Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis

Lei, Yiting; Wang, Yuping; Shen, Jieliang; Cai, Zhengwei; Zhao, Chen; Chen, Hong; Luο, Xingguang; Hu, Ning; Cui, Wenguo; Huang, Wei

doi:10.1126/sciadv.abl6449

Cited by 163 publications

(99 citation statements)

References 61 publications

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“…A long-term and sustained drug delivery system based on the microfluid platform will be useful for the clinical application of Ginkgo biloba. The cumulative release time of candidate drugs can be extended to 4 weeks by assembling them into 100-μm-sized gelatin [ 56 ] or hyaluronic acid microspheres [ 57 ]; meanwhile, microsphere-provided superlubricity reduces wear and promotes repair. Despite the novel findings, several limitations should be pointed out.…”

Section: Discussionmentioning

confidence: 99%

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Zhao

Liu

et al. 2022

Arthritis Res Ther

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Background Uncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components. Gingko biloba is a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown. Methods In our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), from Gingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored. Results In interleukin-1β-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB’s chondroprotection with the AMPK-specific inhibitor Compound C abrogated it. Conclusions These results demonstrated that BB extracted from Gingko biloba regulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as a de novo therapeutic insight for OA. Graphical Abstract Schematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herb Gingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Zhao

Liu

et al. 2022

Arthritis Res Ther

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“…ergetic therapy is an emerging platform for the treatment of OA, [3] which can provide long-term joint lubrication without shear thinning [4] and restrain the systematic toxicity from oral administration. [5] The core of synergetic therapy is the intra-articular injection of self-lubricating drug-encapsulated carriers, which are often constructed by porous materials as the core for drug delivery and a surfacefunctionalized soft layer as the shell for lubrication.…”

Section: Doi: 101002/smll202202510mentioning

confidence: 99%

“…Osteoarthritis (OA) is a chronic and progressive joint disease characterized by cartilage destruction, synovial thickening, joint space narrowing, osteophyte, and calcium crystal deposition, which affects hundreds of millions of people worldwide. [ 1,2 ] Synergetic therapy is an emerging platform for the treatment of OA, [ 3 ] which can provide long‐term joint lubrication without shear thinning [ 4 ] and restrain the systematic toxicity from oral administration. [ 5 ] The core of synergetic therapy is the intra‐articular injection of self‐lubricating drug‐encapsulated carriers, which are often constructed by porous materials as the core for drug delivery and a surface‐functionalized soft layer as the shell for lubrication.…”

Section: Introductionmentioning

confidence: 99%

Construction of Core‐Shell NanoMOFs@microgel for Aqueous Lubrication and Thermal‐Responsive Drug Release

Liu

Gong

et al. 2022

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The construction of porous nanocarriers with good lubricating performance and stimuli‐responsive drug release is significant for the synergetic therapy of osteoarthritis (OA). Although metal‐organic framework nanoparticles (nanoMOFs) as carriers can support drug delivery, achieving the synergy of aqueous lubrication and stimuli‐responsive drug release is challenging. In this work, a core‐shell nanoMOFs@poly(N‐isopropylacrylamide) (PNIPAm) microgel hybrid via one‐pot soap‐free emulsion polymerization is developed. Programmable growth of the PNIPAm microgel layer on the surface of nanoMOFs is achieved by tuning the concentration of the monomer and the crosslinker in the reaction. Reversible swelling‐collapsing behaviors of the hybrid are realized by tuning the temperature below and above the lower critical solution temperature. When used as water lubrication additives, the hybrid enables reductions in both the coefficient of friction and wear volume. In vitro thermal‐responsive drug release is demonstrated on the diclofenac sodium‐loaded hybrid by controlling the swelling and collapsing states of the PNIPAm nanolayer. Moreover, the good biocompatibility of the hybrid is verified by culturing toward HeLa and BEAS‐2B cells. These results establish a nanoMOFs@microgel hybrid that can achieve friction and wear reduction and thermal‐responsive drug release.

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“…Delivering HA as micro- and nanogels is another approach to enhance HA retention and joint lubrication [ 64 , 65 , 66 , 67 ]. For instance, injectable and thermoresponsive HA nanogels can be fabricated by conjugating poly(N-isopropylacrylamide) (PNIPAM) chains onto the backbone of HA [ 64 , 66 ].…”

Section: Ha Hydrogels For Joint Lubricationmentioning

confidence: 99%

Engineering Hyaluronic Acid for the Development of New Treatment Strategies for Osteoarthritis

Kim

Guilak

2022

IJMS

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Osteoarthritis (OA) is a degenerative joint disease that is characterized by inflammation of the joints, degradation of cartilage, and the remodeling of other joint tissues. Due to the absence of disease-modifying drugs for OA, current clinical treatment options are often only effective at slowing down disease progression and focus mainly on pain management. The field of tissue engineering has therefore been focusing on developing strategies that could be used not only to alleviate symptoms of OA but also to regenerate the damaged tissue. Hyaluronic acid (HA), an integral component of both the synovial fluid and articular cartilage, has gained widespread usage in developing hydrogels that deliver cells and biomolecules to the OA joint thanks to its biocompatibility and ability to support cell growth and the chondrogenic differentiation of encapsulated stem cells, providing binding sites for growth factors. Tissue-engineering strategies have further attempted to improve the role of HA as an OA therapeutic by developing diverse modified HA delivery platforms for enhanced joint retention and controlled drug release. This review summarizes recent advances in developing HA-based hydrogels for OA treatment and provides additional insights into how HA-based therapeutics could be further improved to maximize their potential as a viable treatment option for OA.

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Injectable hydrogel microspheres with self-renewable hydration layers alleviate osteoarthritis

Cited by 163 publications

References 61 publications

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Construction of Core‐Shell NanoMOFs@microgel for Aqueous Lubrication and Thermal‐Responsive Drug Release

Engineering Hyaluronic Acid for the Development of New Treatment Strategies for Osteoarthritis

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