Hou Jingyi, Yang Rui, Vuong Ivan, Li Fangqi, Kong Jiayuan, Mao Hai-Quan
Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University,107# Yan Jiang Road West, Guangzhou, Guangdong, 510120, PR China.
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore MD 21205, USA.
Acta Biomater. 2021 Aug;130:1-16. doi: 10.1016/j.actbio.2021.05.043. Epub 2021 May 31.
Adult tendon tissue demonstrates a limited regenerative capacity, and the natural repair process leaves fibrotic scar tissue with inferior mechanical properties. Surgical treatment is insufficient to provide the mechanical, structural, and biochemical environment necessary to restore functional tissue. While numerous strategies including biodegradable scaffolds, bioactive factor delivery, and cell-based therapies have been investigated, most studies have focused exclusively on either suppressing inflammation or promoting tenogenesis, which includes tenocyte proliferation, ECM production, and tissue formation. New biomaterials-based approaches represent an opportunity to more effectively balance the two processes and improve regenerative outcomes from tendon injuries. Biomaterials applications that have been explored for tendon regeneration include formation of biodegradable scaffolds presenting topographical, mechanical, and/or immunomodulatory cues conducive to tendon repair; delivery of immunomodulatory or tenogenic biomolecules; and delivery of therapeutic cells such as tenocytes and stem cells. In this review, we provide the biological context for the challenges in tendon repair, discuss biomaterials approaches to modulate the immune and regenerative environment during the healing process, and consider the future development of comprehensive biomaterials-based strategies that can better restore the function of injured tendon. STATEMENT OF SIGNIFICANCE: Current strategies for tendon repair focus on suppressing inflammation or enhancing tenogenesis. Evidence indicates that regulated inflammation is beneficial to tendon healing and that excessive tissue remodeling can cause fibrosis. Thus, it is necessary to adopt an approach that balances the benefits of regulated inflammation and tenogenesis. By reviewing potential treatments involving biodegradable scaffolds, biological cues, and therapeutic cells, we contrast how each strategy promotes or suppresses specific repair steps to improve the healing outcome, and highlight the advantages of a comprehensive approach that facilitates the clearance of necrotic tissue and recruitment of cells during the inflammatory stage, followed by ECM synthesis and organization in the proliferative and remodeling stages with the goal of restoring function to the tendon.
成人肌腱组织的再生能力有限，其自然修复过程会留下机械性能较差的纤维化瘢痕组织。手术治疗不足以提供恢复功能性组织所需的机械、结构和生化环境。尽管已经研究了多种策略，包括可生物降解支架、生物活性因子递送和基于细胞的疗法，但大多数研究都只专注于抑制炎症或促进腱形成，腱形成包括肌腱细胞增殖、细胞外基质产生和组织形成。基于新型生物材料的方法为更有效地平衡这两个过程并改善肌腱损伤的再生结果提供了契机。已探索用于肌腱再生的生物材料应用包括形成具有有利于肌腱修复的拓扑、机械和/或免疫调节线索的可生物降解支架；递送免疫调节或腱形成生物分子；以及递送治疗性细胞，如肌腱细胞和干细胞。在本综述中，我们阐述了肌腱修复挑战的生物学背景，讨论了在愈合过程中调节免疫和再生环境的生物材料方法，并考虑了基于生物材料的综合策略的未来发展，这些策略可以更好地恢复受损肌腱的功能。重要性声明：目前的肌腱修复策略侧重于抑制炎症或增强腱形成。有证据表明，适度的炎症对肌腱愈合有益，而过度的组织重塑会导致纤维化。因此，有必要采取一种平衡适度炎症和腱形成益处的方法。通过回顾涉及可生物降解支架、生物线索和治疗性细胞的潜在治疗方法，我们对比了每种策略如何促进或抑制特定的修复步骤以改善愈合结果，并强调了一种综合方法的优势，该方法有助于在炎症阶段清除坏死组织并募集细胞，随后在增殖和重塑阶段进行细胞外基质的合成和组织，目标是恢复肌腱的功能。
