ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis

Li, Yitong; Cao, Jie; Han, Shangcong; Liang, Yan; Zhang, Tingting; Zhao, Han; Wang, Yunlong; Sun, Yong

doi:10.1080/21691401.2018.1452752

Cited by 48 publications

(34 citation statements)

References 31 publications

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“…The interaction of ECM components forms network structure, which provides nutrition for chondrocyte, and affects various biological functions of chondrocyte through signal transduction system. When OA occurs, the synthesis and degradation of ECM are unbalanced [14,15]. Many microRNAs (miRNAs) are tissue-specific or developmental stage-specific and are associated with diseases such as tumors, lymphomas, viral infections and orthopedic diseases [16].…”

Section: Introductionmentioning

confidence: 99%

miR-122/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis

et al. 2020

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Background/Aims: MicroRNAs (miRNAs) are involved in the pathogenesis of osteoarthritis (OA). The present study aimed to investigate the potential function of miR-122 in the development of OA and its potential molecular mechanisms. Methods: The expression of miR-122, silent information regulator 1 (SIRT1), collagen II, aggrecan, matrix metalloproteinase (MMP) 13 (MMP13) and ADAMTS4 in OA cartilage was detected by RT-qPCR. Target gene prediction and screening, luciferase reporter assay were used to verify downstream target genes of miR-122. Results: Compared with osteonecrosis, the expression of miR-122 was significantly increased in OA cartilage, while the expression of SIRT1 was significantly decreased. Overexpression of miR-122 increased the expression of extracellular matrix (ECM) catabolic factors, for example disintegrins, MMPs and metalloproteinases with platelet reaction protein motifs, and inhibited the expression of synthetic metabolic genes such as collagen II and aggregating proteoglycan. Inhibition of miR-122 expression had the opposite effect. Furthermore, SIRT1 was identified as a direct target of miR-122. SIRT1 was significantly inhibited by miR-122 overexpression. Knockdown of SIRT1 reversed the degradation of chondrocyte ECM by miR-122 inhibitors. Conclusion: The miR-122/SIRT1 axis can regulate the degradation of ECM in OA, thus providing new insights into the treatment of OA.

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Section: Introductionmentioning

confidence: 99%

miR-122/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis

et al. 2020

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“…Several biomaterials have been employed for developing injectable hydrogels to mimic the biological cues of native ECM, however, they cannot reproduce the complex functions of natural ECM. Recently, increasing attention has been paid to the development of tissue‐derived ECM as a biomaterial to generate injectable hydrogels, some of them based on dermal ECM or in hybrid injectable hydrogels of thermosensitive soluble ECM and methylcellulose as stem cell delivery systems in skin wound treatments …”

Section: Therapeutic Strategies For Skin Regenerationmentioning

confidence: 99%

Therapeutic strategies for skin regeneration based on biomedical substitutes

Chocarro‐Wrona

López‐Ruiz

Perán

et al. 2019

Acad Dermatol Venereol

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Regenerative medicine and tissue engineering (TE) have experienced significant advances in the development of in vitro engineered skin substitutes, either for replacement of lost tissue in skin injuries or for the generation of in vitro human skin models to research. However, currently available skin substitutes present different limitations such as expensive costs, abnormal skin microstructure and engraftment failure. Given these limitations, new technologies, based on advanced therapies and regenerative medicine, have been applied to develop skin substitutes with several pharmaceutical applications that include injectable cell suspensions, cell‐spray devices, sheets or 3Dscaffolds for skin tissue regeneration and others. Clinical practice for skin injuries has evolved to incorporate these innovative applications to facilitate wound healing, improve the barrier function of the skin, prevent infections, manage pain and even to ameliorate long‐term aesthetic results. In this article, we review current commercially available skin substitutes for clinical use, as well as the latest advances in biomedical and pharmaceutical applications used to design advanced therapies and medical products for wound healing and skin regeneration. We highlight the current progress in clinical trials for wound healing as well as the new technologies that are being developed and hold the potential to generate skin substitutes such as 3D bioprinting‐based strategies.

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“…Drug delivery systems provide an opportunity to incorporate therapeutics into a material that can provide sustained release into the joint [24]. A number of drug delivery systems for intra-articular injection have been developed, including liposomes [25], particles [26][27][28], hydrogels [29][30][31], and dendrimers [32]. Particles in particular have been shown to afford prolonged release in the joint over a period of months.…”

Section: Introductionmentioning

confidence: 99%

GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery

et al. 2020

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Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor δ (PPARδ) in cartilage may attenuate the development or progression of OA. PPARδ antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young’s moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy.

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ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis

Cited by 48 publications

References 31 publications

miR-122/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis

miR-122/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis

Therapeutic strategies for skin regeneration based on biomedical substitutes

GSK3787-Loaded Poly(Ester Amide) Particles for Intra-Articular Drug Delivery

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