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

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(31)

Published: May 20, 2024

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 chiral structures optimize biomaterials as a revascularization strategy remain scarce. Here, calcium silicate hydrate (CSO) films with hierarchical atomic micrometer scale are developed. Interestingly, levorotatory CSO (L-CSO) promote migration and angiogenesis endothelial cells, whereas dextral racemic do not induce same effects. Molecular analysis demonstrates that L-chirality can be recognized by integrin receptors leads formation focal adhesion, which activates mechanosensitive ion channel transient receptor potential vanilloid 4 conduct Ca

Language: Английский

---

Advances and challenges in biomaterials for tendon and enthesis repair

Bioactive Materials, Journal Year: 2025, Volume and Issue: 47, P. 531 - 545

Published: Feb. 20, 2025

Language: Английский

---

Leptin Enhances M1 Macrophage Polarization and Impairs Tendon-Bone Healing in Rotator Cuff Repair: A Rat Model

Clinical Orthopaedics and Related Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Background Rotator cuff tears are common, affecting more than 60% of individuals older 80 years, and they have been implicated in 70% patients with shoulder pain. M1 polarization-related inflammation has reported to be associated poor healing outcomes rotator injury, leptin, an adipokine, a potential activator inflammation. However, whether leptin affects repair remains unknown. Questions/purposes Using vitro cell experiments vivo rat tear model, we therefore asked: (1) Does promote the polarization macrophages vivo? (2) impair biomechanical strength, histologic structure tendon-bone interface, bone mineral density (BMD), or gait scenario? (3) by upregulating tumor necrosis factor (TNF) pathway? Methods The impact on macrophage was determined reverse transcription–polymerase chain reaction (RT-PCR), Western blot test, immunofluorescence staining. effect assessed model comparing group suture terms gait, tensile BMD. In experiments, 8-week-old male Sprague Dawley rats were used, adapting previously developed model. supraspinatus tendon resected from greater tuberosity bilaterally, then secured its anatomical footprint using transosseous single-row technique. total, 30 randomized into two groups (suture, leptin) drawing lots (15 each group). They at 2, 4, 8 weeks after surgery. group, 100 µL normal saline injected subacromial space deltoid muscle restitched original position. solution (200 ng/mL) Biomechanical properties including maximal failure load, stiffness, stress assess strength 4 Histologic staining conducted compare interface between treatment groups. Micro-MRI micro-CT assessments overall outcome BMD Gait analysis stride length Finally, explore underlying mechanism effects Necrostatin-1 (Nec-1) used block TNF signaling pathway study, RT-PCR mechanism. Results Leptin enhanced LPS-induced vitro, showing increased gene expression CD86, Nos2, TNF-α as well protein TNF-α, interleukin-6 (IL-6), inducible NO synthase (iNOS). showed that promoted. At 2 postoperatively, there cells (53 ± 5 versus 77 8, mean difference 24 [95% confidence interval (CI) 11 37]; p = 0.002), although proportion (ratio number total macrophages) not higher (18.6% 2.9% 21.5% 1.7%, CI -2.8% 8.7%]; 0.36). exhibited (31 50 6, 19 6 32]; 0.008) (16.4% 2.6% 23.0% 3.0%, 6.6% 0.8% 12.4%]; 0.03). impaired healing. both different load (12.7 1.6 N 12.4 1.8 N, -0.3 -2.6 1.8]; 0.91), stiffness (5.1 0.7 N/mm 4.6 0.8 N/mm, -0.5 -1.3 0.5]; 0.44), (2.0 0.3 2.0 , 0.0 -0.4 0.4]; 0.99). worse (17.6 1.4 14.1 -3.5 -5.7 -1.3]; (7.0 0.6 5.2 -1.8 -2.7 -0.9]; < 0.001), (3.4 2.8 0.4 -0.6 -1.0 -0.2]; 0.007). staining, image assessments, also demonstrated process. upregulated molecules pathway, CCL2 receptor-interacting kinase 1 (RIPK1), markers, such Nos2; addition Nec-1 neutralized polarization, reducing blocking RIPK. similar trends. Conclusion Based results this appears tear, upregulate polarization. Clinical Relevance Obesity fatty infiltration tears. adipose factor, explored. Future studies might focus developing novel approaches improve obesity targeting aid biomaterials.

Language: Английский

---

Advantages and disadvantages of various hydrogel scaffold types: A research to improve the clinical conversion rate of loaded MSCs-Exos hydrogel scaffolds

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117386 - 117386

Published: Sept. 6, 2024

Language: Английский

---

Silencing BMAL1 promotes M1/M2 polarization through the LDHA/lactate axis to promote GBM sensitivity to bevacizumab

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 134, P. 112187 - 112187

Published: May 11, 2024

Language: Английский

---

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

Advanced Science, Journal Year: 2023, Volume and Issue: 10(34)

Published: Oct. 22, 2023

Osteoporotic tendon-to-bone healing (TBH) after rotator cuff repair (RCR) is a significant orthopedic challenge. Considering the aligned architecture of tendon, inflammatory microenvironment at injury site, and need for endogenous cell/tissue infiltration, there an imminent ideal scaffold to promote TBH that has architecture, ability modulate inflammation, macroporous structure. Herein, novel hydrogel comprising sodium alginate/hyaluronic acid/small extracellular vesicles from adipose-derived stem cells (sEVs) (MHA-sEVs) with immunomodulatory fabricated. When implanted subcutaneously, MHA-sEVs significantly improve cell infiltration tissue integration through its applied osteoporotic RCR model, by improving tendon while enhancing bone regeneration modulating inflammation. Notably, biomechanical strength approximately two times higher than control group, indicating great potential in reducing postoperative retear rates. Further cell-hydrogel interaction studies reveal alignment microfiber gels induces tenogenic differentiation tendon-derived cells, sEVs mitochondrial dysfunction M1 macrophages (Mφ) inhibit Mφ polarization toward via nuclear factor-kappaB (NF-κb) signaling pathway. Taken together, provide promising strategy future clinical application promoting TBH.

Language: Английский

---

An injectable antibacterial wet-adhesive for meniscal cartilage regeneration via immune homeostasis mediated by SMSC-derived extracellular vesicles

Composites Part B Engineering, Journal Year: 2024, Volume and Issue: 291, P. 111970 - 111970

Published: Nov. 12, 2024

Language: Английский

---

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

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

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

Language: Английский

---

The P2X7R/NLRP3 inflammasome axis suppresses enthesis regeneration through inflammatory and metabolic macrophage-stem cell cross-talk

Science Advances, Journal Year: 2025, Volume and Issue: 11(17)

Published: April 25, 2025

The regeneration of the enthesis remains a formidable challenge in regenerative medicine. However, key regulators underlying unsatisfactory remain poorly understood. This study reveals that purinergic receptor P2X7 (P2X7R)/Nod-like family protein 3 (NLRP3) inflammasome axis suppresses by amplifying IL-1β–mediated inflammatory cross-talk and suppressing docosatrienoic acid (DTA) metabolic cross-talk. NLRP3 inflammasomes were activated macrophages following injury, thereby impairing histological functional recovery injured enthesis. Single-cell RNA sequencing (scRNA-seq) indicated Nlrp3 knockout attenuated pathological inflammation ameliorated detrimental effects IL-1β signaling Furthermore, suppressed secretion anti-inflammatory cytokines (IL-10 IL-13) DTA. inflammasome–mediated secretome reduced differentiation migration stem cells. Neutralizing or replenishing accelerated regeneration. Moreover, conditional P2rx7 myeloid cells activation facilitated demonstrates P2X7R/NLRP3 represents promising therapeutic target for repair.

Language: Английский

---

Therapeutic potential of adipose-derived stem cell extracellular vesicles: from inflammation regulation to tissue repair

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 7, 2024

Inflammation is a key pathological feature of many diseases, disrupting normal tissue structure and resulting in irreversible damage. Despite the need for effective inflammation control, current treatments, including stem cell therapies, remain insufficient. Recently, extracellular vesicles secreted by adipose-derived cells (ADSC-EVs) have garnered attention their significant anti-inflammatory properties. As carriers bioactive substances, these demonstrated potent capabilities modulating promoting repair conditions such as rheumatoid arthritis, osteoarthritis, diabetes, cardiovascular stroke, wound healing. Consequently, ADSC-EVs are emerging promising alternatives to conventional ADSC-based offering advantages reduced risk immune rejection, enhanced stability, ease storage handling. However, specific mechanisms which regulate under not fully understood. This review discusses role impact on disease prognosis, potential promote repair. Additionally, it provides insights into future clinical research focused ADSC-EV therapies inflammatory overcome some limitations associated with cell-based therapies.

Language: Английский

---