Functions and applications of extracellular matrix in cartilage tissue engineering

Wang, Chao; Han, Biao; Kwok, Bryan; Han, Lin

doi:10.1016/b978-0-12-823893-6.00004-8

Cited by 3 publications

(3 citation statements)

References 166 publications

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“…Cartilage ECM is mainly composed of GAGs, collagen II fibers and proteoglycans [ 8 , 25 ]. The composition and organization of ECM not only provides a specialized environment for the chondrocytes [ 26 ], but also determines the biomechanical properties of cartilage [ 27 ]. During the cartilage degeneration and OA progression, the ECM are gradually degraded, and components may serve as biomarkers of cartilage degeneration [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair

Uzielienè

Bironaitė

Pachaleva

et al. 2023

IJMS

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The degradation of cartilage, due to trauma, mechanical load or diseases, results in abundant loss of extracellular matrix (ECM) integrity and development of osteoarthritis (OA). Chondroitin sulfate (CS) is a member of the highly sulfated glycosaminoglycans (GAGs) and a primary component of cartilage tissue ECM. In this study, we aimed to investigate the effect of mechanical load on the chondrogenic differentiation of bone marrow mesenchymal stem cells (BM-MCSs) encapsulated into CS-tyramine-gelatin (CS-Tyr/Gel) hydrogel in order to evaluate the suitability of this composite for OA cartilage regeneration studies in vitro. The CS-Tyr/Gel/BM-MSCs composite showed excellent biointegration on cartilage explants. The applied mild mechanical load stimulated the chondrogenic differentiation of BM-MSCs in CS-Tyr/Gel hydrogel (immunohistochemical collagen II staining). However, the stronger mechanical load had a negative effect on the human OA cartilage explants evaluated by the higher release of ECM components, such as the cartilage oligomeric matrix protein (COMP) and GAGs, compared to the not-compressed explants. Finally, the application of the CS-Tyr/Gel/BM-MSCs composite on the top of the OA cartilage explants decreased the release of COMP and GAGs from the cartilage explants. Data suggest that the CS-Tyr/Gel/BM-MSCs composite can protect the OA cartilage explants from the damaging effects of external mechanical stimuli. Therefore, it can be used for investigation of OA cartilage regenerative potential and mechanisms under the mechanical load in vitro with further perspectives of therapeutic application in vivo.

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Section: Discussionmentioning

confidence: 99%

Chondroitin Sulfate-Tyramine-Based Hydrogels for Cartilage Tissue Repair

Uzielienè

Bironaitė

Pachaleva

et al. 2023

IJMS

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“…Both CPC and mAv were uptaken in highest concentrations by the articular cartilage (patellar (PC), femoral (FC), and tibial (TC)) followed by that in menisci tissues (M); the least amount was present in tendons, which is consistent with tissues’ respective GAG content, confirming the dominant role of electrostatic interactions between cationic carriers and the negatively charged aggrecan GAGs (Figure B,C; GAG content in respective tissues is shown in blue). Anterior and posterior cruciate ligaments (ACL and PCL) unexpectedly showed high mAv uptake despite their lower GAG content, which may be due to their close proximity to the site of injection or can be attributed to higher tissue matrix porosity allowing for enhanced solute diffusivity , or mAv’s high hydrophilicity due to the presence of branched PEGs that can further enhance its affinity to intra-tissue hydrophilic macromolecules like aggrecan–GAGs and collagen meshwork . PEGylation is also known to stabilize the protein structure, making it less susceptible to enzymatic degradation and further enhancing its longevity in the complex joint environment .…”

Section: Resultsmentioning

confidence: 99%

Cationic Carrier Mediated Delivery of Anionic Contrast Agents in Low Doses Enable Enhanced Computed Tomography Imaging of Cartilage for Early Osteoarthritis Diagnosis

Zhang

Vedadghavami

et al. 2023

ACS Nano

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Cartilage tissue exhibits early degenerative changes with onset of osteoarthritis (OA). Early diagnosis is critical as there is only a narrow time window during which therapeutic intervention can reverse disease progression. Computed tomography (CT) has been considered for cartilage imaging as a tool for early OA diagnosis by introducing radio-opaque contrast agents like ioxaglate (IOX) into the joint. IOX, however, is anionic and thus repelled by negatively charged cartilage glycosaminoglycans (GAGs) that hinders its intra-tissue penetration and partitioning, resulting in poor CT attenuation. This is further complicated by its short intra-tissue residence time owing to rapid clearance from joints, which necessitates high doses causing toxicity concerns. Here we engineer optimally charged cationic contrast agents based on cartilage negative fixed charge density by conjugating cartilage targeting a cationic peptide carrier (CPC) and multi-arm avidin nanoconstruct (mAv) to IOX, such that they can penetrate through the full thickness of cartilage within 6 h using electrostatic interactions and elicit similar CT signal with about 40× lower dose compared to anionic IOX. Their partitioning and distribution correlate strongly with spatial GAG distribution within healthy and early- to late-stage arthritic bovine cartilage tissues at 50–100× lower doses than other cationic contrast agents used in the current literature. The use of contrast agents at low concentrations also allowed for delineation of cartilage from subchondral bone as well as other soft tissues in rat tibial joints. These contrast agents are safe to use at current doses, making CT a viable imaging modality for early detection of OA and staging of its severity.

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“…This complexity is further enhanced when tissues are subjected to external mechanical stimuli since the ECM can translate them into changes of tissue morphology, strains, and also variations in HP and OS [28]. These changes in HP and OS are intrinsic to the microstructure of the tissues: In most load-bearing tissues, such as cartilage, intervertebral disk, and skin, the ECM consists of a network of collagen fibers embedded in a charged, hydrated matrix of proteoglycan-glycosaminoglycan aggregates and hyaluronic acid [29][30][31]. These negatively charged macromolecules maintain physiological levels of hydration (typically 70-80 % of tissue wet weight) by generating osmotic pressure, and they balance the concentration of dissolved ions (e.g., Na+, Cl-) to satisfy chemical equilibrium and electroneutrality [32].…”

Section: Introductionmentioning

confidence: 99%