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用于前交叉韧带重建中无瘢痕愈合的免疫调节涂层

Immunoregulative coating for scarless healing in anterior cruciate ligament reconstruction.

作者信息

Wang Shuang, Xu Chao, Yu Yuanman, Li Jie, Chen Tianwu, Wang Jing, Liu Changsheng

机构信息

Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Center for Biomedical Materials of the Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China.

College of Materials Science and Engineering, Wuhan Textile University, Wuhan, 430200, PR China.

出版信息

Bioact Mater. 2024 Nov 15;45:71-87. doi: 10.1016/j.bioactmat.2024.11.007. eCollection 2025 Mar.

Abstract

Polyethylene terephthalate (PET) artificial ligaments are widely used in anterior cruciate ligament (ACL) reconstruction due to their high tensile strength. However, bone tunnel enlargement around PET ligaments poses a risk for surgical failure. PET's inert surface, lower bioactivity, and mechanical abrasion trigger an M1 macrophage-mediated inflammatory response, leading to excessive, disorganized scar tissue. This scar tissue creates a space-occupying effect at the interface, obstructing graft-bone integration and contributing to bone tunnel enlargement. To address this issue, we developed a multi-layered immune-regulating hydrogel coating for scar-free PET-bone integration. Comprising gelatin methacrylate (GelMA), polyethyleneglycol diacrylate (PEGDA), and sulfated polysaccharide (SCS), the hydrogel forms a hydrogen-bonded lubricating layer to reduce friction. The sustained release of SCS also down-regulates M1 macrophage polarization, inhibiting early scar formation. By eliminating the space-occupying effect of scar tissue, SCS subsequently promotes M2 macrophage polarization. This shift releases endogenous factors that enhance blood vessel formation and new bone growth, ultimately achieving high-quality graft-bone integration. The application of this multi-layered, inflammation-modulating hydrogel coating not only removes scar tissue barriers but also improves graft-bone integration through enhanced angiogenesis and osteogenesis. Moreover, it avoids the overuse of exogenous growth factors and potential complications, offering a more convenient and feasible therapeutic strategy.

摘要

聚对苯二甲酸乙二酯(PET)人工韧带因其高拉伸强度而广泛应用于前交叉韧带(ACL)重建。然而,PET韧带周围的骨隧道扩大存在手术失败的风险。PET的惰性表面、较低的生物活性和机械磨损会引发M1巨噬细胞介导的炎症反应,导致过度、无序的瘢痕组织形成。这种瘢痕组织在界面处产生占位效应,阻碍移植物与骨的整合,并导致骨隧道扩大。为了解决这个问题,我们开发了一种用于PET与骨无瘢痕整合的多层免疫调节水凝胶涂层。该水凝胶由甲基丙烯酸明胶(GelMA)、聚乙二醇二丙烯酸酯(PEGDA)和硫酸化多糖(SCS)组成,形成氢键润滑层以减少摩擦。SCS的持续释放还下调M1巨噬细胞极化,抑制早期瘢痕形成。通过消除瘢痕组织的占位效应,SCS随后促进M2巨噬细胞极化。这种转变释放内源性因子,增强血管形成和新骨生长,最终实现高质量的移植物与骨整合。这种多层炎症调节水凝胶涂层的应用不仅消除了瘢痕组织屏障,还通过增强血管生成和成骨作用改善了移植物与骨的整合。此外,它避免了外源性生长因子的过度使用和潜在并发症,提供了一种更方便、可行的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9093/11609481/cd375c0c346b/ga1.jpg

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