Design and fabrication of decellularized heterotopic ossification tendon-derived scaffold to enhance tendon-to-bone integration

Injuries at the tendon-bone interface are common in sports medicine and can greatly affect a patient's quality of life. Healing at this interface is slow and challenging because it involves the repair of two different types of tissue. This study aims to develop a decellularized heterotopic ossification tendon-derived scaffold (dHOTDS) to serve as a bridge between tendon and bone, promoting faster integration. The dHOTDS is prepared using a combination of physical, chemical, and enzymatic treatments, including Triton X-100, sodium dodecyl sulfate, and trypsin. This approach effectively removes cellular components while preserving the native extracellular matrix structure. The resulting heterotopic ossification structure closely resembles normal bone tissue. In vitro experiments showed that the ‌dHOTDS significantly enhances mesenchymal stem cell differentiation by upregulating both osteogenic and chondrogenic gene expression. In vivo application at the Achilles tendon-calcaneus interface demonstrated that dHOTDS implantation improves mechanical strength and stimulates cartilage tissue formation during tendon-bone healing. Overall, the dHOTDS represents a novel regenerative biomaterial with promising potential, providing an innovative strategy and theoretical basis for improving tendon-to-bone healing outcomes.