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Guided bone regeneration in long-bone defect with a bilayer mineralized collagen membrane

Collagen and Leather 2024年第1期5卷 85-100页

作者： Fuli Peng Xuelei zhang Yilei Wang Rui Zhao Zhiwei Cao Siyu Chen Yunxuan Ruan Jingjing Wu Tianxi Song Zhiye Qiu Xiao Yang Yi Zeng Xiangdong Zhu Jian Pan xingdong zhang Department of Orthopedics West China HospitalOrthopedic Research InstituteSichuan UniversityChengdu 610041SichuanChina National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064SichuanChina Chengdu Integrated TCM and Western Medicine Hospital Chengdu First People's HospitalChengdu 610041SichuanChina Department of Inspection School of MedicineJiangsu UniversityZhenjiang 212013China State Key Laboratory of Oral Diseases and National Center for Stomatology and National Clinical Research Center for Oral Diseases Department of Oral and Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengdu 610041SichuanChina State Key Laboratory of New Ceramics and Fine Processing Key Laboratory of Advanced Materials of Min-istry of EducationSchool of Materials Science and EngineeringTsinghua UniversityBeijing 100084China

Bone regeneration for large,critical-sized bone defects remains a clinical challenge *** bone regeneration(GBR)is a promising technique for the repair of multiple bone defects,which is widely used in oral and maxillofacial bone defects but is still unsatisfied in the treatment of long bone ***,we successfully fabricated a bilayer mineralized collagen/collagen(MC/Col)-GBR membrane with excellent osteoinductive and barrier function by coating the MC particles prepared via in situ biomimetic mineralization process on one side of a sheet-like pure collagen *** aim of the present study was to investigate the physicochemical properties and biological functions of the MC/Col film,and to further evaluate its bone regeneration efficiency in large bone defect *** infrared spectra and X-ray diffraction patterns confirmed the presence of both hydroxyapatite and collagen phase in the MC/Col film,as well as the chemical interaction between *** microscope,scanning electron microscopy and atomic force microscope showed the uniform distribution of MC particles in the MC/Col film,resulting in a rougher surface compared to the pure Col *** quantitative analysis of surface contact angle,light transmittance and tensile strength demonstrated that the MC/Col film have better hydrophilicity,mechanical properties,light-barrier properties,*** vitro macrophage co-culture experiments showed that the MC/Col film can effectively inhibit macrophage proliferation and fusion,reducing fibrous capsule *** vivo bone repair assessment of a rabbit critical segmental radial defect proved that the MC/Col film performed better than other groups in promoting bone repair and regeneration due to their unique dual osteoinductive/barrier *** findings provided evidence that MC/Col film has a great clinical potential for effective bone defect repair.

关键词： Mineralized collagen Collagen Guided bone regeneration Artificial periosteum Bone defect repair

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Injectable immunoregulatory hydrogels sequentially drive phenotypic polarization of macrophages for infected wound healing

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Bioactive Materials 2024年第11期41卷 193-206页

作者： Yuxiang Wang Chen Zhou Zhulian Li Gong Li Yaping Zou Xing Li Peiyang Gu Jingyi Liu Lang Bai Hong Yan Jie Liang xingdong zhang Yujiang Fan Yong Sun National Engineering Research Center for Biomaterials Sichuan University29#Wangjiang RoadChengduSichuan610064China College of Biomedical Engineering Sichuan University29#Wangjiang RoadChengduSichuan610064China Center of Infectious Diseases West China Hospital of Sichuan University37#Guoxue LaneChengduSichuan610041China Department of Plastic AestheticReparative and Reconstructive Surgery/Wound Repair CenterWest China Second University Hospital of Sichuan University20#Section 3South Renmin RoadChengduSichuan610041China Sichuan Testing Center for Biomaterials and Medical Devices Sichuan University29#Wangjiang RoadChengdu 610064China

Regulating macrophage phenotypes to reconcile the conflict between bacterial suppression and tissue regeneration is ideal for treating infectious skin wounds. Here, an injectable immunoregulatory hydrogel (SrmE20) that sequentially drives macrophage phenotypic polarization (M0 to M1, then to M2) was constructed by integrating anti-inflammatory components and proinflammatory solvents. In vitro experiments demonstrated that the proinflammatory solvent ethanol stabilized the hydrogel structure, maintained the phenolic hydroxyl group activity, and achieved macrophages' proinflammatory transition (M0 to M1) to enhance antibacterial effects. With ethanol depletion, the hydrogel's cations and phenolic hydroxyl groups synergistically regulated macrophages' anti-inflammatory transition (M1 to M2) to initiate regeneration. In the anti-contraction full-thickness wound model with infection, this hydrogel effectively eliminated bacteria and even achieved anti-inflammatory M2 macrophage accumulation at three days post-surgery, accelerated angiogenesis and collagen deposition. By sequentially driving macrophage phenotypic polarization, this injectable immunoregulatory hydrogel will bring new guidance for the care and treatment of infected wounds.

关键词： Sequential immunoregulation Macrophage phenotypic polarization Injectable hydrogel Infected wounds

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Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to inhibit glioma growth

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Regenerative Biomaterials 2024年第5期3卷 121-134页

作者： Yifu Wang Hongfeng Wu Zhu Chen Jun Cao Xiangdong Zhu xingdong zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064P.R.China College of Biomedical Engineering Sichuan UniversityChengdu 610064P.R.China Medical School Kunming University of Science and TechnologyKunming 650500P.R.China Institute of tissue engineering and stem cells Nanchong Central HospitalNorth Sichuan Medical CollegeNanchong 637000P.R.China

Despite a growing body of studies demonstrating the specific antitumor effect of nano-hydroxyapatite(n-HA),the underlying mechanism remained *** reticulum(ER)and mitochondria are two key players in intracellular Ca^(2+)homeostasis and both require Ca^(2+)to ***,the ER–mitochondria interplay coordinates the maintenance of cellular Ca^(2+)homeostasis to prevent any negative consequences from excess of Ca^(2+),hence there needs in-depth study of n-HA effect on *** this study,we fabricated needle-like n-HA to investigate the anti-tumor effectiveness as well as the underlying mechanisms from cellular and molecular *** from in vitro experiments indicated that the growth and invasion of glioma cells were obviously reduced with the aid of *** is interesting to note that the expression of ER stress biomarkers(GRP78,p-IRE1,p-PERK,PERK,and ATF6)were all upregulated after n-HA treatment,along with the activation of the pro-apoptotic transcription factor CHOP,showing that ER stress produced by n-HA triggered cell ***,the increased expression level of intracellular reactive oxygen species and the mitochondrial membrane depolarization,as well as the downstream cell apoptotic signaling activation,further demonstrated the pro-apoptotic roles of n-HA induced Ca^(2+)overload through inducing mitochondria *** in vivo data provided additional evidence that n-HA caused ER stress and mitochondria damage in cells and effectively restrain the growth of glioma ***,the work showed that n-HA co-activated intracellular ER stress and mitochondria damage are critical triggers for cancer cells apoptosis,offering fresh perspectives on ER-mitochondria targeted anti-tumor therapy.

关键词： nano-hydroxyapatite endoplasmic reticulum stress glioma apoptosis protein mitochondria damage

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Advanced application of collagen-based biomaterials in tissue repair and restoration

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Journal of Leather Science and Engineering 2022年第1期4卷 409-427页

作者： Jiayi Zhu Zhulian Li Yaping Zou Gonggong Lu Alfredo Ronca Ugo D’Amora Jie Liang Yujiang Fan xingdong zhang Yong Sun National Engineering Research Center for Biomaterials Sichuan University29#Wangjiang RoadChengdu 610064People’s Republic of China Institute of Polymers Composites and BiomaterialsNational Research CouncilNaplesItaly College of Biomedical Engineering Sichuan University29#Wangjiang RoadChengdu 610064People’s Republic of China Department of Neurosurgery West China HospitalSichuan University37#Guoxue LaneChengdu 610041SichuanPeople’s Republic of China Sichuan Testing Center for Biomaterials and Medical Devices Sichuan University29 Wangjiang RoadChengdu 610064People’s Republic of China.

In tissue engineering,bioactive materials play an important role,providing structural support,cell regulation and establishing a suitable microenvironment to promote tissue *** the main component of extracellular matrix,collagen is an important natural bioactive material and it has been widely used in scientific research and clinical *** is available from a wide range of animal origin,it can be produced by synthesis or through recombinant protein production *** use of pure collagen has inherent disadvantages in terms of physico-chemical *** this reason,a processed collagen in different ways can better match the specific requirements as biomaterial for tissue ***,collagen may be used in bone/cartilage regeneration,skin regeneration,cardiovascular repair and other fields,by following different processing methods,including cross-linked collagen,complex,structured collagen,mineralized collagen,carrier and other forms,promoting the development of tissue *** review summarizes a wide range of applications of collagen-based biomaterials and their recent progress in several tissue regeneration ***,the application prospect of bioactive materials based on collagen was outlooked,aiming at inspiring more new progress and advancements in tissue engineering research.

关键词： Collagen Bioactive material Tissue engineering Regeneration Repair

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Construction of a magnesium hydroxide/graphene oxide/hydroxyapatite composite coating on Mg-Ca-Zn-Ag alloy to inhibit bacterial infection and promote bone regeneration

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Bioactive Materials 2022年第12期7卷 354-367页

作者： Bo Yuan Hewei Chen Rui Zhao Xuangeng Deng Guo Chen Xiao Yang Zhanwen Xiao Antoniac Aurora Bita Ana Iulia Kai zhang Xiangdong Zhu Antoniac Vasile Iulian Shen Hai xingdong zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu610064China College of Biomedical Engineering Sichuan UniversityChengdu610064China Sichuan Provincial Orthopedic Hospital Chengdu610041China Faculty of Materials Science and Engineering University Politehnica of Bucharest060042BucharestRomania Academy of Romanian Scientists 050094BucharestRomania

The improved corrosion resistance, osteogenic activity, and antibacterial ability are the key factors for promoting the large-scale clinical application of magnesium (Mg)-based implants. In the present study, a novel nanocomposite coating composed of inner magnesium hydroxide, middle graphene oxide, and outer hydroxyapatite (Mg(OH)_(2)/GO/HA) is constructed on the surface of Mg-0.8Ca-5Zn-1.5Ag by a combined strategy of hydrothermal treatment, electrophoretic deposition, and electrochemical deposition. The results of material characterization and electrochemical corrosion test showed that all the three coatings have high bonding strength, hydrophilicity and corrosion resistance. In vitro studies show that Mg(OH)2 indeed improves the antibacterial activity of the substrate. The next GO and GO/HA coating procedures both promote the osteogenic differentiation of MC3T3-E1 cells and show no harm to the antibacterial activity of Mg(OH)2 coating, but the latter exhibits the best promoting effect. In vivo studies demonstrate that the Mg alloy with the composite coating not only ameliorates osteolysis induced by bacterial invasion but also promotes bone regeneration under both normal and infected conditions. The current study provides a promising surface modification strategy for developing multifunctional Mg-based implants with good corrosion resistance, antibacterial ability and osteogenic activity to enlarge their biomedical applications.

关键词： Mg alloy Composite coating Corrosion resistance Antibacterial ability Osteogenic activity

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Strategies of strengthening mechanical properties in the osteoinductive calcium phosphate bioceramics

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Regenerative Biomaterials 2023年第1期10卷 561-573页

作者： Qipeng Li Cong Feng Quanle Cao Wei Wang Zihan Ma Yonghao Wu Tinghan He Yangtian Jing Wenxuan Tan Tongxiao Liao Jie Xing Xiangfeng Li Ye Wang Yumei Xiao Xiangdong Zhu xingdong zhang College of Chemical Engineering Sichuan UniversityChengdu 610065China National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengdu 610065China College of Materials Science and Engineering Sichuan UniversityChengdu 610064China

Calcium phosphate(CaP)bioceramics are widely applied in the bone repairing field attributing to their excellent biological properties,especially ***,their applications in load-bearing or segmental bone defects are severely restricted by the poor mechanical *** is generally considered that it is challenging to improve mechanical and biological properties of CaP bioceramics *** to now,various strategies have been developed to enhance mechanical strengths of CaP ceramics,the achievements in recent researches need to be urgently *** this review,the effective and current means of enhancing mechanical properties of CaP ceramics were comprehensively summarized from the perspectives of fine-grain strengthening,second phase strengthening,and sintering process ***’s more,the further improvement of mechanical properties for CaP ceramics was prospectively proposed including heat treatment and ***,this review put forward the direction about how to compatibly improve mechanical properties of CaP ceramics,which can provide data and ideas for expanding the range of their clinical applications.

关键词： CaP ceramics strategy mechanical property osteoinductivity enhancement

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The biological effect of recombinant humanized collagen on damaged skin induced by UV-photoaging:An in vivo study

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Bioactive Materials 2022年第5期7卷 154-165页

作者： Jing Wang He Qiu Yang Xu Yongli Gao Peijie Tan Rui Zhao Zhanhong Liu Yajun Tang Xiangdong Zhu Chongyun Bao Hang Wang Hai Lin xingdong zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengduSichuan 610064China College of Biomedical Engineering Sichuan UniversityChengduSichuan 610064China West China School/Hospital of Stomatology Sichuan UniversityChengduSichuan 610064China

The application of medical devices to repair skin damage is clinically accepted and natural polymer enjoys an important role in this field,such as collagen or hyaluronic acid,***,the biosafety and efficacy of these implants are still *** this study,a skin damage animal model was prepared by UV-photoaging and recombinant humanized type Ⅲ collagen(rhCol Ⅲ)was applied as a bioactive material to implant in vivo to study its biological effect,comparing with saline and uncrosslinked hyaluronic acid(HA).Animal skin conditions were non-invasively and dynamically monitored during the 8 weeks *** observation,specific gene expression and other molecular biological methods were applied by the end of the animal *** results indicated that rhCol Ⅲ could alleviate the skin photoaging caused by UV radiation,including reduce the thickening of epidermis and dermis,increase the secretion of Collagen Ⅰ(Col Ⅰ)and Collagen Ⅲ(Col Ⅲ)and remodel of extracellular matrix(ECM).Although the cell-material interaction and mechanism need more investigation,the effect of rhCol Ⅲ on damaged skin was discussed from influence on cells,reconstruction of ECM,and stimulus of small biological molecules based on current *** conclusion,our findings provided rigorous biosafety information of rhCol Ⅲ and approved its potential in skin repair and *** enormous efforts still need to be made to achieve successful translation from bench to clinic,the recombinant humanized collagen showed superiorities from both safety and efficacy aspects.

关键词： Recombinant collagen TypeⅢcollagen Skin regeneration Safety and efficacy Biological effect

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Nanofibrous polypeptide hydrogels with collagen-like structure as biomimetic extracellular matrix

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Collagen and Leather 2023年第2期5卷 81-93页

作者： Chengkun Zhao Xing Li Shaoquan Bian Weinan Zeng Alfredo Ronca Ugo D'Amora Maria Grazia Raucci Jie Liang Yong Sun Qing Jiang Yujiang Fan Luigi Ambrosio xingdong zhang National Engineering Research Center for Biomaterials Sichuan University29#Wangjiang RoadChengdu 610064People's Republic of China College of Biomedical Engineering Sichuan University29#Wangjiang RoadChengdu 610064People's Republic of China Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhen 518055People's Republic of China Orthopedic Research Institution Department of OrthopedicsWest China HospitalSichuan UniversityChengdu 610041People's Republic of China Institute of Polymers Composites and BiomaterialsNational Research Council80125 NaplesItaly

Supramolecular peptides exhibit obvious similarities with collagen fibers in terms of self-assembly characteristics,nanofibrous structure,and responsiveness to external ***,a series of supramolecular peptides were developed by altering the amino acid sequence,enabling the self-assembly of three types of 4-biphenylacetic acid(BPAA)-tripeptides into fibrous hydrogel through hydrogen bonding and n-n stacking under the influence of ion *** electron and scanning electron microscopies revealed that the diameter of the fiber within nanofibrous hydrogels was~10 and~40 nm,respectively,which was similar with the self-assembled collagen *** this reason,these hydrogels could be considered as a biomimetic extracellular ***,the gelation concentration induced by ions was even lower than 0.66 wt%,with an elastic modulus of~0.27 kPa,corresponding to a water content of 99.34 wt%.In addition,the three supramolecular hydrogels were found to be good substrates for L929 cell adhesion and MC-3T3 cell *** overall results implied that BPAA-based hydrogels have a lucrative application potential as cell carriers.

关键词： Collagen-like Supramolecular peptides Nanofibrous hydrogel Ion-induction Biomimetic extracellular matrix

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细菌在生物活性钛表面的粘附行为

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稀有金属材料与工程 2009年第7期38卷 1242-1245页

作者：甘露杨帮成张兴栋四川大学四川成都610064

以经酸碱处理、碱热处理和阳极氧化处理后的生物活性钛材为研究对象,对材料进行了表面形貌分析和表面能的测定,并选用常见感染细菌金黄色葡萄球菌和大肠杆菌为研究菌株,采用体外共培养法培养,通过SEM对细菌的形态、在材料表面的粘附情... 详细信息

以经酸碱处理、碱热处理和阳极氧化处理后的生物活性钛材为研究对象,对材料进行了表面形貌分析和表面能的测定,并选用常见感染细菌金黄色葡萄球菌和大肠杆菌为研究菌株,采用体外共培养法培养,通过SEM对细菌的形态、在材料表面的粘附情况和粘附量进行观察,通过MTT法对细菌粘附量进行半定量测定,综合评价生物活性钛的表面结构对细菌增殖和粘附的影响。结果表明,在3种生物活性钛材料表面,细菌的粘附和增殖受材料表面形貌影响显著,其中碱热处理钛表面和阳极氧化钛表面不利于细菌的增殖和粘附,显示出较好的抑菌性能。

关键词：生物活性钛金黄色葡萄球菌大肠杆菌细菌粘附

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Characterization of recombinant humanized collagen type III and its influence on cell behavior and phenotype

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Journal of Leather Science and Engineering 2022年第1期4卷 452-464页

作者： Jing Wang Hong Hu Jian Wang He Qiu Yongli Gao Yang Xu Zhanhong Liu Yajun Tang Lu Song John Ramshaw Hai Lin xingdong zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064SichuanChina College of Biomedical Engineering Sichuan UniversityChengdu 610064SichuanChina Shanxi Jinbo Pharmaceutical Co. Ltd.Taiyuan 030031ShanxiChina West China School/Hospital of Stomatology Sichuan UniversityChengdu 610064SichuanChina Swinburne University of Technology MelbourneAustralia.

Collagen made a tremendous impact in the field of regenerative medicine as a bioactive *** decades,collagen has been used not only as a scaffolding material but also as an active component in regulating cells’biological behavior and ***,animal-derived collagen as a major source suffered from problems of immunogenicity,risk of viral infection,and the unclear relationship between bioactive sequence and *** humanized collagen(rhCol)provided alternatives for regenerative medicine with more controllable ***,the characterization of rhCol and the interaction between rhCol and cells still need further investigation,including cell behavior and *** current study preliminarily demonstrated that recombinant humanized collagen type III(rhCol III)conformed to the theoretical amino acid sequence and had an advanced structure resembling bovine ***,rhCol III could facilitate basal biological behaviors of human skin fibroblasts,such as adhesion,proliferation and *** III was beneficial for some extracellular matrix-expressing cell *** study would shed light on the mechanism research of rhCol and cell interactions and further understanding of effectiveness in tissue regeneration.

关键词： Recombinant collagen Collagen type III Advanced structure Cell behavior Cell phenotype

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