至颅骨表面的方法建立颅骨骨溶解模型,造模后第2天,水甘草碱低、高剂量组分别腹腔注射10,20 mg/kg水甘草碱,每隔1 d注射1次,直至造模2周后,收集小鼠动脉血血清进行炎性因子(白细胞介素1β、白细胞介素6、肿瘤坏死因子α)检测,收集颅骨进行micro-CT扫描和骨参数分析。结果与结论:①细胞实验:抗酒石酸酸性磷酸酶和F-actin染色显示,与破骨诱导组比较,水甘草碱低、高剂量组可抑制破骨细胞的活化及骨吸收,其中以高剂量组抑制更显著。RT-PCR检测结果显示,与对照组比较,破骨诱导组3种炎症因子的mRNA表达升高(P<0.01);与破骨诱导组比较,水甘草碱低及高剂量组3种炎症因子的mRNA表达降低(P<0.01),其中以高剂量组降低更明显。②动物实验:与假手术组比较,骨溶解组3种炎性因子水平升高(P<0.01);与骨溶解组比较,水甘草碱低及高剂量组3种炎性因子水平降低(P<0.05,P<0.01),其中以高剂量组降低更明显。micro-CT扫描结果显示,钛颗粒导致小鼠颅骨骨溶解破坏,水甘草碱可抑制钛颗粒诱导的骨溶解,其中以高剂量组抑制作用更显著。③结果表明:水甘草碱可通过抑制炎症因子释放下调破骨细胞的骨吸收功能来改善钛颗粒诱导的骨溶解、骨破坏。

关键词：水甘草碱炎性因子破骨细胞活化磨损颗粒假体周围骨溶解

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假体周围骨溶解中的新型细胞程序性死亡

中国组织工程研究 2024年第21期28卷 3393-3399页

作者：梁晓龙郑恺耿德春徐耀增苏州大学附属第一医院骨科江苏省苏州市215008

背景:最近的研究发现,在假体周围骨溶解中还发现了除凋亡外的新型细胞程序性死亡途径,参与了局部慢性炎症的调节以及成骨细胞和破骨细胞病理条件下的转归,对假体周围骨溶解的治疗和预后有着重要价值。目的:通过总结有关新型细胞程序性... 详细信息

背景:最近的研究发现,在假体周围骨溶解中还发现了除凋亡外的新型细胞程序性死亡途径,参与了局部慢性炎症的调节以及成骨细胞和破骨细胞病理条件下的转归,对假体周围骨溶解的治疗和预后有着重要价值。目的:通过总结有关新型细胞程序性死亡的研究,为防治假体周围骨质溶解提供新的思路和策略。方法:由第一作者应用计算机检索2005-2022年出版的文献,以“磨损颗粒,假体周围骨溶解,细胞程序性死亡,凋亡,自噬,焦亡,坏死性凋亡,铁死亡”等为中文检索词检索中国知网、万方和维普数据库;以“osteolysis,wear debris,wear particles,peri*prosthetic osteolysis,PPOL,aseptic loosening,autophagy,regulated cell death,programmed cell death,apoptosis,pyroptosis,autophagic cell death,autophagy,necroptosis,ferroptosis”等为英文检索词检索PubMed和Web of Science数据库,按照入选标准最终共纳入68篇文章。结果与结论:①自噬不足或过度激活都将引起细胞死亡,抑制成骨功能并促进破骨功能,引起骨代谢紊乱和骨溶解;②焦亡在假体周围骨溶解中的研究近年来备受关注,NOD样受体蛋白3炎性小体在局部炎症中扮演着重要角色,抑制焦亡可有效缓解骨溶解;③坏死性凋亡在体外已被证明可以抑制成骨细胞和破骨细胞的形成和功能,从而影响骨吸收和骨破坏过程;④铁死亡作为一种最新发现的细胞程序性死亡方式,受到复杂的信号通路和机制调控,目前尚未完全阐明;⑤自噬、焦亡、坏死性凋亡及铁死亡在假体周围骨溶解的发生发展中具有重要作用,其相关信号通路、基因等仍需要更深入的研究。

关键词：磨损颗粒假体周围骨溶解细胞程序性死亡自噬焦亡坏死性凋亡铁死亡综述

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关节镜治疗老年巨大肩袖撕裂的疗效分析

中华医学杂志 2017年第15期97卷 1145-1149页

作者：沈继何耀华耿德春蒋定华徐耀增苏州大学附属第一医院骨科江苏215006 上海交通大学附属第六人民医院骨科

目的探讨应用关节镜技术治疗老年巨大肩袖撕裂病人的手术方法。方法2012年6月至2015年6月苏州大学附属第一医院骨科和上海交通大学附属第六人民医院骨科对36例老年巨大肩袖撕裂患者应用关节镜技术缝合修补，术前检测疼痛视觉模拟评分（... 详细信息

目的探讨应用关节镜技术治疗老年巨大肩袖撕裂病人的手术方法。方法2012年6月至2015年6月苏州大学附属第一医院骨科和上海交通大学附属第六人民医院骨科对36例老年巨大肩袖撕裂患者应用关节镜技术缝合修补，术前检测疼痛视觉模拟评分（VAS评分）、美国加利福尼亚大学洛杉矶分校（UCLA）评分、Constant评分和美国肩肘外科协会评分（ASES评分）以及关节活动度并随访观察治疗效果。结果巨大肩袖撕裂患者36例均得到1年以上的完全随访，平均随访时间18．5（12-30）个月。VAS、UCLA、Constant--Murley、ASES评分分别为（6．1±2．2）、（10．6±4．3）、（40．3±10．5）、（28．8±18．5）分。术前的肩关节活动度平均前屈、外展、外旋和内旋分别为（76．5±42．6）、（72．4±35．2）、（26．6±22．2）、（20．2±6．2）°。至术后1年期的随访时，VAS、UCLA、Constant、ASES评分分别改善为（1．4±1．2）、（30．4±5．2）、（82．6±12．6）、（78．8±22．6）分。肩关节活动度分别改善为前屈（152．8±25．6）°、外展（120．6±32．8）°、外旋（42．6±16．2）°、内旋（38．4±5．6）°，P〈0．05。结论关节镜方法可以有效治疗大多数老年巨大肩袖撕裂，能改善肩关节功，具有一定的临床应用价值。

关键词：肩关节关节镜检查撕裂伤肩袖

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经皮加压钢板治疗中青年股骨颈骨折疗效分析

中国修复重建外科杂志 2022年第6期36卷 708-713页

作者：汪天豪李荣群周军徐明耿德春徐耀增朱锋苏州大学附属第一医院骨科江苏苏州215008

目的探讨经皮加压钢板(percutaneous compression plate,PCCP)治疗中青年股骨颈骨折的疗效。方法回顾分析2011年1月—2019年3月采用PCCP内固定治疗且符合选择标准的173例中青年股骨颈骨折患者资料。其中男102例,女71例;年龄18~59岁,平... 详细信息

目的探讨经皮加压钢板(percutaneous compression plate,PCCP)治疗中青年股骨颈骨折的疗效。方法回顾分析2011年1月—2019年3月采用PCCP内固定治疗且符合选择标准的173例中青年股骨颈骨折患者资料。其中男102例,女71例;年龄18~59岁,平均44.9岁。致伤原因:摔伤112例,交通事故伤32例,高处坠落伤21例,击打伤7例,扭伤1例。骨折按Garden分型:无移位型90例(Ⅰ型51例、Ⅱ型39例),移位型83例(Ⅲ型57例、Ⅳ型26例);按Pauwels分型:Ⅰ型10例,Ⅱ型88例,Ⅲ型75例。受伤至手术时间1~14 d,平均4.5 d。记录手术时间、术中出血量、围术期输血情况及住院时间;术后1 d通过Garden对线指数判断骨折复位质量;观察骨折愈合情况及并发症发生情况,末次随访时采用Harris评分评价疗效。结果手术时间34~130 min,平均78.6 min;术中出血量10~250 mL,平均93.2 mL;171例围术期未输血,2例分别输血400 mL和800 mL;住院时间3~19 d,平均11.3 d。173例均获随访,随访时间11~103个月,平均42.6个月。术后X线片复查示复位质量满意170例,不满意3例。术后发生股骨头坏死13例、螺钉切出1例、退钉2例、股骨颈短缩5例,未发生需手术介入治疗的下肢深静脉血栓形成。172例患者骨折愈合,愈合时间3.0~7.5个月,平均3.6个月;1例骨折不愈合。51例患者于骨折愈合后取出内固定物。末次随访时Harris评分达优156例、良11例、可3例、差3例,优良率96.5%。结论 PCCP治疗中青年股骨颈骨折具有固定牢固、允许早期负重的优势,并有滑动加压功能,明显减少了骨不连和股骨头坏死的发生。

关键词：股骨颈骨折经皮加压钢板内固定中青年