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13 pages, 3317 KB

Open AccessArticle

Evaluating Feasibility of Human Tissue Engineered Respiratory Epithelium Construct as a Potential Model for Tracheal Mucosal Reconstruction

by Mohd Heikal Mohd Yunus, Zahra Rashidbenam, Mh Busra Fauzi, Ruszymah Bt Hj Idrus and Aminuddin Bin Saim

Molecules 2021, 26(21), 6724; https://doi.org/10.3390/molecules26216724 - 6 Nov 2021

Cited by 7 | Viewed by 2936

Abstract

The normal function of the airway epithelium is vital for the host’s well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in [...] Read more.

The normal function of the airway epithelium is vital for the host’s well-being. Conditions that might compromise the structure and functionality of the airway epithelium include congenital tracheal anomalies, infection, trauma and post-intubation injuries. Recently, the onset of COVID-19 and its complications in managing respiratory failure further intensified the need for tracheal tissue replacement. Thus far, plenty of naturally derived, synthetic or allogeneic materials have been studied for their applicability in tracheal tissue replacement. However, a reliable tracheal replacement material is missing. Therefore, this study used a tissue engineering approach for constructing tracheal tissue. Human respiratory epithelial cells (RECs) were isolated from nasal turbinate, and the cells were incorporated into a calcium chloride-polymerized human blood plasma to form a human tissue respiratory epithelial construct (HTREC). The quality of HTREC in vitro, focusing on the cellular proliferation, differentiation and distribution of the RECs, was examined using histological, gene expression and immunocytochemical analysis. Histological analysis showed a homogenous distribution of RECs within the HTREC, with increased proliferation of the residing RECs within 4 days of investigation. Gene expression analysis revealed a significant increase (p < 0.05) in gene expression level of proliferative and respiratory epithelial-specific markers Ki67 and MUC5B, respectively, within 4 days of investigation. Immunohistochemical analysis also confirmed the expression of Ki67 and MUC5AC markers in residing RECs within the HTREC. The findings show that calcium chloride-polymerized human blood plasma is a suitable material, which supports viability, proliferation and mucin secreting phenotype of RECs, and this suggests that HTREC can be a potential candidate for respiratory epithelial tissue reconstruction. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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11 pages, 3226 KB

Open AccessArticle

Dual Delivery of TGF-β3 and Ghrelin in Microsphere/Hydrogel Systems for Cartilage Regeneration

by Jianjing Lin, Li Wang, Jianhao Lin and Qiang Liu

Molecules 2021, 26(19), 5732; https://doi.org/10.3390/molecules26195732 - 22 Sep 2021

Cited by 25 | Viewed by 3845

Abstract

Articular cartilage (AC) damage is quite common, but due to AC’s poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-β3 [...] Read more.

Articular cartilage (AC) damage is quite common, but due to AC’s poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-β3 (TGF-β3) to enhance cartilage tissue formation and ghrelin synergy TGF-β to significantly enhance the chondrogenic differentiation. The hydrogel and microspheres were characterized in vitro, and the biocompatibility of the system was verified. Double emulsion solvent extraction technology (w/o/w) is used to encapsulate TGF-β3 and ghrelin into microspheres, and these microspheres are encapsulated in a hydrogel to continuously release TGF-β3 and ghrelin. According to the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) in vitro, the concentrations of the two growth factors were optimized to promote cartilage regeneration. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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8 pages, 3503 KB

Open AccessArticle

A pH-Responsive Zwitterionic Polyurethane Prodrug as Drug Delivery System for Enhanced Cancer Therapy

by Qian He, Rui Yan, Wanting Hou, Haibo Wang and Yali Tian

Molecules 2021, 26(17), 5274; https://doi.org/10.3390/molecules26175274 - 31 Aug 2021

Cited by 13 | Viewed by 3466

Abstract

Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a [...] Read more.

Numerous nanocarriers with excellent biocompatibilities have been used to improve cancer therapy. However, nonspecific protein adsorption of nanocarriers may block the modified nanoparticles in tumor cells, which would lead to inefficient cellular internalization. To address this issue, pH-responsive polyurethane prodrug micelles with a zwitterionic segment were designed and prepared. The micelle consisted of a zwitterionic segment as the hydrophilic shell and the drug Adriamycin (DOX) as the hydrophobic inner core. As a pH-responsive antitumor drug delivery system, the prodrug micelles showed high stability in a physiological environment and continuously released the drug under acidic conditions. In addition, the pure polyurethane carrier was demonstrated to be virtually non-cytotoxic by cytotoxicity studies, while the prodrug micelles were more efficient in killing tumor cells compared to PEG-PLGA@DOX. Furthermore, the DOX cellular uptake efficiency of prodrug micelles was proved to be obviously higher than the control group by both flow cytometry and fluorescence microscopy. This is mainly due to the modification of a zwitterionic segment with PU. The simple design of zwitterionic prodrug micelles provides a new strategy for designing novel antitumor drug delivery systems with enhanced cellular uptake rates. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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7 pages, 3052 KB

Open AccessArticle

Simplified Near-Degenerate Four-Wave-Mixing Microscopy

by Jianjun Wang, Xi Zhang, Junbo Deng, Xing Hu, Yun Hu, Jiao Mao, Ming Ma, Yuhao Gao, Yingchun Wei, Fan Li, Zhaohua Wang, Xiaoli Liu, Jinyou Xu and Liqing Ren

Molecules 2021, 26(17), 5178; https://doi.org/10.3390/molecules26175178 - 26 Aug 2021

Cited by 3 | Viewed by 2706

Abstract

Four-wave-mixing microscopy is widely researched in both biology and medicine. In this paper, we present a simplified near-degenerate four-wave-mixing microscopy (SNDFWM). An ultra-steep long-pass filter is utilized to produce an ultra-steep edge on the spectrum of a femtosecond pulse, and a super-sensitive four-wave-mixing [...] Read more.

Four-wave-mixing microscopy is widely researched in both biology and medicine. In this paper, we present a simplified near-degenerate four-wave-mixing microscopy (SNDFWM). An ultra-steep long-pass filter is utilized to produce an ultra-steep edge on the spectrum of a femtosecond pulse, and a super-sensitive four-wave-mixing (FWM) signal can be generated via an ultra-steep short-pass filter. Compared with the current state-of-the-art FWM microscopy, this SNDFWM microscopy has the advantages of simpler experimental apparatus, lower cost, and easier operation. We demonstrate that this SNDFWM microscopy has high sensitivity and high spatial resolution in both nanowires and biological tissues. We also show that the SNDFWM microscopy can achieve an ultra-sensitive detection based on the electron-resonance effect. This method might find an important application in tracking of nano drugs in vivo. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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13 pages, 5374 KB

Open AccessArticle

pH-Responsive Rheological Properties and Microstructure Transition in Mixture of Anionic Gemini/Cationic Monomeric Surfactants

by Maozhang Tian, Xi Chen, Xinyuan Zou, Yuchen Qian, Zhang Liu and Yaxun Fan

Molecules 2021, 26(16), 5013; https://doi.org/10.3390/molecules26165013 - 19 Aug 2021

Cited by 6 | Viewed by 2394

Abstract

Surfactant aggregates have long been considered as a tool to improve drug delivery and have been widely used in medical products. The pH-responsive aggregation behavior in anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C₁₂C₃C₁₂(SO₃ [...] Read more.

Surfactant aggregates have long been considered as a tool to improve drug delivery and have been widely used in medical products. The pH-responsive aggregation behavior in anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C₁₂C₃C₁₂(SO₃)₂) and its mixture with a cationic monomeric surfactant cetyltrimethylammonium bromide (CTAB) have been investigated. The spherical-to-wormlike micelle transition was successfully realized in C₁₂C₃C₁₂(SO₃)₂ through decreasing the pH, while the rheological properties were perfectly enhanced for the formation of wormlike micelles. Especially at 140 mM and pH 6.7, the mixture showed high viscoelasticity, and the maximum of the zero-shear viscosity reached 1530 Pa·s. Acting as a sulfobetaine zwitterionic gemini surfactant, the electrostatic attraction, the hydrogen bond and the short spacer of C₁₂C₃C₁₂(SO₃)₂ molecules were all responsible for the significant micellar growth. Upon adding CTAB, the similar transition could also be realized at a low pH, and the further transformation to branched micelles occurred by adjusting the total concentration. Although the mixtures did not approach the viscosity maximum appearing in the C₁₂C₃C₁₂(SO₃)₂ solution, CTAB addition is more favorable for viscosity enhancement in the wormlike-micelle region. The weakened charges of the headgroups in a catanionic mixed system minimizes the micellar spontaneous curvature and enhances the intermolecular hydrogen-bonding interaction between C₁₂C₃C₁₂(SO₃)₂, facilitating the formation of a viscous solution, which would greatly induce entanglement and even the fusion of wormlike micelles, thus resulting in branched microstructures and a decline of viscosity. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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13 pages, 5316 KB

Open AccessArticle

Peroxidase-Like Platinum Clusters Synthesized by Ganoderma lucidum Polysaccharide for Sensitively Colorimetric Detection of Dopamine

by Xiang Lai, Yu Han, Jie Zhang, Jinyu Zhang, Weifeng Lin, Zhiwei Liu and Longgang Wang

Molecules 2021, 26(9), 2738; https://doi.org/10.3390/molecules26092738 - 6 May 2021

Cited by 22 | Viewed by 3367

Abstract

The sensitive and selective detection of dopamine (DA) is very important for the early diagnosis of DA-related diseases. In this study, we reported the colorimetric detection of DA using Ganoderma lucidum polysaccharide (GLP) stabilized platinum nanoclusters (Pt_n-GLP NCs). When Pt₆₀₀ [...] Read more.

The sensitive and selective detection of dopamine (DA) is very important for the early diagnosis of DA-related diseases. In this study, we reported the colorimetric detection of DA using Ganoderma lucidum polysaccharide (GLP) stabilized platinum nanoclusters (Pt_n-GLP NCs). When Pt₆₀₀-GLP NCs was added, 3,3’,5,5’-tetramethylbenzidine (TMB) was rapidly catalyzed and oxidized to blue oxTMB, indicating the peroxidase-like activity of Pt₆₀₀-GLP NCs. The catalytic reaction on the substrate TMB followed the Michaelis-Menton kinetics with the ping-pong mechanism. The mechanism of the colorimetric reaction was mainly due to the formation of hydroxyl radical (•OH). Furthermore, the catalytic reaction of Pt₆₀₀-GLP NCs was used in the colorimetric detection of DA. The linear range for DA was 1–100 μM and the detection limit was 0.66 μM. The sensitive detection of DA using Pt-GLP NCs with peroxidase-like activity offers a simple and practical method that may have great potential applications in the biotechnology field. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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13 pages, 2327 KB

Open AccessArticle

Clinical-Grade Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Ameliorate the Progression of Osteoarthritis in a Rat Model

by Dan Xing, Kai Wang, Jun Wu, Yu Zhao, Wei Liu, Jiao Jiao Li, Tingting Gao, Deng Yan, Liu Wang, Jie Hao and Jianhao Lin

Molecules 2021, 26(3), 604; https://doi.org/10.3390/molecules26030604 - 24 Jan 2021

Cited by 18 | Viewed by 4207

Abstract

Mesenchymalstem cell (MSC)-based therapy is being increasingly explored in preclinical and clinical studies as a regenerative method for treating osteoarthritis (OA). However, the use of primary MSCs is hampered by a number of limitations, including donor heterogeneity and inconsistent cell quality. Here, we [...] Read more.

Mesenchymalstem cell (MSC)-based therapy is being increasingly explored in preclinical and clinical studies as a regenerative method for treating osteoarthritis (OA). However, the use of primary MSCs is hampered by a number of limitations, including donor heterogeneity and inconsistent cell quality. Here, we tested the therapeutic potential of embryonic stem cell-derived MSCs (ES-MSCs) in anOA rat model. ES-MSCs were generated and identified by morphology, trilineage differentiation and flow cytometry. Sprague Dawley rats were treated with either a single dose (10⁶ cells/rat) of ES-MSCs or with three doses spaced one week apart for each dose, starting at four weeks after anterior cruciate ligament transectionto induce OA. Cartilage quality was evaluated at 6 and 10 weeks after treatment with behavioral analysis, macroscopic examination, and histology. At sixweeks after treatment, the groups treated with both single and repeated doses of ES-MSCs had significantly better modified Mankin scores and International Cartilage Repair Society (ICRS) macroscopic scores in the femoral condyle compared to the control group. At 10 weeks after treatment, the repeated doses group had a significantly better ICRS macroscopic scores in the femoral condyle compared to the single dose and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, along with lower Mankin scores in the repeated doses group. In conclusion, treatment with multiple injections of ES-MSCs can ameliorate OA in a rat model. TheES-MSCs have potential to be considered as a regenerative therapy for OA, and can provide an infinite cellular source. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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11 pages, 3548 KB

Open AccessArticle

Photo-Responsive Polymersomes as Drug Delivery System for Potential Medical Applications

by Wanting Hou, Ruiqi Liu, Siwei Bi, Qian He, Haibo Wang and Jun Gu

Molecules 2020, 25(21), 5147; https://doi.org/10.3390/molecules25215147 - 5 Nov 2020

Cited by 35 | Viewed by 4463

Abstract

Due to a strong retardation effect of o-nitrobenzyl ester on polymerization, it is still a great challenge to prepare amphiphilic block copolymers for polymersomes with a o-nitrobenzyl ester-based hydrophobic block. Herein, we present one such solution to prepare amphiphilic block copolymers with pure [...] Read more.

Due to a strong retardation effect of o-nitrobenzyl ester on polymerization, it is still a great challenge to prepare amphiphilic block copolymers for polymersomes with a o-nitrobenzyl ester-based hydrophobic block. Herein, we present one such solution to prepare amphiphilic block copolymers with pure poly (o-nitrobenzyl acrylate) (PNBA) as the hydrophobic block and poly (N,N’-dimethylacrylamide) (PDMA) as the hydrophilic block using bulk reversible addition-fragmentation chain transfer (RAFT) polymerization of o-nitrobenzyl acrylate using a PDMA macro-RAFT agent. The developed amphiphilic block copolymers have a suitable hydrophobic/hydrophilic ratio and can self-assemble into photoresponsive polymersomes for co-loading hydrophobic and hydrophilic cargos into hydrophobic membranes and aqueous compartments of the polymersomes. The polymersomes demonstrate a clear photo-responsive characteristic. Exposure to light irradiation at 365 nm can trigger a photocleavage reaction of o-nitrobenzyl groups, which results in dissociation of the polymersomes with simultaneous co-release of hydrophilic and hydrophobic cargoes on demand. Therefore, these polymersomes have great potential as a smart drug delivery nanocarrier for controllable loading and releasing of hydrophilic and hydrophobic drug molecules. Moreover, taking advantage of the conditional releasing of hydrophilic and hydrophobic drugs, the drug delivery system has potential use in medical applications such as cancer therapy. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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Review

Jump to: Research

16 pages, 12797 KB

Open AccessReview

Targeted Drug Delivery for the Treatment of Blood Cancers

by Yao Jiang, Weifeng Lin and Linyi Zhu

Molecules 2022, 27(4), 1310; https://doi.org/10.3390/molecules27041310 - 15 Feb 2022

Cited by 33 | Viewed by 6874

Abstract

Blood cancers are a type of liquid tumor which means cancer is present in the body fluid. Multiple myeloma, leukemia, and lymphoma are the three common types of blood cancers. Chemotherapy is the major therapy of blood cancers by systemic administration of anticancer [...] Read more.

Blood cancers are a type of liquid tumor which means cancer is present in the body fluid. Multiple myeloma, leukemia, and lymphoma are the three common types of blood cancers. Chemotherapy is the major therapy of blood cancers by systemic administration of anticancer agents into the blood. However, a high incidence of relapse often happens, due to the low efficiency of the anticancer agents that accumulate in the tumor site, and therefore lead to a low survival rate of patients. This indicates an urgent need for a targeted drug delivery system to improve the safety and efficacy of therapeutics for blood cancers. In this review, we describe the current targeting strategies for blood cancers and recently investigated and approved drug delivery system formulations for blood cancers. In addition, we also discuss current challenges in the application of drug delivery systems for treating blood cancers. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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20 pages, 2081 KB

Open AccessReview

Inorganic Nanomaterial for Biomedical Imaging of Brain Diseases

by Wenxian Du, Lingling Zhou, Qiang Zhang, Xin Liu, Xiaoer Wei and Yuehua Li

Molecules 2021, 26(23), 7340; https://doi.org/10.3390/molecules26237340 - 3 Dec 2021

Cited by 12 | Viewed by 3922

Abstract

In the past few decades, brain diseases have taken a heavy toll on human health and social systems. Magnetic resonance imaging (MRI), photoacoustic imaging (PA), computed tomography (CT), and other imaging modes play important roles in disease prevention and treatment. However, the disadvantages [...] Read more.

In the past few decades, brain diseases have taken a heavy toll on human health and social systems. Magnetic resonance imaging (MRI), photoacoustic imaging (PA), computed tomography (CT), and other imaging modes play important roles in disease prevention and treatment. However, the disadvantages of traditional imaging mode, such as long imaging time and large noise, limit the effective diagnosis of diseases, and reduce the precision treatment of diseases. The ever-growing applications of inorganic nanomaterials in biomedicine provide an exciting way to develop novel imaging systems. Moreover, these nanomaterials with special physicochemical characteristics can be modified by surface modification or combined with functional materials to improve targeting in different diseases of the brain to achieve accurate imaging of disease regions. This article reviews the potential applications of different types of inorganic nanomaterials in vivo imaging and in vitro detection of different brain disease models in recent years. In addition, the future trends, opportunities, and disadvantages of inorganic nanomaterials in the application of brain diseases are also discussed. Additionally, recommendations for improving the sensitivity and accuracy of inorganic nanomaterials in screening/diagnosis of brain diseases. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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19 pages, 3798 KB

Open AccessReview

Recent Advances in Understanding the Role of Cartilage Lubrication in Osteoarthritis

by Yumei Li, Zhongrun Yuan, Hui Yang, Haijian Zhong, Weijie Peng and Renjian Xie

Molecules 2021, 26(20), 6122; https://doi.org/10.3390/molecules26206122 - 11 Oct 2021

Cited by 53 | Viewed by 7881

Abstract

The remarkable lubrication properties of normal articular cartilage play an essential role in daily life, providing almost frictionless movements of joints. Alterations of cartilage surface or degradation of biomacromolecules within synovial fluid increase the wear and tear of the cartilage and hence determining [...] Read more.

The remarkable lubrication properties of normal articular cartilage play an essential role in daily life, providing almost frictionless movements of joints. Alterations of cartilage surface or degradation of biomacromolecules within synovial fluid increase the wear and tear of the cartilage and hence determining the onset of the most common joint disease, osteoarthritis (OA). The irreversible and progressive degradation of articular cartilage is the hallmark of OA. Considering the absence of effective options to treat OA, the mechanosensitivity of chondrocytes has captured attention. As the only embedded cells in cartilage, the metabolism of chondrocytes is essential in maintaining homeostasis of cartilage, which triggers motivations to understand what is behind the low friction of cartilage and develop biolubrication-based strategies to postpone or even possibly heal OA. This review firstly focuses on the mechanism of cartilage lubrication, particularly on boundary lubrication. Then the mechanotransduction (especially shear stress) of chondrocytes is discussed. The following summarizes the recent development of cartilage-inspired biolubricants to highlight the correlation between cartilage lubrication and OA. One might expect that the restoration of cartilage lubrication at the early stage of OA could potentially promote the regeneration of cartilage and reverse its pathology to cure OA. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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24 pages, 6647 KB

Open AccessReview

Advances of Microneedles in Biomedical Applications

by Jie Xu, Danfeng Xu, Xuan Xuan and Huacheng He

Molecules 2021, 26(19), 5912; https://doi.org/10.3390/molecules26195912 - 29 Sep 2021

Cited by 104 | Viewed by 13275

Abstract

A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different shapes (cone and pyramid) and forms (solid, drug-coated, hollow, dissolvable and hydrogel-based microneedles) have been developed. The main objective of [...] Read more.

A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different shapes (cone and pyramid) and forms (solid, drug-coated, hollow, dissolvable and hydrogel-based microneedles) have been developed. The main objective of this review is the applications of microneedles in biomedical areas. Firstly, the classifications and manufacturing of microneedle are briefly introduced so that we can learn the advantages and fabrications of different MNs. Secondly, research of microneedles in biomedical therapy such as drug delivery systems, diagnoses of disease, as well as wound repair and cancer therapy are overviewed. Finally, the safety and the vision of the future of MNs are discussed. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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20 pages, 586 KB

Open AccessReview

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

by Jianjing Lin, Li Wang, Jianhao Lin and Qiang Liu

Molecules 2021, 26(16), 4987; https://doi.org/10.3390/molecules26164987 - 17 Aug 2021

Cited by 22 | Viewed by 5242

Abstract

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a [...] Read more.

Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration. Full article

(This article belongs to the Special Issue Recent Advances in Biomedical Engineering and Molecular Medicine)

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