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Anti-inflammatory and anabolic biphasic scaffold facilitates osteochondral tissue regeneration in osteoarthritic joints

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Journal of Materials science & Technology 2023年第25期156卷 20-31页

作者： Xiangbo Meng Ling Li Cuishan Huang Keda Shi Qingqiang Zeng Chunyi Wen Sibylle Grad Mauro Alini Ling Qin Xinluan Wang Translational Medicine R&D Center Institute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China AO Research Institute Davos Clavadelerstrasse 8Davos Platz 7270Switzerland Musculoskeletal Research laboratory Department of Orthopaedics & TraumatologyThe Chinese University of Hong KongHong Kong SAR 999077China CAS-HK joint Lab of biomaterials Joint Laboratory of Chinese Academic of Science and Hong Kong for BiomaterialsTranslational Medicine Research and Development CenterShenzhen Institutes of Advanced Technology of Chinese Academy of Sciences and The Chinese University of Hong KongChina Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong SAR 999077China

Osteochondral defects (OCD) are common but difficult to heal due to the low intrinsic repair capacity of cartilage and its complex hierarchical structure. In osteoarthritis (OA), OCD become more challenging to repair as both cartilage and subchondral bone regeneration are further impaired due to the arthritic environment. Numerous biomaterials have been developed and tested in osteochondral defects while ignoring the inflammatory environment. To target this challenging underlying pathophysiology, we designed and fabricated a biphasic porous and degradable scaffold incorporating anti-inflammatory and anabolic molecules by low-temperature rapid prototyping technology, and its effects on promoting osteochondral regeneration were evaluated using our well-established OA-OCD rabbit model. The biphasic porous scaffolds consisted of poly lactic-co-glycolic acid (PLGA) with kartogenin (KGN) for cartilage repair and PLGA and β-calcium phosphate (PLGA/β-TCP) with cinnamaldehyde (CIN) for subchondral bone repair. KGN is a molecule for promoting chondrogenesis and CIN is a phytomolecule for enhancing osteogenesis and alleviating inflammation. The biphasic scaffolds PLGA/KGN-PLGA/β-TCP/CIN (PK/PTC) with bio-mimic structure provided stable mechanical properties and exhibited excellent biocompatibility to support cell adhesion, proliferation, migration, and distribution. Furthermore, KGN and CIN within biphasic scaffolds could be released in a controlled and sustained mode, and the biphasic scaffold degraded slowly in vitro . Evaluating the repair of 16-weeks post-implantation into critically sized OA-OCD rabbit models revealed that the biphasic scaffold could promote subchondral bone and cartilage regeneration, as well as reverse subchondral osteosclerosis caused by inflammation in vivo . These findings support the utilization of the PK/PTC scaffold for osteochondral regeneration and provide a promising potential strategy for clinical application for the treatment of patients with

关键词： Biphasic scaffold Osteochondral defect Osteoarthritis Kartogenin Cinnamaldehyde Anti-inflammation

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Nanoparticle–Cartilage Interaction: Pathology-Based Intra-articular Drug Delivery for Osteoarthritis Therapy

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Nano-Micro Letters 2021年第10期13卷 29-76页

作者： Xu Li Bingyang Dai Jiaxin Guo Lizhen Zheng Quanyi Guo Jiang Peng Jiankun Xu Ling Qin Musculoskeletal Research laboratory Department of Orthopedics and TraumatologyThe Chinese University of Hong KongSha TinHong KongSARPeople’s Republic of China joint laboratory of chinese academic of science and hong kong for biomaterials The Chinese University of Hong KongSha TinHong KongSARPeople’s Republic of China Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLAInstitute of OrthopedicsChinese PLA General HospitalBeijingPeople’s Republic of China Innovative Orthopedic Biomaterial and Drug Translational Research laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongSha TinHong KongSARPeople’s Republic of China

Osteoarthritis is the most prevalent chronic and debilitating joint disease,resulting in huge medical and socioeconomic ***-articular administration of agents is clinically used for pain ***,the effectiveness is inapparent caused by the rapid clearance of *** overcome this issue,nanoparticles as delivery systems hold considerable promise for local control of the pharmacokinetics of therapeutic *** the therapeutic programs are inseparable from pathological progress of osteoarthritis,an ideal delivery system should allow the release of therapeutic agents upon specific features of *** this review,we firstly introduce the pathological features of osteoarthritis and the design concept for accurate localization within cartilage for sustained drug ***,we review the interactions of nanoparticles with cartilage microenvironment and the rational ***,we highlight advances in the therapeutic schemes according to the pathology ***,armed with an updated understanding of the pathological mechanisms,we place an emphasis on the development of“smart”bioresponsive and multiple modality nanoparticles on the near horizon to interact with the pathological *** anticipate that the exploration of nanoparticles by balancing the efficacy,safety,and complexity will lay down a solid foundation tangible for clinical translation.

关键词： Nanoparticle Drug delivery Osteoarthritis Articular cartilage Nanomedicine

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Affinity-guided protein conjugation: the trilogy of covalent protein labeling, assembly and inhibition

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science China Chemistry 2016年第7期59卷 853-861页

作者： Yongsheng Yu Jiang Xia Center of Novel biomaterials Department of Chemistry Chinese University of Hong Kong

Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an "affinity-guided covalent conjugation" strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua none of this reaction. Specific noncovalent interaction of a ligand derivative(which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made "reactive peptides" for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of "affinity-guided covalent conjugation" in various applications.

关键词： peptide-peptide interaction covalent labeling bioconjugation reaction protein assembly inhibitor signal transduction affinity-guided reaction

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Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice

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Bioactive Materials 2021年第5期6卷 1341-1352页

作者： Hao Yao Jiankun Xu Jiali Wang Yifeng Zhang Nianye Zheng Jiang Yue Jie Mi Lizhen Zheng Bingyang Dai Wenhan Huang Shuhang Yung Peijie Hu Yechun Ruan Qingyun Xue Kiwai Ho Ling Qin Musculoskeletal Research laboratory Department of Orthopaedics&TraumatologyFaculty of MedicineThe Chinese University of Hong KongHong KongChina Innovative Orthopaedic Biomaterial and Drug Translational Research laboratory Li Ka Shing Institute of HealthThe Chinese University of Hong KongHong KongChina joint laboratory of chinese academic of science and hong kong for biomaterials The Chinese University of Hong KongHong KongChina School of Biomedical Engineering Sun Yat-sen UniversityGuangzhouPR China School of Life science and Technology Shanghai Tech UniversityShanghaiPR China Department of Biomedical Engineering Polytechnic University of Hong KongHong KongChina Department of Orthopedics Beijing HospitalNo.5th Clinical Medical CollageHealth Science CenterPeking UniversityBeijingPR China

Introduction:We previously demonstrated that magnesium ions(Mg^(2+))was a novel therapeutic alternative for osteoarthritis(OA)through promoting the hypoxia inducible factor-1α(HIF-1α)-mediated cartilage matrix ***,oxidative stress can inhibit the expression of HIF-1α,amplify the inflammation that potentially impairs the therapeutic efficacy of Mg^(2+) in ***(VC),a potent antioxidant,may enhance the efficacy of Mg^(2+) in OA *** study aims to investigate the efficacy of combination of Mg^(2+)and VC on alleviating joint destruction and pain in *** and methods:Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline,MgCl2(0.5 mol/L),VC(3 mg/ml)or MgCl2(0.5 mol/L)plus VC(3 mg/ml)at week 2 post-operation,twice weekly,for 2 *** pain and pathological changes were assessed by gait analysis,histology,western blotting and ***:Mg^(2+) and VC showed additive effects to significantly alleviate the joint destruction and *** efficacy of this combined therapy could sustain for 3 months after the last *** demonstrated that VC enhanced the promotive effect of Mg^(2+) on HIF-1αexpression in ***,combination of Mg^(2+) and VC markedly promoted the M2 polarization of macrophages in ***,combination of Mg^(2+) and VC inhibited osteophyte formation and expressions of pain-related ***:Intra-articular administration of Mg^(2+)and VC additively alleviates joint destruction and pain in *** current formulation may be a cost-effective alternative treatment for OA.

关键词： Osteoarthritis Magnesium Vitamin C Cartilage Inflammation Osteophyte

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Dielectric Investigations on How Mg Salt Is Dispersed in and Released from Polylactic Acid

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chinese Journal of Polymer science 2014年第4期32卷 497-508页

作者： Yu-jie Cao 朱丹 To Ngai Ling Qin Chi Wu Jian Shen Jiangsu Key laboratory of Bio-functional Materials College of Chemistry and Materials ScienceNanjing Normal University Department of Chemistry The Chinese University of Hong Kong The Musculoskeletal Research laboratory Department of Orthopaedics and TraumatologyThe Chinese University of Hong Kong

Composite biomaterials made of biodegradable polylactic acid （PLA） and bioactive magnesium （Mg） salt are developed for orthopaedic implants or metal implant coatings. The releasing of Mg salt into the biological environment benefits the bone growth, while with the releasing of Mg salt and degradation of PLA there forms a porous scaffold for tissue engineering. The size and morphology of the salt and voids are adjustable with such preparation conditions as salt content, pH of casting solution, and the solidification rate, so that we can control the salt releasing and degradation rate of PLA. Dielectric spectroscopy is used to investigate the dispersive structures of Mg salt and voids in the polymer matrix and to monitor the in situ releasing of Mg salts in the simulated body fluid （SBF）. The current study provides us with an orthopedic biomaterial with controllable multi-phase structures, and a tool to investigate the in vivo behaviors of biomaterials.

关键词： Dielectric spectroscopy Inorganic-polymer composite Orthopaedic biomaterials Biodegradation Bioactivity.

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Aggregation-induced emission (AIE) luminescent materials boosting optical storage into the new era of petabit-level capacity

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Aggregate 2024年第3期5卷 1-3页

作者： Siwei Zhang Pengfei Zhang Ben Zhong Tang Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and ReconstructionThe Hong Kong University of Science and TechnologyHong KongChina Guangdong Key laboratory of Nanomedicine CAS-HK Joint Lab of BiomaterialsCAS Key Laboratory of Biomedical Imaging Science and SystemShenzhen Engineering Laboratory of Nanomedicine and NanoformulationsCAS Key Lab for Health InformaticsShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdongChina School of science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhen(CUHK-Shenzhen)ShenzhenGuangdongChina

The recording of information stands as the most significant milestone in human ***,the recording and storage of information have undergone a technological evolution from paintings to carvings,scribing,and *** invention of optical compact discs(CDs)was one of the major landmarks in digital information *** the past half-century,scientists have endeavored to enhance optical storage capacity by improving both optical systems and optical storage materials,as shown in Scheme *** terms of commercial products,the storage capacity has increased from 700 MB(CDs)to 27 GB(Blu-ray discs)by optimizing the optical system based on the same optical storage medium(polycarbonate).To surpass the conventional optical diffraction limit,the optical systems have evolved from traditional lasers to nonlinear two-photon absorption(TPA)and stimulated emission depletion(STED),which has minified the laser spot size from microns to approximately tens of nanometers,marking a remarkable achievement.

关键词： aggregation-induced emission optical storage super disk

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Preserving the literary past, looking to the future: the first hong kong Literature Database

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Journal of Zhejiang University-science A(Applied Physics & Engineering) 2005年第11期6卷 1341-1347页

作者： MA Leo F.H. WONG Rita LAU Paul University Library System The Chinese University of Hong Kong Hong Kong ChinaUniversity Library System The Chinese University of Hong Kong Hong Kong ChinaUniversity Library System The Chinese University of Hong Kong Hong Kong China

In the last two decades of the 20th century, there has been an increasing interest in and emphasis on the study of the hong kong literature in both the academic and general public in hong kong. Recognizing the emergent need of the resources on hong kong literature, the University Library System of the chinese University of hong kong set up the hong kong Literature Database （the “Database”）, which was the first chinese literature database in the Internet in 2000. The paper will examine how the database is constructed using XML technology andometadata schema, The database also employs Unicode UTF-8 as the internal code. A mapping table for traditional and simplified chinese characters was created based on Unihan and is used behind the scene so that a user can either input traditional or simplified chinese characters and retrieval will give both traditional and simplified chinese characters. Currently 65% of journals use OCR technology so that full-text searching is possible. The chinese OCR technology will be examined in greater detail. Special features of the Database such as, page-by-page browse mode, position-highlight for full-page newspaper, linking Table-Of-Contents and book jackets from the Library catalogue, etc. are described. The paper will also bring out the problem of massive downloading and compare the state-of-the-art technology and their shortcomings. This paper shows how the hong kong Literature Database facilitates future collaboration and data exchange by using open standard, shareable structure and the latest technology.

关键词： hong kong Literature hong kong Literature Database XML Metadata schema Database structure UnicodeUTF-8 OCR technology

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Improving open-circuit voltage by a chlorinated polymer donor endows binary organic solar cells efficiencies over 17%

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science China Chemistry 2020年第3期63卷 325-330页

作者： Ruijie Ma Tao Liu Zhenghui Luo Qing Guo Yiqun Xiao Yuzhong Chen Xiaojun Li Siwei Luo Xinhui Lu Maojie Zhang Yongfang Li He Yan Department of Chemistry and hong kong Branch of chinese National Engineering Research Center for Tissue Restoration&Reconstruction Hong Kong University of Science and Technology(HKUST)Clear Water BayKowloonHong KongChina hong kong University of science and Technology-Shenzhen Research Institute Shenzhen 518057China laboratory of Advanced Optoelectronic Materials College of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou 215123China Department of Physics Chinese University of Hong KongNew TerritoriesHong KongChina

Power conversion efficiency(PCE)of single-junction polymer solar cells(PSCs)has made a remarkable breakthrough *** of work was reported to achieve PCEs higher than 16%derived from the PM6:Y6 binary *** further increase the PCEs of binary OSCs incorporating small molecular acceptor(SMA)Y6,we substituted PM6 with PM7 due to the deeper highest occupied molecular orbital(HOMO)of ***,the PM7:Y6 has achieved PCEs as high as 17.0%by the hotcast method,due to the improved open-circuit voltage(VOC).Compared with PM6,the lower HOMO of PM7 increases the gap between ELUMO-donor and EHOMO-acceptor,which is proportional to *** research provides a high PCE for single-junction binary PSCs,which is meaningful for device fabrication related to PM7 and commercialization of PSCs.

关键词： single junction binary system power conversion efficiencies open-circuit voltage

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Facile and rapid fabrication of a novel 3D-printable,visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair

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Bioactive Materials 2024年第7期37卷 439-458页

作者： Xu Zhang Ke Li Chenyang Wang Ying Rao Rocky STuan Dan Michelle Wang Dai Fei Elmer Ker Institute for Tissue Engineering and Regenerative Medicine The Chinese University of Hong KongNew TerritoriesHong Kong SARChina School of Biomedical sciences Faculty of MedicineThe Chinese University of Hong KongNew TerritoriesHong Kong SARChina Center for Neuromusculoskeletal Restorative Medicine Hong Kong Science ParkHong Kong SARChina Ministry of Education Key laboratory for Regenerative Medicine School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongNew TerritoriesHong Kong SARChina Department of Orthopaedics and Traumatology Faculty of MedicineThe Chinese University of Hong KongNew TerritoriesHong Kong SARChina

Facile and rapid 3D fabrication of strong,bioactive materials can address challenges that impede repair of large-to-massive rotator cuff tears including personalized grafts,limited mechanical support,and inadequate tissue ***,we developed a facile and rapid methodology that generates visible light-crosslinkable polythiourethane(PHT)pre-polymer resin(~30 min at room temperature),yielding 3D-printable scaffolds with tendon-like mechanical attributes capable of delivering tenogenic bioactive *** vivo characterization confirmed successful fabrication,robust human supraspinatus tendon(SST)-like tensile properties(strength:23 MPa,modulus:459 MPa,at least 10,000 physiological loading cycles without failure),excellent suture retention(8.62-fold lower than acellular dermal matrix(ADM)-based clinical graft),slow degradation,and controlled release of fibroblast growth factor-2(FGF-2)and transforming growth factor-β3(TGF-β3).In vitro studies showed cytocompatibility and growth factor-mediated tenogenic-like differentiation of mesenchymal stem *** vivo studies demonstrated biocompatibility(3-week mouse subcutaneous implantation)and ability of growth factor-containing scaffolds to notably regenerate at least 1-cm of tendon with native-like biomechanical attributes as uninjured shoulder(8-week,large-to-massive 1-cm gap rabbit rotator cuff injury).This study demonstrates use of a 3D-printable,strong,and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.

关键词： Photo-crosslinkable biomaterials Polyurethane Click reactions 3D-printing Growth factors Rotator cuff tendon tissue engineering

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3D-printed NIR-responsive shape memory polyurethane/magnesium scaffolds with tight-contact for robust bone regeneration

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Bioactive Materials 2022年第10期7卷 218-231页

作者： Yuanchi Zhang Cairong Li Wei Zhang Junjie Deng Yangyi Nie Xiangfu Du Ling Qin Yuxiao Lai Centre for Translational Medicine Research&Development Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenChina University of chinese Academy of sciences ShenzhenChina Key laboratory of Health Informatics Chinese Academy of SciencesShenzhenChina Musculoskeletal Research laboratory Department of Orthopaedics&TraumatologyThe Chinese University of Hong KongHong Kong SARChina CAS-HK joint Lab of biomaterials ShenzhenChina

Patients with bone defects suffer from a high rate of disability and *** contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair *** self-expanding scaffolds were developed to enhance bone integration,the limitations on the high transition temperature and the unsatisfied bioactivity hindered greatly their clinical ***,we report a near-infrared-responsive and tight-contacting scaffold that comprises of shape memory polyurethane(SMPU)as the thermal-responsive matrix and magnesium(Mg)as the photothermal and bioactive component,which fabricated by the low temperature rapid prototyping(LT-RP)3D printing *** designed,due to synergistic effects of the components and the fabrication approach,the composite scaffold possesses a homogeneously porous structure,significantly improved mechanical properties and stable photothermal *** programmed scaffold can be heated to recover under near infrared irradiation in *** 4 wt%Mg,the scaffold has the balanced shape fixity ratio of 93.6%and shape recovery ratio of 95.4%.The compressed composite scaffold could lift a 100 g weight under NIR light,which was more than 1700 times of its own *** results of the push-out tests and the finite element analysis(FEA)confirmed the tight-contacting ability of the SMPU/4 wt%Mg scaffold,which had a signficant enhancement compared to the scaffold without shape memory ***,The osteopromotive function of the scaffold has been demonstrated through a series of in vitro and in vivo *** envision this scaffold can be a clinically effective strategy for robust bone regeneration.

关键词： Shape memory polyurethane Magnesium 3D printing Robust bone regeneration Tight-contact

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