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Incorporation of kartogenin and silk fibroin scaffolds promotes rat articular cartilage regeneration through enhancement of antioxidant functions

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Regenerative Biomaterials 2023年第1期10卷 1400-1412页

作者： Zejun Pan Mingzhuang Hou Yijian Zhang Yang Liu Xin Tian Xiayu Hu Xiaoyang Ge Zhijian Zhao Tao Liu Yong Xu Huilin Yang Hao Liu Xuesong Zhu Fan He Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Orthopaedic Institute Suzhou Medical College of Soochow UniversitySoochow UniversitySuzhou 215007China Department of Orthopaedics People’s Hospital of Zhenhai District(Ningbo No.7 Hospital)Ningbo 315202China

Treating articular cartilage defects in patients remains a challenging task due to the absence of blood vessels within the cartilage *** regenerative potential is further compromised by an imbalance between anabolism and catabolism,induced by elevated levels of reactive oxygen ***,the advent of tissue engineering introduces a promising strategy for cartilage regeneration,offering viable solutions such as mechanical support and controlled release of chondrogenic molecules or *** this study,we developed an antioxidant scaffold by incorporating natural silk fibroin(SF)and kartogenin(KGN)-loaded liposomes(SF-Lipo@KGN).The scaffold demonstrated appropriate pore size,connectivity,and water absorption and the sustained release of KGN was achieved through the encapsulation of *** vitro experiments revealed that the SF-Lipo@KGN scaffolds exhibited excellent biocompatibility,as evidenced by enhanced cell adhesion,migration,and proliferation of *** SF-Lipo@KGN scaffolds were found to stimulate cartilage matrix synthesis through the activation of the nuclear factor erythroid-2-related factor 2/heme oxygenase-1 antioxidant signaling *** vivo experiments demonstrated the effective promotion of articular cartilage regeneration by the SF-Lipo@KGN scaffolds,which enhanced extracellular matrix anabolism and restored the intrinsic redox ***,this study successfully developed biomimetic KGN-loaded scaffolds that restore cartilage redox homeostasis,indicating promising prospects for cartilage tissue engineering.

关键词： articular cartilage silk fibroin kartogenin extracellular matrix redox balance NRF2

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Recent Progress in Bionic Hydrogels for articular cartilage:Tribological and Mechanical Characteristics

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Journal of Bionic Engineering 2024年第2期21卷 653-673页

作者： Mohammad Javan Almasi Dangsheng Xiong School of Materials Science and Engineering Nanjing University of Science and TechnologyNanjing210094China

cartilage regeneration and repair are considered clinical challenges since cartilage has limited capability for *** tissue-engineered materials have the ability to repair cartilage,they have weak mechanical characteristics and cannot resist long-term *** the other hand,surgery to replace the joint is frequently done to treat significant cartilage deterioration these ***,the materials that are being used for replacement have high friction coefficients,lack shock absorption functions,and lack *** research on natural articular cartilage structure and function may lead to bionic hydrogels,which have suitable physicochemical and biological characteristics(e.g.,tribological and mechanical properties and the ability to support loadbearing capability),but need *** on their tribological and mechanical characteristics,the current review highlights the most recent advancements of bionic hydrogels used for articular cartilage,highlighting both the field's recent progress and its potential for future *** this reason,firstly,some important property improvement methods of bionic hydrogels are discussed and then,the recent findings of various research on the making of those bionic materials are provided and *** seems that by using some modifications such as product design,surface treatments,animal tests,controlling the isoelectric point of hydrogels,and computer simulation,the intended mechanical and tribological characteristics of natural articular cartilage may be attained by the bionic hydrogels.

关键词： Bionic hydrogel articular cartilage Mechanical property Tribological property Lubrication

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Effect of Rotational and Sliding Motions on Friction and Degeneration of articular cartilage under Dry and Wet Friction

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Journal of Bionic Engineering 2015年第3期12卷 464-472页

作者： Ahmet C. Cilingir Department of Mechanical Engineering Sakarya University 54187 Sakatya Turkey

Understanding the tribological properties of articular cartilage allows scientists to evaluate degenerative joint diseases and develop new treatment techniques. The objectives of this study are to demonstrate the detrimental effect of rotational motion under both dry and wet friction and to evaluate the friction and wear behavior of bovine articular cartilage with sliding and rotational testing configurations that represent fluid film and boundary lubrication mechanisms, respectively. The articular cartilage pin and plate samples were harvested from healthy adult bovine and then tested on a self-made friction and wear simulator. cartilage samples were subjected to sliding and rotational motions under constant load. Friction coefficients and wear factors were calculated under three conditions： using bovine serum, phosphate buffered saline and with no lubricant present. The friction coefficient and wear factor of the articular cartilage were significantly increased with rotational motion under both dry and wet friction. Using bovine serum as lubricant in the sliding testing configuration the friction coefficient and wear factor of articular cartilage were both decreased. A similar decrease in the tribological properties of cartilage was initially observed for the rotational testing configuration with bovine serum; however, the friction coefficient and wear factor were increased after 150,000 cycles. In the absence of lubricant, the articular cartilage was entirely worn on contact area in both sliding and rotational testing configurations. Bovine serum proved an effective fluid film lubricant for articular cartilage surfaces.

关键词： articular cartilage rotational motion sliding motion dry friction wet friction wear

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Experimental study on boundary lubricity of superficial area of articular cartilage and synovial fluid

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Friction 2024年第5期12卷 981-996页

作者： Wenxiao LI Takehiro MORITA Yoshinori SAWAE Departure of Mechanical Engineering Kyushu UniversityFukuoka8190395Japan International Institute for Carton-Neutral Energy Research Kyushu UniversityFukuoka8190395Japan Advanced Research Center for Biomechanics Kyushu UniversityFukuoka8190395Japan

The boundary lubrication mechanism at the articulating surface of natural synovial joints has been the subject of much discussion in *** this study,to elucidate the lubricating function of the superficial area of articular cartilage and synovial fluid(SF),cartilage specimens were processed with four different treatments:gentle and severe washing with detergent,incubation in NaCl solution,and trypsin digestion to selectively remove certain constituents from the cartilage ***,the frictional characteristics were examined in phosphate-buffered saline(PBS)and SF against *** reciprocating sliding tests with a spherical glass probe and square articular cartilage specimens were performed at low contact loads in the mN range to extract the frictional behavior in the superficial area of the cartilage ***,the cartilage surface was observed to confirm the effects of treatments on the morphology of the cartilage surface using a fluorescence microscope and water-immersion *** coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in ***,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited *** the low COF group of specimens,all four treatments increased the COF in PBS to different extents,and fluorescence microscopy revealed that the integrity of the cartilage surface was deteriorated by *** means that the intact cartilage surface had lubricating constituents to maintain low friction,and the removal of such constituents resulted in the loss of the intrinsic boundary lubricity of the cartilage *** variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage *** lubricating effect of SF could be confirmed even after degenerative treatment.

关键词： articular cartilage synovial fluid the uppermost superficial layer boundary lubrication

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Advancing drug delivery to articular cartilage:From single to multiple strategies

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4127-4148页

作者： Tianyuan Zhao Xu Li Hao Li Haoyuan Deng Jianwei Li Zhen Yang Songlin He Shuangpeng Jiang Xiang Sui Quanyi Guo Shuyun Liu Institute of Orthopedics The First Medical CenterChinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLABeijing 100853China School of Medicine Nankai UniversityTianjin 300071China Musculoskeletal Research Laboratory Department of Orthopedics&TraumatologyThe Chinese University of Hong Kong999077Hong KongChina Arthritis Clinic&Research Center Peking University People’s HospitalPeking UniversityBeijing 100044China Department of Joint Surgery Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China

articular cartilage(AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis(OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intraarticular drug delivery systems(DDSs) in the future.

关键词： Drug delivery systems articular cartilage cartilage injury Osteoarthritis cartilage regeneration Multiple drug delivery strategy Biomaterials Therapeutic factors

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Advances and prospects in biomimetic multilayered scaffolds for articular cartilage regeneration

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Regenerative Biomaterials 2020年第6期7卷 527-542页

作者： Liwei Fu Zhen Yang Cangjian Gao Hao Li Zhiguo Yuan Fuxin Wang Xiang Sui Shuyun Liu Quanyi Guo School of Medicine Nankai UniversityNo.94 Weijin RoadNankai DistrictTianjin 300071China Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLAInstitute of OrthopedicsThe First Medical CenterChinese PLA General HospitalNo.28 Fuxing RoadHaidian DistrictBeijing 100853China Department of Bone and Joint Surgery Renji HospitalSchool of MedicineShanghai Jiaotong UniversityNo.160 Pujian RoadPudong New DistrictShanghai 200127China

Due to the sophisticated hierarchical structure and limited reparability of articular cartilage(AC),the ideal regeneration of AC defects has been a major challenge in the field of regenerative *** defects progress,they often extend from the cartilage layer to the subchondral bone and ultimately lead to *** engineering techniques bring new hope for AC *** meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue,a substantial number of multilayered biomimetic scaffolds have been *** multilayered scaffolds should generate zone-specific functional tissue similar to native AC *** review focuses on the current status of multilayered scaffolds developed for AC defect repair,including design strategies based on the degree of defect severity and the zone-specific characteristics of AC tissue,the selection and composition of biomaterials,and techniques for design and *** challenges and future perspectives of biomimetic multilayered scaffold strategies for AC regeneration are also discussed.

关键词： biomimetic multilayered scaffold articular cartilage regeneration tissue engineering osteochondral

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Influence of synovia constituents on tribological behaviors of articular cartilage

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Friction 2013年第2期1卷 150-162页

作者： Teruo MURAKAMI Seido YARIMITSU Kazuhiro NAKASHIMA Yoshinori SAWAE Nobuo SAKAI Research Center for Advanced Biomechanics Kyushu University744 MotookaNishi-kuFukuoka819-0395Japan Department of Mechanical Engineering Faculty of EngineeringKyushu University744 MotookaNishi-kuFukuoka819-0395Japan Department of Applied Science for Integrated System Engineering Graduate School of EngineeringKyushu Institute of Technology1-1SensuichoTobata-kuKitakyushu804-8550Japan

The extremely low friction and minimal wear in natural synovial joints appear to be established by effective lubrication mechanisms based on appropriate combination of articular cartilage and synovial *** complex structure of cartilage composed of collagen and proteoglycan with high water content contributes to high load-carrying capacity as biphasic materials and the various constituents of synovial fluid play important roles in various lubrication ***,the detailed differences in functions of the intact and damaged cartilage tissues,and the interaction or synergistic action of synovia constituents with articular cartilage have not yet been *** this study,to examine the roles of synovia constituents and the importance of cartilage surface conditions,the changes in friction were observed in the reciprocating tests of intact and damaged articular cartilage specimens against glass plate lubricated with lubricants containing phospholipid,protein and/or hyaluronic acid as main constituents in synovial *** effectiveness of lubricant constituents and the influence of cartilage surface conditions on friction are *** addition,the protectiveness by synovia constituents for intact articular cartilage surfaces is evaluated.

关键词： articular cartilage synovial fluid synovial joint lubrication biotribology

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Permeation of dimethyl sulfoxide into articular cartilage at subzero temperatures

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第3期13卷 213-220页

作者： Shao-zhi ZHANG Xiao-yi YU Guang-ming CHEN Institute of Refrigeration and Cryogenics Zhejiang University Hangzhou 310027 China

Osteochondral allografting has been proved to be a useful method to treat diseased or damaged areas of joint surfaces. Operational long-term stocks of grafts which supply a buffer between procurement and utilization would contribute to the commercialization or industrialization of this technology. Vitrification has been thought to be a promising method for successful preservation of articular cartilage （AC）, but high concentration cryoprotectants （CPAs） are used which may cause high cellular toxicity. An effective way to reduce CPA toxioity is to increase CPA concen- tration gradually while the temperature is lowered. Understanding the mechanism of （31~A permeation at subzero temperatures is important for designing the cryopreservation protocol. In this research, the permeation of dimethyl sulfoxide （MezSO） in ovine AC at subzero temperatures was studied experimentally. Pretreated AC discs were ex- posed in Me2SO solutions for different time （0, 5, 15, 30, 50, 80, and 120 min） at three temperature levels （-10, -20, and -30℃）. The Me2SO concentration within the tissue was determined by ultraviolet （UV） spectrophotometry. The diffusion coefficients were estimated to be 0.85×10-6, 0.48×10-8, and 0.27×10-6 cm2/s at -10, -20, and -,30℃, respectively, and the corresponding activation energy was 29.23 kJ/mol. Numerical simulation was performed to com- pare two Me2SO addition protocols, and the results demonstrated that the total loading duration could be effectively reduced with the knowledge of permeation kinetics.

关键词： articular cartilage Vitrification Dimethyl sulfoxide Permeation Diffusion coefficient Subzero temperature

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Functionalized Hydrogels for articular cartilage Tissue Engineering

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Engineering 2022年第6期8卷 71-90页

作者： Liangbin Zhou Peng Guo Matteo D’Este Wenxue Tong Jiankun Xu Hao Yao Martin J.Stoddart Gerjo J.V.M.van Osch Kevin Ki-Wai Ho Zhen Li Ling Qin Musculoskeletal Research Laboratory of Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Innovative Orthopaedic Biomaterials and Drug Translational Research Laboratory Li Ka Shing Institute of Health SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China AO Research Institute Davos DavosCH 7270Switzerland Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury Department of Orthopaedic SurgeryThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen 518000China Department of Orthopaedics and Sports Medicine&Department of Otorhinolaryngology Erasmus MCUniversity Medical CenterRotterdam 3000 CAthe Netherlands f Department of Biomechanical EngineeringDelft University of TechnologyDelft 2600 AAthe Netherlands Centre for Translational Medicine Research and Development Shenzhen Institute of Advanced TechnologyThe Chinese Academy of SciencesShenzhen 518000China

articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial *** defects are common in the knees of young and physically active *** of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage *** rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating *** can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of *** article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC ***,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.

关键词： articular cartilage Functionalized hydrogels cartilage repair cartilage tissue engineering Clinical translation

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Hierarchical macro-microporous WPU-ECM scaffolds combined with Microfracture Promote in Situ articular cartilage Regeneration in Rabbits

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Bioactive Materials 2021年第7期6卷 1932-1944页

作者： Mingxue Chen YangYang Li Shuyun Liu Zhaoxuan Feng Hao Wang Dejin Yang Weimin Guo Zhiguo Yuan Shuang Gao Yu Zhang Kangkang Zha Bo Huang Fu Wei Xinyu Sang Qinyu Tian Xuan Yang Xiang sui Yixin Zhou Yufeng Zheng Quanyi Guo Department of Orthopaedic Surgery Peking University Fourth School of Clinical MedicineBeijing Jishuitan HospitalNo.31 Xinjiekou East StreetXicheng DistrictBeijing100035People’s Republic of China Institute of Orthopedics Chinese PLA General HospitalBeijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma&War Injuries PLANo.28 Fuxing RoadHaidian DistrictBeijing100853People’s Republic of China Academy for Advanced Interdisciplinary Studies Peking UniversityNo.5 Yiheyuan RoadHaidian DistrictBeijing100871People’s Republic of China School of Material Science and Engineering University of Science and Technology BeijingNo.30 Xueyuan RoadHaidian DistrictBeijing100083People’s Republic of China Department of Bone and Joint Surgery The Affiliated Hospital of Southwest Medical UniversityNo.25 Taiping RoadLuzhou646000People’s Republic of China Department of Materials Science and Engineering College of EngineeringPeking UniversityNo.5 Yiheyuan RoadHaidian DistrictBeijing100871China

Tissue engineering provides a promising avenue for treating cartilage ***,great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and *** this study,decellularized cartilage extracellular matrix(ECM)and waterborne polyurethane(WPU)were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing(LDM)system,which combines rapid deposition manufacturing with phase separation *** scaffolds successfully achieved hierarchical macro-microporous *** adding ECM,WPU scaffolds were markedly optimized in terms of porosity,hydrophilia and bioactive ***,the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution,adhesion,and proliferation than the WPU *** importantly,the WPU-ECM scaffold could facilitate the production of glycosaminoglycan(GAG)and collagen and the upregulation of cartilage-specific *** results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion,proliferation,differentiation,and ECM *** vivo studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit *** months after implantation,the repaired cartilage showed a similar histological structure and mechanical performance to that of normal *** conclusion,the hierarchical macro-microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

关键词： Extracellular matrix Waterborne polyurethane Low-temperature deposition manufacturing articular cartilage Tissue engineering

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