A significant clinical challenge in large-to-massive rotator cuff tendon injuries is the need for sustaining high mechanical demands despite limited tissue regeneration, which often results in clinical repair failure with high retear rates and long-term functional deficiencies. To address this, an innovative tendon substitute named “BioTenoForce” is engineered, which uses (i) tendon extracellular matrix (tECM)'s rich biocomplexity for tendon-specific regeneration and (ii) a mechanically robust, slow degradation polyurethane elastomer to mimic native tendon's physical attributes for sustaining long-term shoulder movement. Comprehensive assessments revealed outstanding performance of BioTenoForce, characterized by robust core-shell interfacial bonding, human rotator cuff tendon-like mechanical properties, excellent suture retention, biocompatibility, and tendon differentiation of human adipose-derived stem cells. Importantly, BioTenoForce, when used as an interpositional tendon substitute, demonstrated successful integration with regenerative tissue, exhibiting remarkable efficacy in repairing large-to-massive tendon injuries in two animal models. Noteworthy outcomes include durable repair and sustained functionality with no observed breakage/rupture, accelerated recovery of rat gait performance, and >1 cm rabbit tendon regeneration with native tendon-like biomechanical attributes. The regenerated tissues showed tendon-like, wavy, aligned matrix structure, which starkly contrasts with the typical disorganized scar tissue observed after tendon injury, and was strongly correlated with tissue stiffness. Our simple yet versatile approach offers a dual-pronged, broadly applicable strategy that overcomes the limitations of poor regeneration and stringent biomechanical requirements, particularly essential for substantial defects in tendon and other load-bearing tissues.

中文翻译：

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设计细胞外基质功能化的承重肌腱替代品，以有效修复大面积肌腱缺损

大面积肩袖肌腱损伤的一个重大临床挑战是​​，尽管组织再生有限，但仍需要维持高机械需求，这通常会导致临床修复失败、高延迟率和长期功能缺陷。为了解决这个问题，设计了一种名为“BioTenoForce”的创新肌腱替代品，它使用（i）肌腱细胞外基质（tECM）丰富的生物复杂性进行肌腱特异性再生，以及（ii）机械坚固、缓慢降解的聚氨酯弹性体来模仿天然肌腱肌腱维持长期肩部运动的物理属性。综合评估显示 BioTenoForce 具有出色的性能，其特点是强大的核壳界面粘合、人类肩袖腱样机械性能、出色的缝合线保留、生物相容性以及人类脂肪干细胞的肌腱分化。重要的是，当 BioTenoForce 用作间置肌腱替代品时，它证明了与再生组织的成功整合，在两种动物模型中显示出修复大面积肌腱损伤的显着功效。值得注意的结果包括持久修复和持续功能，没有观察到断裂/断裂，大鼠步态性能的加速恢复，以及具有天然肌腱样生物力学属性的 >1 厘米兔肌腱再生。再生组织呈现肌腱状、波状、对齐的基质结构，这与肌腱损伤后观察到的典型杂乱疤痕组织形成鲜明对比，并且与组织硬度密切相关。我们简单而通用的方法提供了一种双管齐下、广泛适用的策略，克服了再生不良和严格的生物力学要求的局限性，这对于肌腱和其他承重组织的严重缺陷尤其重要。