Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon‐To‐Bone Healing

Song, Wei; Ma, Zhijie; Wang, Xin; Wang, Yifei; Wu, Di; Wang, Chongyang; He, Dan; Kong, Lingzhi; Yu, Weilin; Li, Jiao Jiao; Li, Haiyan; He, Yaohua

doi:10.1002/advs.202304090

Cited by 7 publications

(1 citation statement)

References 96 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dates from healing mouse flexor tendons has demonstrated that overactivation of the NF-κB signaling pathway enhanced the presence of proinflammatory macrophages at the injured area, resulting in elevated formation of scar tissue and disrupting the mechanical properties of the healing tendon ( 63 ). Additionally, an experimental study in a rat rotator cuff healing model displayed that inhibiting the NF-κB signaling pathway, deceased macrophage polarization toward M1 macrophages and thereby reduced the production of excessive inflammatory factors and finally provoked the regenerative potential of injured tissue ( 64 ). Previous reports have indicated that microRNAs (miRNAs) primarily function as a silencer of coding genes and that the expression of miRNAs is thought to play a significant role in injured tissue’s healing process.…”

Section: The Mechanisms Of Nf-κb In Tendon Fibrotic Scar Healing Adhe...mentioning

confidence: 99%

The roles and mechanisms of the NF-κB signaling pathway in tendon disorders

Li,

Luo

et al. 2024

Front. Vet. Sci.

View full text Add to dashboard Cite

Both acute and chronic tendon injuries are the most frequently occurring musculoskeletal diseases in human and veterinary medicine, with a limited repertoire of successful and evidenced-based therapeutic strategies. Inflammation has been suggested as a key driver for the formation of scar and adhesion tissue following tendon acute injury, as well as pathological alternations of degenerative tendinopathy. However, prior efforts to completely block this inflammatory process have yet to be largely successful. Recent investigations have indicated that a more precise targeted approach for modulating inflammation is critical to improve outcomes. The nuclear factor-kappaB (NF-κB) is a typical proinflammatory signal transduction pathway identified as a key factor leading to tendon disorders. Therefore, a comprehensive understanding of the mechanism or regulation of NF-κB in tendon disorders will aid in developing targeted therapeutic strategies for human and veterinary tendon disorders. In this review, we discuss what is currently known about molecular components and structures of basal NF-κB proteins and two activation pathways: the canonical activation pathway and the non-canonical activation pathway. Furthermore, we summarize the underlying mechanisms of the NF-κB signaling pathway in fibrosis and adhesion after acute tendon injury, as well as pathological changes of degenerative tendinopathy in all species and highlight the effect of targeting this signaling pathway in tendon disorders. However, to gain a comprehensive understanding of its mechanisms underlying tendon disorders, further investigations are required. In the future, extensive scientific examinations are warranted to full characterize the NF-κB, the exact mechanisms of action, and translate findings into clinical human and veterinary practice.

show abstract

Section: The Mechanisms Of Nf-κb In Tendon Fibrotic Scar Healing Adhe...mentioning

confidence: 99%

The roles and mechanisms of the NF-κB signaling pathway in tendon disorders

Li,

Luo

et al. 2024

Front. Vet. Sci.

View full text Add to dashboard Cite

show abstract

Hierarchical Chiral Calcium Silicate Hydrate Films Promote Vascularization for Tendon‐to‐Bone Healing

Cai,

Qu,

Song

et al. 2024

Advanced Materials

Self Cite

View full text Add to dashboard Cite

Revascularization after rotator cuff repair is crucial for tendon‐to‐bone healing. The chirality of materials has been reported to influence their performance in tissue repair. However, data on the use of chiral structures to optimize biomaterials as a revascularization strategy remain scarce. Here, we develop calcium silicate hydrate (CSO) films with hierarchical chirality on the atomic to micrometer scale. Interestingly, levorotatory CSO (L‐CSO) films promote the migration and angiogenesis of endothelial cells, whereas dextral and racemic CSO films do not induce the same effect. Molecular analysis demonstrate that L‐chirality can be recognized by integrin receptors and lead to the formation of focal adhesion, which activates mechanosensitive ion channel transient receptor potential vanilloid 4 to conduct Ca2+ influx. Consequently, the phosphorylation of serum response factor is biased by Ca2+ influx to promote the vascular endothelial growth factor receptor 2 signaling pathway, resulting in enhanced angiogenesis. After implanted in a rat rotator cuff tear model, L‐CSO films strongly enhance vascularization at the enthesis, promoting collagen maturation, increasing bone and fibrocartilage formation, and eventually improving the biomechanical strength. This study reveals the mechanism through which chirality influences angiogenesis in endothelial cells and provides a critical theoretical foundation for the clinical application of chiral biomaterials.This article is protected by copyright. All rights reserved

show abstract

Circadian Rhythm‐Regulated ADSC‐Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon‐to‐Bone Healing

Song,

Guo,

Liu

et al. 2024

Advanced Materials

View full text Add to dashboard Cite

Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon‐to‐bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon‐to‐bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose‐derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm‐regulated sEVs (CR‐sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR‐sEVs (CR‐sEVs/MN) at the tendon‐to‐bone junction, incorporating tendon‐derived decellularized extracellular matrix in the base to facilitate tendon repair. CR‐sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR‐sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon‐to‐bone healing in clinical settings.

show abstract

Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon‐To‐Bone Healing

Cited by 7 publications

References 96 publications

The roles and mechanisms of the NF-κB signaling pathway in tendon disorders

The roles and mechanisms of the NF-κB signaling pathway in tendon disorders

Hierarchical Chiral Calcium Silicate Hydrate Films Promote Vascularization for Tendon‐to‐Bone Healing

Circadian Rhythm‐Regulated ADSC‐Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon‐to‐Bone Healing

Contact Info

Product

Resources

About