PDF(Pubmed)
Abstract：
Satisfactory healing following acute tendon injury is marred by fibrosis. Despite the high frequency of tendon injuries and poor outcomes, there are no pharmacological therapies in use to enhance the healing process. Moreover, systemic treatments demonstrate poor tendon homing, limiting the beneficial effects of potential tendon therapeutics. To address this unmet need, we leveraged our existing tendon healing spatial transcriptomics dataset and identified an area enriched for expression of Acp5 (TRAP) and subsequently demonstrated robust TRAP activity in the healing tendon. This unexpected finding allowed us to refine and apply our existing TRAP binding peptide (TBP) functionalized nanoparticle (NP) drug delivery system (DDS) to facilitate improved delivery of systemic treatments to the healing tendon. To demonstrate the translational potential of this DDS, we delivered niclosamide (NEN), an S100a4 inhibitor. While systemic delivery of free NEN did not alter healing, TBP-NPNEN enhanced both functional and mechanical recovery, demonstrating the translational potential of this approach to enhance the tendon healing process.
摘要：
急性肌腱损伤后令人满意的愈合受到纤维化的损害。尽管肌腱损伤的频率很高，结果很差，没有使用药物疗法来增强愈合过程。此外，全身治疗显示肌腱归巢不良，限制潜在肌腱疗法的有益效果。为了解决这个未满足的需求，我们利用我们现有的肌腱愈合空间转录组学数据集,确定了一个富含Acp5(TRAP)表达的区域,随后在愈合的肌腱中显示出稳健的TRAP活性.这一出乎意料的发现使我们能够改进和应用我们现有的TRAP结合肽(TBP)官能化纳米颗粒(NP)药物递送系统(DDS),以促进改善向愈合肌腱的全身治疗的递送。为了证明该DDS的翻译潜力，我们交付了氯硝柳胺(NEN)，S100a4抑制剂。虽然全身递送游离NEN并没有改变愈合，TBP-NPNEN增强了功能和机械恢复，证明了这种方法的平移潜力，以增强肌腱愈合过程。
