Tendon and Bone Healing: Integrating Physiology, Autografts, and Regenerative Strategies

Tendon injuries remain a major clinical challenge due to the limited regenerative capacity of tendon tissue and its strong tendency to heal through fibrotic scar formation rather than functional restoration. Although tendons appear structurally simple, their hierarchical organization, cellular heterogeneity, and tightly regulated healing phases reveal a complex biological system that is highly sensitive to mechanical and molecular disturbances. Following injury, an exaggerated inflammatory response and disorganized extracellular matrix deposition often shift the healing process toward fibrosis, impairing mechanical performance and reducing tissue mobility.

Recent advances in bioengineering have introduced scaffold-based and exosome-based strategies as promising approaches to improve tendon healing outcomes. Scaffold technologies, including three-dimensional and four-dimensional bioprinting, aim to restore mechanical integrity and guide cellular alignment, particularly in chronic or structurally compromised tendons. In parallel, exosome-based therapies have gained attention for their ability to modulate inflammation, promote angiogenesis, and regulate cellular behavior without the need for invasive surgical intervention. Despite their individual advantages, neither approach alone has consistently achieved scarless tendon regeneration.

This review integrates current knowledge on tendon physiology, injury mechanisms, and healing dynamics with emerging bioengineering strategies. Particular emphasis is placed on the complementary roles of biomaterial scaffolds and exosome-based therapies, highlighting their potential synergistic effect in promoting regenerative, rather than fibrotic, healing. Understanding how these approaches can be strategically combined may represent a critical step toward achieving functional and scar-minimized tendon repair.