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Hematoma-like dynamic hydrogelation through natural glycopeptide molecular recognition for infected bone fracture repair

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Bioactive Materials 2023年第12期30卷 73-84页

作者： Shenghao Wang Wenbo He Huan Wang Dachuan Liu Miao Wang Huilin Yang guoqing pan Bin Li Orthopedic Institute Department of Orthopaedic SurgeryMedical 3D Printing CenterThe First Affiliated HospitalSchool of Biology&Basic Medical SciencesSuzhouMedical CollegeSoochow UniversitySuzhouJiangsu215006China Collaborative Innovation Center of Hematology Soochow UniversitySuzhouJiangsu215006China Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiangJiangsu212013China

Infected bone fractures remain a major clinical challenge for orthopedic surgeons.From a tissue regeneration perspective,biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired,while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research.Hematoma,the gel-like blood coagulum,plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing.In light of this,we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study.The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin(Van)and its target dipeptide D-Ala-D-Ala(AA),which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide(OGP).In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria,improve bone regeneration and restore the local inflammatory microenvironment.Together,findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.

关键词： Dynamic biomaterial Molecular recognition Hematoma mimicking Infected fracture repair Inflammatory microenvironment restoration

Rational multivalency construction enables bactericidal effect amplification and dynamic biomaterial design

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The Innovation 2023年第5期4卷 59-68页

作者： Xu Chen Xinrui Li Wenbo He Miao Wang Ang Gao Liping Tong Shun Guo Huaiyu Wang guoqing pan Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiang 212013China Institute of Biomedicine and Biotechnology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix(ECM)-mimicking biomaterials.However,designing controllable multivalency construction strategies is still challenging.Herein,we synthesized a series of well-defined multivalent antimicrobial peptide polymers(mAMPs)by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer polymerization.The multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding,leading to amplification of the bactericidal effect.In addition to multivalency-enhanced antibacterial activity,mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic structure.The resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin wounds.The multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.

关键词： healing enable dynamic

Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation

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Bioactive Materials 2022年第3期7卷 1-14页

作者： Jie Sun Yingkang Huang Huan Zhao Junjie Niu Xuwei Ling Can Zhu Lin Wang Huilin Yang Zhilu Yang guoqing pan Qin Shi Department of Orthopaedics The First Affiliated Hospital of Soochow UniversityOrthopaedic Institute of Soochow University899 PinghaiSuzhouJiangsu215031China Affiliated Dongguan Hospital Southern Medical UniversityNo.3 Wandao RoadDongguanGuangdong523059China Guangdong Provincial Key Laboratory of Shock and Microcirculation No.1023 Shatai RoadGuangzhouGuangdong510080China Institute for Advanced Materials School of Materials Science and EngineeringJiangsu University301 Xuefu RoadZhenjiangJiangsu212013China

Upon the osteoporotic condition,sluggish osteogenesis,excessive bone resorption,and chronic inflammation make the osseointegration of bioinert titanium(Ti)implants with surrounding bone tissues difficult,often lead to prosthesis loosening,bone collapse,and implant failure.In this study,we firstly designed clickable mussel-inspired peptides(DOPA-N3)and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions.Then,two dibenzylcyclooctyne(DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain(BMP-2)were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction.We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1.In vitro,the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells(MSCs),and conspicuous immunopolarization-regulation to shift macrophages to alternative(M2)phenotypes and inhibit inflammation,as well as enhancement of osseointegration and mechanical stability in osteoporotic rats.In summary,our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants,which was conducive to the long-term success of Ti implants,especially in the osteoporotic or inflammatory conditions.

关键词： Titanium implant Clickable mussel-inspired peptide Bio-orthogonal reaction Osseointegration Immunopolarization

Dynamic Colloidal Photonic Crystal Hydrogels with Self-Recovery and Injectability

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Research 2021年第1期2021卷 575-585页

作者： Yue Ma Peiyan He Wanli Xie Qiang Zhang Weiling Yin Jianming pan Miao Wang Xin Zhao guoqing pan Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiangJiangsu 212013China School of Chemistry and Chemical Engineering Jiangsu UniversityZhenjiangJiangsu 212013China Jiangsu Agrochem Laboratory ChangzhouJiangsu 213022China Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomHong KongChina

Simulation of self-recovery and diversity of natural photonic crystal(PC)structures remain great challenges for artificial PC materials.Motivated by the dynamic characteristics of PC nanostructures,here,we present a new strategy for the design of hydrogel-based artificial PC materials with reversible interactions in the periodic nanostructures.The dynamic PC hydrogels,derived from self-assembled microgel colloidal crystals,were tactfully constructed by reversible crosslinking of adjacent microgels in the ordered structure via phenylboronate covalent chemistry.As proof of concept,three types of dynamic colloidal PC hydrogels with different structural colors were prepared.All the hydrogels showed perfect self-healing ability against physical damage.Moreover,dynamic crosslinking within the microgel crystals enabled shear-thinning injection of the PC hydrogels through a syringe(indicating injectability or printability),followed by rapid recovery of the structural colors.In short,in addition to the great significance in biomimicry of self-healing function of natural PC materials,our work provides a facile strategy for the construction of diversified artificial PC materials for different applications such as chem-/biosensing,counterfeit prevention,optical display,and energy conversion.

关键词： materials reversible crosslinking

Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration

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Research 2023年第2期2022卷 305-318页

作者： Jiaxiang Bai Gaoran Ge Qing Wang Wenming Li Kai Zheng Yaozeng Xu Huilin Yang guoqing pan Dechun Geng Department of Orthopaedics The First Affiliated Hospital of Soochow University188 Shizi StreetSuzhouJiangsu 215006China Institute for Advanced Materials Schoolof Materials Science and EngineeringJiangsu University301 Xuefu RoadZhenjiang Jiangsu 212013China

For patients with osteoporosis,the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation,migration,and osteogenic differentiation abilities of bone marrow mesenchymal stem cell... 详细信息

关键词： impaired osteoporosis Mimics

Alternative Copper-Based Single-Atom Nanozyme with Superior Multienzyme Activities and NIR-II Responsiveness to Fight against Deep Tissue Infections

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Research 2023年第3期6卷 409-421页

作者： Jiaxiang Bai Yonghai Feng Wenming Li Zerui Cheng Jessica MRosenholm Huilin Yang guoqing pan Hongbo Zhang Dechun Geng Department of Orthopedic Surgery Orthopedic InstituteThe First Affiliated HospitalMedical CollegeSoochow UniversitySuzhouJiangsu 215006P.R.China Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiangJiangsu 212013P.R.China Pharmaceutical Sciences Laboratory Faculty of Science and EngineeringÅbo Akademi UniversityTurku 20520Finland Turku Bioscience Centre University of Turku andÅbo Akademi UniversityTurku 20520Finland

Nanozymes are considered to represent a new era of antibacterial agents,while their antibacterial efficiency is limited by the increasing tissue depth of infection.To address this issue,here,we report a copper and silk fibroin(Cu-SF)complex strategy to synthesize alternative copper single-atom nanozymes(SAzymes)with atomically dispersed copper sites anchored on ultrathin 2D porous N-doped carbon nanosheets(CuN_(x)-CNS)and tunable N coordination numbers in the CuN_(x) sites(x=2 or 4).The CuN_(x)-CNS SAzymes inherently possess triple peroxidase(POD)-,catalase(CAT)-,and oxidase(OXD)-like activities,facilitating the conversion of H_(2)O_(2)and O_(2)into reactive oxygen species(ROS)through parallel POD-and OXD-like or cascaded CAT-and OXD-like reactions.Compared to CuN_(2)-CNS,tailoring the N coordination number from 2 to 4 endows the SAzyme(CuN_(4)-CNS)with higher multienzyme activities due to its superior electron structure and lower energy barrier.Meanwhile,CuN_(x)-CNS display strong absorption in the second near-infrared(NIR-II)biowindow with deeper tissue penetration,offering NIR-II-responsive enhanced ROS generation and photothermal treatment in deep tissues.The in vitro and in vivo results demonstrate that the optimal CuN_(4)-CNS can effectively inhibit multidrug-resistant bacteria and eliminate stubborn biofilms,thus exhibiting high therapeutic efficacy in both superficial skin wound and deep implant-related biofilm infections.

关键词： copper offering eliminate

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 tolerance.However,its biological inertness,poor osteoinduction,and weak antibacterial activity make the clinical applications in a dilemma.Inspired 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 terminal.The peptide enables mussel-like adhesion on PEEK biomaterial surfaces,leaving azido groups for the further steps of biofunctionalizations.In 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 repair.Since 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 regeneration.In 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

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地铁车站内衬墙施工工艺改进技术研究

施工技术（中英文） 2024年第7期53卷 92-95,103页

作者：潘国庆腾达建设集团股份有限公司上海200120

地铁基坑叠合墙中内衬墙施工质量极为重要,通过相关调研发现,内衬墙的传统工艺做法经常会导致墙面出现蜂窝、麻面、开裂、渗漏等质量问题,严重影响车站结构的安全性及使用寿命。提出的止水钢板上部贴膜保护工艺可有效防治止水钢板上半... 详细信息

地铁基坑叠合墙中内衬墙施工质量极为重要,通过相关调研发现,内衬墙的传统工艺做法经常会导致墙面出现蜂窝、麻面、开裂、渗漏等质量问题,严重影响车站结构的安全性及使用寿命。提出的止水钢板上部贴膜保护工艺可有效防治止水钢板上半部易污染的问题,确保了防水节点的止水效果。无缝式下腋角翻口做法延长了渗水路径,提升了施工缝质量,同时下腋角部位减少了一条施工缝,外观质量更佳。全自动智能控制附着式振捣系统实现了全过程机械化振捣操作,提高了混凝土的均匀性和密实度。节水保湿养护膜加强了混凝土养护过程控制。通过施工现场开展的相关试验,针对性研究改进工艺的可操作性与实际应用性,整体提升内衬墙施工质量。

关键词：地铁车站基坑叠合墙内衬墙施工技术

Thermo-responsive imprinted hydrogel with switchable sialic acid recognition for selective cancer cell isolation from blood

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Bioactive Materials 2021年第5期6卷 1308-1317页

作者： Yue Ma Yimei Yin Li Ni Haohan Miao Yingjia Wang Cheng pan Xiaohua Tian Jianming pan Tianyan You Bin Li guoqing pan Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiangJiangsu 212013PR China School of Chemistry and Chemical Engineering Jiangsu UniversityZhenjiangJiangsu 212013PR China Jiangsu Agrochem Laboratory ChangzhouJiangsu 213022PR China Key Laboratory of Modern Agricultural Equipment and Technology Ministry of EducationSchool of Agricultural Equipment EngineeringJiangsu UniversityZhenjiangJiangsu 212013PR China Department of Orthopaedic Surgery The First Affiliated HospitalOrthopaedic InstituteMedical CollegeSoochow UniversitySuzhouJiangsu 215006PR China

In this work,a sialic acid(SA)-imprinted thermo-responsive hydrogel layer was prepared for selective capture and release of cancer cells.The SA-imprinting process was performed at 37℃ using thermo-responsive functional monomer,thus generating switchable SA-recognition sites with potent SA binding at 37℃and weak binding at a lower temperature(e.g.,25℃).Since SA is often overexpressed at the glycan terminals of cell membrane proteins or lipids,the SA-imprinted hydrogel layer could be used for selective cancer cell recognition.Our results confirmed that the hydrogel layer could efficiently capture cancer cells from not only the culture medium but also the real blood samples.In addition,the captured cells could be non-invasively released by lowing the temperature.Considering the non-invasive processing mode,considerable capture efficiency,good cell selectivity,as well as the more stable and durable SA-imprinted sites compared to natural antibodies or receptors,this thermo-responsive hydrogel layer could be used as a promising and general platform for cell-based cancer diagnosis.

关键词： Molecular imprinting Cell capture and release Thermo-responsive hydrogels Molecular recognition Sialic acid