In the realm of sports medicine, injuries involving the tendon–bone interface, particularly those affecting the rotator cuff and anterior cruciate ligament (ACL), remain a significant clinical challenge. These injuries often necessitate reconstructive surgery to restore function and alleviate pain. However, the success of such surgical interventions hinges largely on the effectiveness of tendon–bone healing, a complex biological process where the tendon graft must firmly integrate into the bone tunnel. Recent advances in bioengineering have paved the way for innovative strategies aimed at enhancing this crucial healing phase, offering hope for improved patient outcomes and faster recovery times.
Tendon–bone insertion sites represent a unique anatomical and biomechanical junction, where the soft, fibrous tendon transitions into hard, mineralized bone. This gradient in tissue properties complicates regenerative efforts, as effective healing requires re-establishing a seamless interface capable of withstanding mechanical loads. Conventional surgical approaches often fall short due to poor graft integration and the risk of failure or re-injury. To address these limitations, researchers have turned to tissue engineering and regenerative medicine techniques, focusing on biological augmentation to accelerate and optimize the tendon–bone healing cascade.
One prominent area of exploration involves the use of bioengineered scaffolds. These scaffolds act as three-dimensional frameworks that mimic the native extracellular matrix, providing structural support and guiding cell proliferation and differentiation at the injury site. Advances in biomaterials science have led to the development of scaffolds composed of biocompatible polymers, ceramics, and composites that degrade at controlled rates, thereby allowing gradual load transfer and reducing long-term foreign body reactions. By tailoring the scaffold’s architecture and biochemical cues, scientists aim to create an environment conducive to robust tendon–bone integration.
Hydrogels represent another cutting-edge biomaterial in this domain. Their high water content and viscoelastic properties closely resemble natural matrix environments, facilitating nutrient diffusion and cellular migration. When engineered with bioactive molecules such as growth factors or stem cells, hydrogels can actively modulate the local healing milieu. This biofunctionalization enhances signaling pathways that promote osteogenesis and tenogenesis, critical processes underpinning tendon–bone repair. Moreover, injectable hydrogel formulations offer minimally invasive delivery options, thereby reducing surgical trauma and enhancing patient compliance.
Beyond biomaterials, biological augmentation strategies including the application of growth factors and cytokines have garnered attention. These signaling molecules serve as potent chemoattractants and mitogens, orchestrating the recruitment, proliferation, and differentiation of progenitor cells at the repair site. However, the transient nature and rapid degradation of these proteins in vivo pose challenges for sustained therapeutic efficacy. To overcome these hurdles, researchers are exploring controlled release systems integrated within scaffolds or hydrogels, enabling prolonged local delivery and enhanced bioavailability.
Additionally, the transplantation of locally differentiated cells derived from various sources represents a promising approach. Mesenchymal stem cells (MSCs), capable of differentiating into osteoblasts and tenocytes, have been extensively studied for their regenerative potential. When seeded onto biomaterial scaffolds or encapsulated within hydrogels, these cells can directly contribute to tissue regeneration while secreting paracrine factors that modulate inflammation and recruit endogenous repair mechanisms. Despite encouraging preclinical results, challenges remain in standardizing cell isolation, expansion, and delivery protocols to achieve consistent clinical outcomes.
Recognizing the limitations of monotherapies, contemporary research increasingly focuses on combinatorial approaches that synergize multiple bioengineering strategies. Integrating scaffolds with controlled release of growth factors and cellular therapies holds the potential to address the multifaceted nature of tendon–bone healing. Such integrated platforms can recreate the native tissue microenvironment more faithfully, promoting spatial and temporal coordination of biological cues essential for effective repair.
A comprehensive review of current literature reveals that most advancements have centered around biomaterials as the foundational element upon which other therapies are layered. Bioabsorbable interference screws, for instance, not only provide mechanical fixation but can also serve as vehicles for delivering bioactive substances at the bone tunnel interface. The optimization of these devices to enhance biodegradability and bioactivity is a critical area of ongoing research, aiming to eliminate the need for hardware removal surgeries and reduce complications.
Despite significant progress, several barriers impede the translation of bioengineering innovations into clinical practice. Heterogeneity in injury types, patient-specific factors, and surgical techniques contribute to variable healing outcomes. Moreover, the complex biology of the tendon–bone interface, involving inflammatory responses, extracellular matrix remodeling, and biomechanical loading, necessitates multifactorial therapeutic interventions. Future research must therefore prioritize understanding the interplay of these factors to tailor personalized regenerative therapies.
Emerging technologies such as 3D bioprinting and gene editing hold promise for revolutionizing tendon–bone repair strategies. Bioprinting enables the precise fabrication of scaffolds with controlled microarchitecture and spatial distribution of multiple cell types, closely mimicking native tissue organization. Gene editing tools may enhance the regenerative capacity of implanted cells by modulating key signaling pathways involved in differentiation and matrix synthesis. Integrating these technologies with existing biomaterial platforms could usher in a new era of highly effective and customizable tendon–bone healing therapies.
In conclusion, the application and optimization of bioengineering strategies in facilitating tendon–bone healing represent a dynamic and rapidly evolving field. By combining biomaterial scaffolds, bioactive molecules, and cellular therapies, researchers are developing sophisticated platforms that address the inherent challenges of soft tissue to bone integration. The ongoing elucidation of molecular and biomechanical mechanisms underlying tendon–bone repair, coupled with technological innovations, positions this field at the forefront of regenerative medicine with profound implications for sports medicine and orthopedic surgery.
As this multidisciplinary research continues to gain momentum, the translation of laboratory findings into safe, effective, and widely accessible clinical interventions remains a priority. With sustained investment and collaboration among bioengineers, clinicians, and materials scientists, the goal of restoring full function and durability to injured tendon–bone interfaces may soon become a standard reality in patient care.
—
Subject of Research: Bioengineering strategies for enhancing tendon–bone healing after reconstructive surgery
Article Title: Application and optimization of bioengineering strategies in facilitating tendon–bone healing
Article References: Yang, C., Chen, C., Chen, R. et al. Application and optimization of bioengineering strategies in facilitating tendon–bone healing. BioMed Eng OnLine 24, 46 (2025). https://doi.org/10.1186/s12938-025-01368-7
Image Credits: AI Generated
DOI: https://doi.org/10.1186/s12938-025-01368-7
