关键词: HUVECs-exos Inflammation Macrophage polarization TDSCs Tendon healing

Mesh : Animals Exosomes / metabolism Hydrogels / chemistry pharmacology Rats Humans Human Umbilical Vein Endothelial Cells Achilles Tendon / injuries Tendon Injuries / therapy Regeneration Wound Healing / drug effects Male Rats, Sprague-Dawley Anti-Inflammatory Agents / pharmacology chemistry Tissue Engineering / methods Tissue Scaffolds / chemistry Inflammation

来  源:   DOI:10.1186/s12951-024-02607-0   PDF(Pubmed)

Abstract:
Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially in cases like the Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to the inherent low metabolic activity and vascularization of tendon tissue. As pressing is needed for effective interventions, efforts are made to explore biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, an injectable hydrogel amalgamated with human umbilical vein endothelial cells-derived exosomes (HUVECs-Exos) was prepared and named H-Exos-gel in this study, aiming to enhance tendon repair. In our research involving a model of Achilles tendon injuries in 60 rats, we investigated the efficacy of H-Exos-gel through histological assessments performed at 2 and 4 weeks and behavioral assessments conducted at the 4-week mark revealed its ability to enhance the Achilles tendon\'s mechanical strength, regulate inflammation and facilitate tendon regeneration and functional recovery. Mechanically, the H-Exos-gel modulated the cellular behaviors of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the H-Exos-gel epitomizes a viable bioactive medium for tendon healing, heralding a promising avenue for the clinical amelioration of tendon injuries.
摘要:
肌腱损伤是常见的骨科疾病,具有挑战性的愈合轨迹,尤其是在跟腱病痛的情况下。肌腱损伤的愈合轨迹往往是次优的,由于肌腱组织固有的低代谢活性和血管形成,导致瘢痕形成和功能损害。由于迫切需要有效的干预措施,努力探索生物材料以增强肌腱愈合。然而,组织工程方法在优化组织支架和纳米医学策略方面面临障碍。为了驾驭这些挑战,在这项研究中,制备了一种与人脐静脉内皮细胞衍生的外泌体(HUVECs-Exos)混合的可注射水凝胶,并命名为H-Exos-gel。旨在增强肌腱修复。在我们涉及60只大鼠跟腱损伤模型的研究中,我们通过在2周和4周进行的组织学评估来研究H-Exos-gel的功效,在4周进行的行为评估显示其增强跟腱机械强度的能力,调节炎症,促进肌腱再生和功能恢复。机械上,H-Exos-gel通过抑制炎症相关途径和促进增殖相关途径来调节巨噬细胞和肌腱源性干细胞(TDSC)的细胞行为。我们的发现描述了H-Exos-gel是肌腱愈合的可行生物活性介质,预示着临床上改善肌腱损伤的有希望的途径。
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