Cocktail-like gradient gelatin/hyaluronic acid bioimplant for enhancing tendon-bone healing in fatty-infiltrated rotator cuff injury models

The regeneration of enthesis tissue (native tendon-bone interface) at the post-surgically repaired rotator cuff remains a challenge for clinicians, especially with the emergence of degenerative affection such as fatty infiltration that exacerbate poor tendon-bone healing. In this study, we proposed a cocktail-like hydrogel with a four-layer structure (BMSCs+gNC@GH) for enhancing fatty infiltrated tendon-bone healing. As collagen and hyaluronic acid are the main biomacromolecules that constitute the extracellular matrix of enthesis tissue, this hydrogel was composed of UV-curable gelatin/hyaluronic acid (GelMA/HAMA) dual network gel (GH) with nanoclay (NC) and stem cells loaded. The results showed that NC exhibited a cocktail-like gradient distribution in GH, which effectively mimicked the structure of native enthesis and supported the long-term culture and encapsulation of BMSCs. What's more, the gradient variation of NC provided a biological signal for promoting gradient osteogenic differentiation of cells. Based on the in vivo results, BMSCs+gNC@GH effectively promoted fibrocartilage layer regeneration at the tendon-bone interface and inhibited fatty infiltration. Therefore, BMSCs+gNC@GH group exhibited better biomechanical properties. Thus, this cocktail-like implant may be a promising tissue-engineered scaffold for tendon-bone healing, and it provides a new idea for the development of scaffolds with the function of inhibiting degeneration.