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

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 reconstruction.Although tissue-engineered materials have the ability to repair cartilage,they have weak mechanical characteristics and cannot resist long-term overload.On the other hand,surgery to replace the joint is frequently done to treat significant cartilage deterioration these days.However,the materials that are being used for replacement have high friction coefficients,lack shock absorption functions,and lack cushioning.Further 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 improvements.Based 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 research.For 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 compared.It 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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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 tribology.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 surface.Subsequently,the frictional characteristics were examined in phosphate-buffered saline(PBS)and SF against glass.Angularly 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 specimens.Meanwhile,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 methods.The coefficient of friction(COF)of the prepared cartilage specimens was varied from 0.05 to over 0.3 in PBS.However,a certain group of cartilage specimens exhibited a low COF of less than 0.1 with limited variation.For 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 treatments.This 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 surface.The variation in the COF of the cartilage specimens was suppressed in SF because it had a clear boundary lubrication effect on the cartilage surface.The 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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药学学报:英文版 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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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 joints.AC defects are common in the knees of young and physically active individuals.Because 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 adequately.With 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 behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This 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 repair.Finally,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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Activation of NRF2 by celastrol increases antioxidant functions and prevents the progression of osteoarthritis in mice

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Chinese Journal of Natural Medicines 2024年第2期22卷 137-145页

作者： LIU Mingming GUO Jiatian ZHAO Jing LI Hongye FENG Xiaoxiao LIU Haojun ZHANG Hao JIA Xuejun WEI Rushuai LI Fang CHEN Chong HOU Mingzhuang LV Nanning XU Haiyan Department of human anatomy Xuzhou Medical UniversityXuzhou 221004China Department of Orthopedic Surgery The Affiliated Lianyungang Clinical College of Xuzhou Medical University(The Second People’s Hospital of Lianyungang)Lianyungang 222003China Department of Orthopaedics The First Afliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Institute of Hematology Xuzhou Medical UniversityXuzhou 221004China

Excessive oxidative stress impairs cartilage matrix metabolism balance,significantly contributing to osteoarthritis(OA)development.Celastrol(CSL),a drug derived from Tripterygium wilfordii,has recognized applications in the treatment of cancer and immune system disorders,yet its antioxidative stress mechanisms in OA remain underexplored.This study aimed to substantiate CSL’s chondroprotective effects and unravel its underlying mechanisms.We investigated CSL’s impact on chondrocytes under both normal and inflammatory conditions.In vitro,CSL mitigated interleukin(IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix(ECM)synthesis.In vivo,intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA mice.Mechanistically,it was found that inhibiting nuclear factor erythroid 2-related factor 2(NRF2)abrogated CSL-mediated antioxidative functions and exacerbated the progression of OA.This study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2,offering a novel therapeutic avenue for arthritis therapy.

关键词： Osteoarthritis Celastrol articular cartilage Extracellular matrix NRF2

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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 medicine.As defects progress,they often extend from the cartilage layer to the subchondral bone and ultimately lead to osteoarthritis.Tissue engineering techniques bring new hope for AC regeneration.To meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue,a substantial number of multilayered biomimetic scaffolds have been studied.Ideal multilayered scaffolds should generate zone-specific functional tissue similar to native AC tissue.This 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 manufacturing.The 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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Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis

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Chinese Medical Journal 2012年第5期125卷 843-850页

作者： WEI Zheng-mao DU Xiang-ke HUO Tian-long LI Xu-bin QUAN Guang-nan LI Tian-ran CHENG Jin ZHANG Wei-tao Department of Radiology Peking University People's HospitalBeijing 100044China

Background Quantitative T2 mapping has been a widely used method for the evaluation, of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate liaament transection （ACLTI osteoarthritis.

关键词： magnetic resonance imaging osteoarthritis articular cartilage collagen type Ⅱ

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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 defects.However,great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration.In 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 techniques.The scaffolds successfully achieved hierarchical macro-microporous structures.After adding ECM,WPU scaffolds were markedly optimized in terms of porosity,hydrophilia and bioactive components.Moreover,the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution,adhesion,and proliferation than the WPU scaffolds.Most importantly,the WPU-ECM scaffold could facilitate the production of glycosaminoglycan(GAG)and collagen and the upregulation of cartilage-specific genes.These results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion,proliferation,differentiation,and ECM production.In vivo studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model.Six months after implantation,the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage.In 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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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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Aberrant expression of Twist1 in diseased articular cartilage and a potential role in the modulation of osteoarthritis severity

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Genes & Diseases 2016年第1期3卷 88-99页

作者： Rosa M.Guzzo Farhang Alaee David Paglia Jason D.Gibson Douglas Spicer Hicham Drissi Department of Orthopaedic Surgery UConn HealthFarmingtonCTUSA Stem Cell Institute UConn HealthFarmingtonCTUSA Center for Molecular Medicine Maine Medical Center Research InstituteScarboroughMEUSA Present address:Department of Biomedical Sciences College of Osteopathic MedicineUniversity of New EnglandBiddefordMEUSA

The bHLH transcription factor Twist1 has emerged as a negative regulator of chondrogenesis in skeletal progenitor cells and as an inhibitor of maturation in growth plate chondrocytes.However,its role in articular cartilage remains obscure.Here we examine Twist1 expression during re-differentiation of expanded human articular chondrocytes,the distribution of Twist1 proteins in normal versus OA human articular cartilage,and its role in modulating OA development in mice.High levels of Twist1 transcripts were detected by qPCR analyses of expanded de-differentiated human articular chondrocytes that had acquired mesenchymal-like features.The induction of hallmark cartilage genes by Bmp-2 mediated chondrogenic differentiation was paralleled by the dramatic suppression of Twist1 in vitro.In normal human articular cartilage,Twist1-expressing chondrocytes were most abundant in the superficial zone with little to no expression in the middle and deep zones.However,our analyses revealed a higher proportion of deep zone articular chondrocytes expressing Twist1 in human OA cartilage as compared to normal articular cartilage.Moreover,Twist1 expression was prominent within proliferative cell clusters near fissure sites in more severely affected OA samples.To assess the role of Twist1 in OA pathophysiology,we subjected wild type mice and transgenic mice with gain of Twist1 function in cartilage to surgical destabilization of the medial meniscus.At 12 weeks post-surgery,micro-CT and histological analyses revealed attenuation of the OA phenotype in Twist1 transgenic mice compared to wild type mice.Collectively,the data reveal a role for Twist in articular cartilage maintenance and the attenuation of cartilage degeneration.

关键词： articular cartilage Chondrocytes DMM Osteoarthritis Twist1

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