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Fractal Design Boosts Extrusion-Based 3D Printing of Bone-Mimicking Radial-Gradient Scaffolds

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Research 2021年第1期2021卷 1583-1595页

作者： Huawei Qu Zhenyu Han Zhigang Chen Lan Tang Chongjian Gao Kaizheng Liu haobo pan Hongya Fu Changshun Ruan School of Mechatronics Engineering Harbin Institute of TechnologyHarbin 150001China Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China

Although extrusion-based three-dimensional(EB-3D)printing technique has been widely used in the complex fabrication of bone tissue-engineered scaffolds,a natural bone-like radial-gradient scaffold by this processing method is of huge challenge and still *** by a typical fractal structure of Koch snowflake,for the first time,a fractal-like porous scaffold with a controllable hierarchical gradient in the radial direction is presented via fractal design and then implemented by EB-3D *** radial-gradient structure successfully mimics the radially gradual decrease in porosity of natural bone from cancellous bone to cortical ***,we create a design-to-fabrication workflow with embedding the graded data on basis of fractal design into digital processing to instruct the extrusion process of fractal-like ***,by a combination of suitable extruded inks,a series of bone-mimicking scaffolds with a 3-iteration fractal-like structure are fabricated to demonstrate their superiority,including radial porosity,mechanical property,and *** study showcases a robust strategy to overcome the limitations of conventional EB-3D printers for the design and fabrication of functionally graded scaffolds,showing great potential in bone tissue engineering.

关键词： fractal porosity printing

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Small-molecule amines:a big role in the regulation of bone homeostasis

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Bone Research 2023年第3期11卷 457-480页

作者： Qian Zhang Jirong Yang Nan Hu Juan Liu Huan Yu haobo pan Di Chen Changshun Ruan Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China Department of Nephrology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020 GuangdongChina Research Center for Computer-Aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Shenzhen Healthemes Biotechnology Co. Ltd.Shenzhen 518102China Faculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Numerous small-molecule amines(SMAs)play critical roles in maintaining bone homeostasis and promoting bone regeneration regardless of whether they are applied as drugs or *** the one hand,SMAs promote bone formation or inhibit bone resorption through the regulation of key molecular signaling pathways in osteoblasts/osteoclasts;on the other hand,owing to their alkaline properties as well as their antioxidant and anti-inflammatory features,most SMAs create a favorable microenvironment for bone ***,due to a lack of information on their structure/bioactivity and underlying mechanisms of action,certain SMAs cannot be developed into drugs or biomaterials for bone disease *** this review,we thoroughly summarize the current understanding of SMA effects on bone homeostasis,including descriptions of their classifications,biochemical features,recent research advances in bone biology and related regulatory mechanisms in bone *** addition,we discuss the challenges and prospects of SMA translational research.

关键词： amines biomaterials alkaline

Recent progress in functional metal-organic frameworks for bio-medical application

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Regenerative Biomaterials 2024年第2期3卷 37-54页

作者： Wenwen Chai Xiaochen Chen Jing Liu Liyan Zhang Chunyu Liu Li Li John Robert Honiball haobo pan Xu Cui Deping Wang School of Materials Science and Engineering Tongji UniversityShanghai 201804China Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055China Department of Orthopaedics&Traumatology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Metal-organic frameworks(MOFs)have a high specific surface area,adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly,which has intrigued wide interest in a broad range of *** the arena of biomedical engineering,the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release,with promising applications in bio-detection,disease therapy,tissue healing,and other *** review summa-rizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small *** *** hvdrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of *** this basis,research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery,tissue repair,disease treatment,bio-detection and imaging is surveyed,and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated,which may provide some inspiration and reference for further development of MOF for bio-medical applications.

关键词： metal-organic frameworks porous functionalization tissue repair disease treatment

Controlled release and biocompatibility of polymer/titania nanotube array system on titanium implants

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Bioactive Materials 2017年第1期2卷 44-50页

作者： Tingting Wang Zhengyang Weng Xiangmei Liu Kelvin W.K.Yeung haobo pan Shuilin Wu Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional MaterialsHubei Key Laboratory of Polymer MaterialsSchool of Materials Science&EngineeringHubei UniversityWuhanChina Division of Spine Surgery Department of Orthopaedics&TraumatologyLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong KongChina Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055China

Bacterial infection and tissue inflammation are the major causes of early failure of titanium-based orthopedic implants;thus,surgical implants with tunable drug releasing properties represent an appealing way to address some of these problems of bacterial infection and tissue inflammation in early age of orthopedic *** this work,a hybrid surface system composed of biodegradable poly(lactic-coglycolic acid)(PLGA)and titania nanotubes(TNTs)has been successfully constructed on Ti implants with the aim of preventing bacterial infection via long-term drug *** varying the size of the TNTs and the thickness of the polymer film,the drug release profile can be tuned to achieve the optimal therapeutic action throughout the treatment *** size of TNTs plays a dominant role in the drug loading dose of TNTs/PLGA hybrid *** this work,TNTs with an average size of 80 nm can achieve the largest loading *** on the polymer thickness,significant improvement in the drug release characteristics is attained,for instance,reduced burst release(from 84%to 27%)and overall release time extended from 5 to over 40 *** addition,the PLGA layers may favor the proliferation and osteogenesis of MC3T3-E1 mouse cells at an earlier ***,this TNT/PLGA hybrid surface system can be employed as an effective bioplatform for improving both self-antibacterial performance and biocompatibility of Ti-based biomaterials.

关键词： Antibacterial Biocompatibility Coating Drug delivery Implants

Dual stimulus responsive borosilicate glass(BSG)scaffolds promote diabetic alveolar bone defectsrepair by modulating macrophage phenotype

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Bioactive Materials 2023年第8期26卷 231-248页

作者： Pengfei Tian Limin Zhao Jua Kim Xian Li Chunyu Liu Xu Cui Tao Liang Yunbo Du Xiehui Chen haobo pan Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen518055PR China Shenzhen Longhua District Central Hospital Shenzhen518000PR China Shenzhen Healthemes Biotechnology Co.Ltd Shenzhen518102PR China

The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory *** a result,the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function,which is mostly disturbed by constant *** this study,we developed glucose and hydrogen peroxide dual-responsive borosilicate glass(BSG)scaffolds loaded with epigallocatechin gallate(EGCG)to synergistically modulate the abnormal inflammation of diabetic alveolar bone *** was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic ***,EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory ***,the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely *** altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone,showing promise for the treatment of alveolar defect in diabetic patients.

关键词： Borosilicate Epigallocatechin gallate(EGCG) Alveolar bone Autophagy Mitochondria Macrophage immunomodulatory Diabetes

Corrosion mechanism of micro-arc oxidation treated biocompatible AZ31 magnesium alloy in simulated body fluid

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Progress in Natural Science:Materials International 2014年第5期24卷 516-522页

作者： Ying Li Fang Lu Honglong Li Wenjun Zhu haobo pan Guoxin Tan Yonghua Lao Chengyun Ning Guoxin Ni School of Materials Science and Engineering South China University of Technology School of Chinese Materia Medica Guangzhou University of Chinese Medicine Department of Prosthodontics Guanghua School of Stomatology Sun Yat-sen University Center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced Technology Chinese Academy of Science Institute of Chemical Engineering and Light Industry Guangdong University of Technology Guangdong Province Key Laboratory of Biomedical Engineering South China University of Technology Department of Orthopeadics and Traumatology Nanfang Hospital Southern Medical University

The rapid degradation of magnesium(Mg) based alloys has prevented their further use in orthopedic trauma fixation and vascular intervention,and therefore it is essential to investigate the corrosion mechanism for improving the corrosion resistance of these alloys. In this work, the effect of applied voltage on the surface morphology and the corrosion behavior of micro-arc oxidation(MAO) with different voltages were carried out to obtain biocompatible ceramic coatings on AZ31 Mg alloy. The effects of applied voltage on the surface morphology and the corrosion behavior of MAO samples in the simulated body fluid(SBF) were studied systematically. Scanning electron microscope(SEM) and X-ray diffractometer(XRD)were employed to characterize the morphologies and phase compositions of coating before and after corrosion. The results showed that corrosion resistance of the MAO coating obtained at 250 V was better than the others in SBF. The dense layer of MAO coating and the corrosion precipitation were the key factors for corrosion behavior. The corrosion of precipitation Mg(OH)2and the calcium phosphate(Ca–P) minerals on the surface of MAO coatings could enhance their corrosion resistance effectively. In addition, the mechanism of MAO coated Mg alloys was proposed.

关键词： Biodegradable Mechanism Micro-arc oxidation AZ31 magnesium alloy Corrosion resistance

In vitro and in vivo antibacterial performance of Zr&O PIII magnesium alloys with high concentration of oxygen vacancies

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Bioactive Materials 2021年第10期6卷 3049-3061页

作者： Tao Liang Lilan Zeng Yunzhu Shi haobo pan Paul K.Chu Kelvin W.K.Yeung Ying Zhao Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhen518055China University of Chinese Academy of Sciences Beijing100049China Department of Physics Department of Materials Science and EngineeringDepartment of Biomedical EngineeringCity University of Hong KongTat Chee AvenueKowloonHong KongChina Department of Orthopaedics and Traumatology The University of Hong KongHong KongChina

The effects of dual Zr and O plasma immersion ion implantation(Zr&O PIII)on antibacterial properties of ZK60 Mg alloys are systematically *** results show that a hydrophobic,smooth,and ZrO_(2)-containing graded film is *** assessment shows that the corrosion rate of the plasma-treated Mg alloy decreases and the decreased degradation rate is attributed to the protection rendered by the surface *** vitro and in vivo antibacterial tests reveal Zr&O PIII ZK60 presents higher antibacterial rate compared to Zr PIII ZK60 and untreated *** hydrophobic and smooth surface suppresses bacterial *** concentration of oxygen vacancies in the surface films are determined by X-ray photoelectron spectroscopy(XPS),UV-vis diffuse reflectance spectra(UV-vis DRS)and electron paramagnetic resonance(EPR)and involved in the production of reactive oxygen species(ROS).The higher level of ROS expression inhibits biofilm formation by down-regulating the expression of icaADBC genes but up-regulating the expression of icaR *** addition,Zr&O PIII improves cell viability and initial cell adhesion confirming good *** Zr&O PIII is a simple and practical means to expedite clinical acceptance of biodegradable magnesium alloys.

关键词： Magnesium alloy Plasma immersion ion implantation Degradation ZrO_(2) Antibacterial property

Akermanite used as an alkaline biodegradable implants for the treatment of osteoporotic bone defect

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Bioactive Materials 2016年第2期1卷 151-159页

作者： Wenlong Liu Ting Wang Xiaoli Zhao Xiuli Dan William W.Lu haobo pan Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of OrthopaedicsThe University of Hong Kong-Shenzhen HospitalUniversity of Hong KongShenzhenChina School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong Kong Department of Orthopaedics and Traumatology Faculty of MedicineThe University of Hong KongHong Kong

In osteoporosis scenario, tissue response to implants is greatly impaired by the deteriorated boneregeneration microenvironment. In the present study, a Mg-containing akermanite (Ak) ceramic wasemployed for the treatment of osteoporotic bone defect, based on the hypothesis that both beneficialions (e.g. Mg^2+ ect.) released by the implants and the weak alkaline microenvironment pH (μe-pH) itcreated may play distinct roles in recovering the abnormal bone regeneration by stimulating osteoblasticanabolic effects. The performance of Ak, b-tricalcium phosphate (β-TCP) and Hardystone (Har) in healinga 3 mm bone defect on the ovariectomized (OVX) osteoporotic rat model was evaluated. Our resultsindicated that, there's more new bone formed in Ak group than in β-TCP or Har group at week 9. Theinitial me-pHs of Ak were significantly higher than that of the β-TCP and Blank group, and this weakalkaline condition was maintained till at least 9 weeks post-surgery. Increased osteoblastic activity whichwas indicated by higher osteoid secretion was observed in Ak group at week 4 to week 9. An intermediatelayer which was rich in phosphorus minerals and bound directly to the new forming bone wasdeveloped on the surface of Ak. In a summary, our study demonstrates that Ak exhibits a superior boneregenerative performance under osteoporosis condition, and might be a promising candidate for thetreatment of osteoporotic bone defect and fracture.

关键词： Osteoporotic bone defect Akermanite Material-bone interface Microenvironment pH

Osteogenic and anti-tumor Cu and Mn-doped borosilicate nanoparticles for syncretic bone repair and chemodynamic therapy in bone tumor treatment

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Bioactive Materials 2022年第6期7卷 1-15页

作者： Libin pang Renliang Zhao Jing Chen Jingxin Ding Xiaochen Chen Wenwen Chai Xu Cui Xiaolin Li Deping Wang haobo pan School of Materials Science and Engineering Tongji UniversityShanghai201804China Department of Orthopedic Surgery and Shanghai Institute of Microsurgery on ExtremitiesShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhen518055China Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai201203China

Critical bone defects caused by extensive excision of malignant bone tumor and the probability of tumor recurrence due to residual tumor cells make malignant bone tumor treatment a major clinical *** present therapeutic strategy concentrates on implanting bone substitutes for defect filling but suffers from failures in both enhancing bone regeneration and inhibiting the growth of tumor ***,Cu and Mn-doped borosilicate nanoparticles(BSNs)were developed for syncretic bone repairing and anti-tumor treatment,which can enhance bone regeneration through the osteogenic effects of Cu^(2+) and Mn^(3+) ions and meanwhile induce tumor cells apoptosis through the hydroxyl radicals produced by the Fenton-like reactions of Cu^(2+) and Mn^(3+) *** vitro study showed that both osteogenic differentiation of BMSCs and angiogenesis of endothelial cells were promoted by BSNs,and consistently the critical bone defects of rats were efficiently repaired by BSNs through in vivo ***,BSNs could generate hydroxyl radicals through Fenton-like reactions in the simulated tumor microenvironment,promote the generation of intracellular reactive oxygen species,and eventually induce tumor cell ***,subcutaneous tumors of mice were effectively inhibited by BSNs without causing toxic side effects to normal tissues and ***,Cu and Mn-doped BSNs developed in this work performed dual functions of enhancing osteogenesis and angiogenesis for bone regeneration,and inhibiting tumor growth for chemodynamic therapy,thus holding a great potential for syncretic bone repairing and anti-tumor therapy.

关键词： Borosilicate Bio-ceramics Bone regeneration Tumor therapy Chemodynamic therapy Bone tumor treatment